Sample records for significant lv reverse
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Spinelli, Letizia; Morisco, Carmine; Assante di Panzillo, Emiliano; Izzo, Raffaele; Trimarco, Bruno
2013-04-01
Reverse left ventricular (LV) remodeling (>10 % reduction in LV end-systolic volume) may occur in patients recovering for acute ST-elevation myocardial infarction (STEMI), undergoing percutaneous revascularization of infarct-related coronary artery (PCI). To detect whether LV global torsion obtained by two-dimensional speckle-tracking echocardiography was predictive of reverse LV remodeling, 75 patients with first anterior wall STEMI were studied before (T1) and after PCI (T2) and at 6-month follow-up. Two-year clinical follow-up was also accomplished. LV volumes and both LV sphericity index and conic index were obtained by three-dimensional echocardiography. Reverse remodeling was observed in 25 patients (33 %). By multivariate analysis, independent predictors of reverse LV remodeling were: LV conic index, T2 LV torsion and Δ torsion (difference between T2 and T1 LV torsion expressed as percentage of this latter). According to receiver operating characteristic analysis, 1.34°/cm for T2 LV torsion (sensitivity 88 % and specificity 80 %) and 54 % for Δ torsion (sensitivity 92 % and specificity 82 %) were the optimal cutoff values in predicting reverse LV remodeling. In up to 24 month follow-up, 4 non-fatal re-infarction, 7 hospitalization for heart failure and 4 cardiac deaths occurred. By multivariate Cox analysis, the best variable significantly associated with event-free survival rate was reverse LV remodeling with a hazard ratio = 9.9 (95 % confidence interval, 7.9-31.4, p < 0.01). In conclusion, reverse LV remodeling occurring after anterior wall STEMI is associated with favorable long-term outcome. The improvement of global LV torsion following coronary artery revascularization is the major predictor of reverse LV remodeling.
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St John Sutton, Martin; Linde, Cecilia; Gold, Michael R; Abraham, William T; Ghio, Stefano; Cerkvenik, Jeffrey; Daubert, Jean-Claude
2017-03-01
This study sought to determine the effects of abnormal left ventricular (LV) architecture on cardiac remodeling and clinical outcomes in mild heart failure (HF). Cardiac resynchronization therapy (CRT) is an established treatment for HF that improves survival in part by favorably remodeling LV architecture. LV shape is a dynamic component of LV architecture on which contractile function depends. Transthoracic 2-dimensional echocardiography was used to quantify changes in LV architecture over 5 years of follow-up of patients with mild HF from the REVERSE study. REVERSE was a prospective study of patients with large hearts (LV end-diastolic dimension ≥55 mm), LV ejection fraction <40%, and QRS duration >120 ms randomly assigned to CRT-ON (n = 419) and CRT-OFF (n = 191). CRT-OFF patients were excluded from this analysis. LV dimensions, volumes, mass index, and LV ejection fraction were calculated. LV architecture was assessed using the sphericity index, as follows: (LV end-diastolic volume)/(4/3 × π × r 3 ) × 100%. LV architecture improved over time and demonstrated significant associations between LV shape, age, sex, and echocardiography metrics. Changes in LV architecture were strongly correlated with changes in LV end-systolic volume index and LV end-diastolic volume index (both p < 0.0001). Sphericity index emerged as a predictor of death and HF hospitalization in spite of the low adverse event rate. A decrease in LV end-systolic volume index >15% occurred in more than two-thirds of patients, which indicates considerable reverse remodeling. We demonstrated that change in LV architecture in patients with mild HF with CRT is associated with structural and functional remodeling. Mean LV filling pressure was elevated, and the inability to lower it was an additional predictor of HF hospitalization or death. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Kuperstein, Rafael; Blechman, Ido; Ben Zekry, Sagit; Klempfner, Robert; Freimark, Dov; Arad, Michael
2015-01-01
Functional mitral regurgitation (MR) is a common finding in dilated cardiomyopathy. Left ventricular (LV) reverse remodeling with LV size reduction and improvement in LV function is a well recognized phenomenon. We aimed to evaluate the impact of LV remodeling on the mechanism leading to functional MR. Among 188 patients with non-ischemic dilated cardiomyopathy, 10 patients significantly improved their LV function, reduced LV size and MR severity during follow-up (RRMR). A comparison was made between their baseline and follow-up echocardiographic examinations and to a matched-control group of patients who did not improve (no RRMR). LV and left atrium (LA) dimensions and volumes, LV mass (LVM), LV ejection fraction (LVEF) (Simpsons), sphericity index (SI), mitral valve tenting area (TA) coaptation distance (CD), effective regurgitant orifice (ERO), and regurgitant volume were calculated. Multivariable analysis was performed in order to evaluate which echocardiographic parameters related to MR improvement in reverse remodeling. LV and LA dimensions and volumes, LVM, SI, TA, CD, ERO and right ventricle, in the RRMR group significantly decreased at follow-up (p < 0.04 for all). When compared to no RRMR, despite a similar ERO (0.2 ± 0.05 vs. 0.2 ± 0.08, p = 0.13) and a larger regurgitant volume (38 ± 9 vs. 29 ± 8 mL, p = 0.05) and despite similar clinical characteristics and medical treatment we found significantly higher LVEF, smaller LV dimensions and volumes, smaller LVM and SI in the RRMR group (p < 0.05 for all). On multivariable analysis the SI was the sole predictor of RRMR (p = 0.04, OR = 0.76, CI 0.58-0.99). Reverse remodeling characterized by improvement in LV function, reduction in LV size and an associated reduction in MR severity is related to LV SI at baseline.
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St John Sutton, Martin; Plappert, Ted; Adamson, Philip B; Li, Pei; Christman, Shelly A; Chung, Eugene S; Curtis, Anne B
2015-05-01
Biventricular pacing in heart failure (HF) improves survival, relieves symptoms, and attenuates left ventricular (LV) remodeling. However, little is known about biventricular pacing in HF patients with atrioventricular block because they are typically excluded from biventricular trials. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial randomized patients with atrioventricular block, New York Heart Association symptom classes I to III HF, and LV ejection fraction ≤50% to biventricular or right ventricular pacing. Doppler echocardiograms were obtained at randomization (after 30 to 60 days of right ventricular pacing postimplant) and every 6 months through 24 months. Data analysis comparing changes in 10 prespecified echo parameters over time was conducted using a Bayesian design. LV end systolic volume index was also evaluated as a predictor of mortality/morbidity. Of 691 randomized subjects, 624 had paired Doppler echocardiogram data for ≥1 analyses at 6, 12, 18, or 24 months. Biventricular pacing significantly reduced LV volume indices and intraventricular mechanical delay, and improved LV ejection fraction, consistent with LV reverse remodeling. These parameters showed little change with right ventricular pacing alone, indicating no systematic reverse remodeling with right ventricular pacing. LV end systolic volume index was predictive of mortality/morbidity; the estimated risk increased up to 1% for every 1 mL/m(2) increase in LV end systolic volume index. LV end systolic volume index is a significant predictor of mortality/morbidity in this population. Cardiac structure and function are improved with biventricular pacing for patients with atrioventricular block and LV systolic dysfunction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00267098. © 2015 American Heart Association, Inc.
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2012-01-01
Left ventricular (LV) dysfunction and dilated cardiomyopathy (DCM) are rarely attributable to sustained or incessant tachyarrhythmias in infants and children with Wolff-Parkinson-White (WPW) syndrome. However, several recent reports suggested that significant LV dysfunction may develop in WPW syndrome in the absence of tachyarrhythmias. It is assumed that an asynchronous ventricular activation over the accessory pathway, especially right-sided, induces septal wall motion abnormalities, ventricular remodeling and ventricular dysfunction. The prognosis of DCM associated with asymptomatic WPW is excellent. Loss of ventricular pre-excitation results in mechanical resynchronization and reverse remodeling where LV function recovers completely. The reversible nature of LV dysfunction after loss of ventricular pre-excitation supports the causal relationship between LV dysfunction and ventricular pre-excitation. This review summarizes recent clinical and electrophysiological evidence for development of LV dysfunction or DCM in asymptomatic WPW syndrome, and discusses the underlying pathophysiological mechanism. PMID:23323117
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Schultz, Sharon J; Zhang, Miaohua; Champoux, James J
2010-03-19
The RNase H activity of reverse transcriptase is required during retroviral replication and represents a potential target in antiviral drug therapies. Sequence features flanking a cleavage site influence the three types of retroviral RNase H activity: internal, DNA 3'-end-directed, and RNA 5'-end-directed. Using the reverse transcriptases of HIV-1 (human immunodeficiency virus type 1) and Moloney murine leukemia virus (M-MuLV), we evaluated how individual base preferences at a cleavage site direct retroviral RNase H specificity. Strong test cleavage sites (designated as between nucleotide positions -1 and +1) for the HIV-1 and M-MuLV enzymes were introduced into model hybrid substrates designed to assay internal or DNA 3'-end-directed cleavage, and base substitutions were tested at specific nucleotide positions. For internal cleavage, positions +1, -2, -4, -5, -10, and -14 for HIV-1 and positions +1, -2, -6, and -7 for M-MuLV significantly affected RNase H cleavage efficiency, while positions -7 and -12 for HIV-1 and positions -4, -9, and -11 for M-MuLV had more modest effects. DNA 3'-end-directed cleavage was influenced substantially by positions +1, -2, -4, and -5 for HIV-1 and positions +1, -2, -6, and -7 for M-MuLV. Cleavage-site distance from the recessed end did not affect sequence preferences for M-MuLV reverse transcriptase. Based on the identified sequence preferences, a cleavage site recognized by both HIV-1 and M-MuLV enzymes was introduced into a sequence that was otherwise resistant to RNase H. The isolated RNase H domain of M-MuLV reverse transcriptase retained sequence preferences at positions +1 and -2 despite prolific cleavage in the absence of the polymerase domain. The sequence preferences of retroviral RNase H likely reflect structural features in the substrate that favor cleavage and represent a novel specificity determinant to consider in drug design. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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Kuppahally, Suman S; Fowler, Michael B; Vagelos, Randall; Wang, Paul; Al-Ahmad, Amin; Paloma, Allan; Liang, David
2009-08-01
Responders to cardiac resynchronization therapy (CRT) have greater left ventricular (LV) dyssynchrony than nonresponders prior to CRT. We conducted this study to see whether the long term responders have more worsening of LV dyssynchrony and LV function on acute interruption of CRT. We identified 22 responders and 13 nonresponders who received CRT as per standard criteria for 23.73 +/- 7.9 months (median 24.5 months). We assessed the acute change in LV function, mitral regurgitation (MR) and compared LV dyssynchrony in CRT on and off modes. On turning off CRT, there was no significant worsening of LV dyssynchrony in both responders and nonresponders. The dyssynchrony measurements by SPWMD, TDI and 3D echocardiography did not correlate significantly. LVESV increased (p = 0.02) and MR (p = 0.01) worsened in CRT-off mode in responders only without significant change in LVEF or LV dimensions. In long-term responders to CRT, there is alteration in the function of remodeled LV with acute interruption of CRT, without significant worsening of LV dyssynchrony. The role of different echocardiographic parameters in the assessment of LV dyssynchrony remains controversial. Even after long-term CRT reversely remodels the LV, the therapy needs to be continued uninterrupted for sustained benefits.
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NASA Astrophysics Data System (ADS)
Xie, Shijun; Li, Fuhua; Zhang, Xiaojun; Zhang, Jiquan; Xiang, Jianhai
2017-11-01
The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus (WSSV) in shrimp. In this study, the nucleotide sequence encoding peritrophin-like protein of Litopenaeus vannamei (LvPT) was amplified from a yeast two-hybrid library of L. vannamei. The epitope peptide of LvPT was predicted with the GenScript OptimumAntigen™ design tool. An anti-LvPT polyclonal antibody was produced and shown to specifically bind a band at 27 kDa, identified as LvPT. The LvPT protein was expressed and its concentration determined. LvPT dsRNA (4 μg per shrimp) was used to inhibit LvPT expression in shrimp, and a WSSV challenge experiment was then performed with reverse gavage. The pleopods, stomachs, and guts were collected from the shrimp at 0, 24, 48, and 72 h post-infection (hpi). Viral load quantification showed that the levels of WSSV were significantly lower in the pleopods, stomachs, and guts of shrimp after LvPT dsRNA interference than in those of the controls at 48 and 72 hpi. Our results imply that LvPT plays an important role during WSSV infection of the digestive tract.
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Totaro, Pasquale; Adragna, Nicola; Argano, Vincenzo
2008-03-01
Today, the 'gold standard' treatment of functional mitral regurgitation (MR) is the subject of much discussion. Although restrictive annuloplasty is currently considered the most reproducible technique, the means by which the degree of annular restriction is optimized remains problematic. The study was designed in order to identify whether the degree of restriction of the mitral annulus could influence early and midterm results following the treatment of functional MR using restrictive annuloplasty. A total of 32 consecutive patients with functional MR grade > or = 3+ was enrolled, among whom the mean anterior-posterior (AP) mitral annulus diameter was 39 +/- 3 mm. Restrictive mitral annuloplasty (combined with coronary artery bypass grafting) was performed in all patients using a Carpentier-Edwards Classic or Physio ring (size 26 or 28). The degree of AP annular restriction was calculated for each patient, and correlated with early and mid-term residual MR and left ventricular (LV) reverse remodeling (in terms of LV end-diastolic diameter (LVEDD) and LV end-diastolic volume (LVEDV) reduction). All surviving patients were examined at a one-year follow up. The mean AP mitral annulus restriction achieved was 48 +/- 4%. Intraoperatively, transesophageal echocardiography showed no residual MR in any patient. Before discharge from hospital, transthoracic echocardiography confirmed an absence of residual MR and showed significant LV reverse remodeling (LVEDV from 121 +/- 25 ml to 97 +/- 26 ml; LVEDD from 55 +/- 6 mm to 47 +/- 8 mm). A significant correlation (r = 0.57, p < 0.001) was identified between the degree of AP annulus restriction and LVEDV reduction. A cut-off of annular restriction of 40% (based on AP annulus measurement) correlated with a more significant reverse remodeling. The early postoperative data, with no recurrence of significant MR, was confirmed at a one-year follow up examination. A marked restriction of the AP mitral annulus diameter (> 40% of preoperative) appears to have a favorable influence on early postoperative LV reverse remodeling, and also allows for complete resolution of functional MR. In addition, 'no tolerance' of early residual MR seems to have a favorable influence on mid-term results, leading to a reduction in the one-year recurrence of significant MR.
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Paulis, L; Matuskova, J; Adamcova, M; Pelouch, V; Simko, J; Krajcirovicova, K; Potacova, A; Hulin, I; Janega, P; Pechanova, O; Simko, F
2008-09-01
We investigated, whether the substrate for nitric oxide (NO) formation -L-arginine - and the aldosterone receptor antagonist - spironolactone - are able to reverse alterations of the left ventricle (LV) and aorta in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Six groups of male adult Wistar rats were investigated: controls after 4 and 7 weeks of experiment, rats treated with L-NAME for 4 weeks and three recovery groups: spontaneous-reversion (4 weeks L-NAME + 3 weeks placebo), spironolactone-induced reversion (4 weeks L-NAME + 3 weeks spironolactone) and L-arginine-induced reversion (4 weeks L-NAME+ 3 weeks L-arginine). Blood pressure was measured by tail-cuff plethysmography. Relative weight of the LV, myocardial fibrosis (based upon histomorphometry and hydroxyproline determination) and conjugated dienes in the LV and aortic cross-sectional area, inner diameter and wall thickness were determined. NO-synthase activity was investigated in the LV and aorta. L-NAME administration induced hypertension, left ventricular hypertrophy (LVH), LV fibrosis, aortic thickening and diminution of NO-synthase activity in the LV and aorta. Reduction in blood pressure and regression of LVH were observed in all recovery groups, yet reduction in LV fibrosis and aortic thickening were not. NO-synthase activity was restored only in the L-arginine and spironolactone group. In our study, the reversion of hypertension and LVH was not dependent on the restoration of NO-synthase activity. Moreover, LV fibrosis and aortic remodelling seem to be more resistant to conditions resulting in regression of LVH. Preserved level of fibrosis in the initial period of LVH regression might result in loss of structural homogeneity and possible functional alterations of the LV.
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Langer, Christoph; Schroeder, Janina; Peterschroeder, Andreas; Vaske, Bernhard; Faber, Lothar; Welge, Dirk; Niethammer, Matthias; Lamp, Barbara; Butz, Thomas; Bitter, Thomas; Oldenburg, Olaf; Horstkotte, Dieter
2010-07-01
Multi-slice computed tomography (MSCT) was proved to provide precise cardiac volumetric assessment. Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with heart failure and reduced ejection fraction (HFREF). In HFREF patients we investigated the potential of MSCT based wall motion analysis in order to demonstrate CRT-induced reversed remodeling. Besides six patients with normal cardiac pump function serving as control group seven HFREF patients underwent contrast enhanced MSCT before and after CRT. Short cardiac axis views of the left ventricle (LV) in end-diastole (ED) and end-systole (ES) served for planimetry. Pre- and post-CRT MSCT based volumetry was compared with 2D echo. To demonstrate CRT-induced reverse remodeling, MSCT based multi-segment color-coded polar maps were introduced. With regard to the HFREF patients pre-CRT MSCT based volumetry correlated with 2D echo data for LV-EDV (MSCT 278.3+/-75.0mL vs. echo 274.4+/-85.6mL) r=0.380, p=0.401, LV-ESV (MSCT 226.7+/-75.4mL vs. echo 220.1+/-74.0mL) r=0.323, p=0.479 and LV-EF (MSCT 20.2+/-8.8% vs. echo 20.0+/-11.9%) r=0.617, p=0.143. Post-CRT MSCT correlated well with 2D echo: LV-EDV (MSCT 218.9+/-106.4mL vs. echo 188.7+/-93.1mL) r=0.87, p=0.011, LV-ESV (MSCT 145+/-71.5mL vs. echo 125.6+/-78mL) r=0.84, p=0.018 and LV-EF (MSCT 29.6+/-11.3mL vs. echo 38.6+/-14.6mL) r=0.89, p=0.007. There was a significant increase of the mid-ventricular septum in terms of absolute LV wall thickening of the responders (pre 0.9+/-2.1mm vs. post 3.3+/-2.2mm; p<0.0005). MSCT based volumetry involving multi-segment color-coded polar maps offers wall motion analysis to demonstrate CRT-induced reverse remodeling which needs to be further validated. 2010 Elsevier Ltd. All rights reserved.
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Tattiyapong, P; Sirikanchana, K; Surachetpong, W
2018-02-01
Tilapia lake virus (TiLV) is an emerging pathogen associated with high mortalities of wild and farm-raised tilapia in different countries. In this study, a SYBR green-based reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay targeting segment three of the virus was developed to detect and quantify TiLV in clinical samples and experimentally challenged fish. All 30 field samples with clinical signs and history consistent with TiLV infection were positive for TiLV as detected by the developed RT-qPCR method. The RT-qPCR technique provided 100 and 10,000 times more sensitive for virus detection than those offered by the RT-PCR and virus isolation in cell culture methods, respectively. The detection limit of the RT-qPCR method was as low as two viral copies/μl. Moreover, the RT-qPCR technique could be applied for TiLV detection in various fish tissues including gills, liver, brain, heart, anterior kidney and spleen. Significantly, this study delivered an accurate and reliable method for rapid detection of TiLV viruses that facilitates active surveillance programme and disease containment. © 2017 John Wiley & Sons Ltd.
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Photoaffinity labeling of the primer binding domain in murine leukemia virus reverse transcriptase.
Tirumalai, R S; Modak, M J
1991-07-02
We have labeled the primer binding domain of murine leukemia virus reverse transcriptase (MuLV RT) by covalently cross-linking 5' end labeled d(T)8 to MuLV RT, using ultraviolet light energy. The specificity and the functional significance of the primer cross-linking reaction were demonstrated by the fact that (i) other oligomeric primers, tRNAs, and also template-primers readily compete with radiolabeled d(T)8 for the cross-linking reaction, (ii) under similar conditions, the competing primers and template-primer also inhibit the DNA polymerase activity of MuLV RT to a similar extent, (iii) substrate deoxynucleotides have no effect, and (iv) the reaction is sensitive to high ionic strength. In order to identify the primer binding domains/sites in MuLV RT; tryptic digests prepared from the covalently cross-linked MuLV RT and [32P]d(T)8 complexes were resolved on C-18 columns by reverse-phase HPLC. Three distinct radiolabeled peptides were found to contain the majority of the bound primer. Of these, peptide I contained approximately 65% radioactivity, while the remainder was associated with peptides II and III. Amino acid composition and sequence analyses of the individual peptides revealed that peptide I spans amino acid residues 72-80 in the primary amino acid sequence of MuLV RT and is located in the polymerase domain. The primer cross-linking site appears to be at or near Pro-76. Peptides II and III span amino acid residues 602-609 and 615-622, respectively, and are located in the RNase H domain. The probable cross-linking sites in peptides II and III are suggested to be at or near Leu-604 and Leu-618, respectively.
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Kembou Tsofack, Japhette Esther; Zamostiano, Rachel; Watted, Salsabeel; Berkowitz, Asaf; Rosenbluth, Ezra; Mishra, Nischay; Briese, Thomas; Lipkin, W. Ian; Kabuusu, Richard M.; Ferguson, Hugh; del Pozo, Jorge
2016-01-01
ABSTRACT Tilapia are an important group of farmed fish that serve as a significant protein source worldwide. In recent years, substantial mortality of wild tilapia has been observed in the Sea of Galilee and in commercial ponds in Israel and Ecuador. We have identified the etiological agent of these mass die-offs as a novel orthomyxo-like virus and named it tilapia lake virus (TiLV). Here, we provide the conditions for efficient isolation, culturing, and quantification of the virus, including the use of susceptible fish cell lines. Moreover, we describe a sensitive nested reverse transcription-PCR (RT-PCR) assay allowing the rapid detection of TiLV in fish organs. This assay revealed, for the first time to our knowledge, the presence of TiLV in diseased Colombian tilapia, indicating a wider distribution of this emerging pathogen and stressing the risk that TiLV poses for the global tilapia industry. Overall, the described procedures should provide the tilapia aquaculture industry with important tools for the detection and containment of this pathogen. PMID:27974544
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Kembou Tsofack, Japhette Esther; Zamostiano, Rachel; Watted, Salsabeel; Berkowitz, Asaf; Rosenbluth, Ezra; Mishra, Nischay; Briese, Thomas; Lipkin, W Ian; Kabuusu, Richard M; Ferguson, Hugh; Del Pozo, Jorge; Eldar, Avi; Bacharach, Eran
2017-03-01
Tilapia are an important group of farmed fish that serve as a significant protein source worldwide. In recent years, substantial mortality of wild tilapia has been observed in the Sea of Galilee and in commercial ponds in Israel and Ecuador. We have identified the etiological agent of these mass die-offs as a novel orthomyxo-like virus and named it tilapia lake virus (TiLV). Here, we provide the conditions for efficient isolation, culturing, and quantification of the virus, including the use of susceptible fish cell lines. Moreover, we describe a sensitive nested reverse transcription-PCR (RT-PCR) assay allowing the rapid detection of TiLV in fish organs. This assay revealed, for the first time to our knowledge, the presence of TiLV in diseased Colombian tilapia, indicating a wider distribution of this emerging pathogen and stressing the risk that TiLV poses for the global tilapia industry. Overall, the described procedures should provide the tilapia aquaculture industry with important tools for the detection and containment of this pathogen. Copyright © 2017 American Society for Microbiology.
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Kubota, Yasuhiko; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Watabe, Hiroshi; Daimon, Takashi; Sakai, Yoshiki; Akita, Toshiaki; Sawa, Yoshiki
2014-03-01
The cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy. Twenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control. At 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05). The combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
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Haroon, Javeria; Foureaux, Giselle; Martins, Almir S; Ferreira, Anderson J; Reis, Adelina M; Javed, Qamar
2015-01-01
This study examined the sex differences for physical, morphological, histological, mRNA, and protein expression levels changes for interleukins and natriuretic peptides in left ventricle (LV) of two groups of adult FVB/N mice; males (WM) and females (WF). LV morphological, histological, reverse transcription and quantitative real-time PCR (RT-PCR), and immunohistochemical (IHC) alterations were determined in FVB/N mice at 34-35 weeks on gender basis. Confirming the gender dimorphism, FVB/N males (WM) illustrated a significant reduction in ANP and IL1-A levels as well as significantly increased body weight (BW (gm)), tibia length (TL (mm)), heart weight (HW (mg)), heart weight-to-body weight (HW/BW (mg/gm)) ratio, heart weight-to-tibia length (HW/TL (mg/mm)) ratio, left ventricle weight (LV (mg)), left ventricle-to-body weight (LV/BW (mg/gm)) ratio, and left ventricle-to-tibia length (LV/TL (mg/mm)) ratio, left ventricular (LV) cardiomyocyte diameter, high BNP, NPRA, IL-1B, and IL1R1 expression in comparison with FVB/N females (WF). Gender differences in relation to left ventricle (LV) may be due to differences in the interleukins and natriuretic peptides levels as an outcome of sex related hormones. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Buss, Sebastian J; Humpert, Per M; Bekeredjian, Raffi; Hardt, Stefan E; Zugck, Christian; Schellberg, Dieter; Bauer, Alexander; Filusch, Arthur; Kuecherer, Helmut; Katus, Hugo A; Korosoglou, Grigorios
2009-05-01
The aim of our study was to investigate whether echocardiographic phase imaging (EPI) can predict response in patients who are considered for cardiac resynchronization therapy (CRT). CRT improves quality of life, exercise capacity, and outcome in patients with bundle-branch block and advanced heart failure. Previous studies used QRS duration to select patients for CRT; the accuracy of this parameter to predict functional recovery, however, is controversial. We examined 42 patients with advanced heart failure (New York Heart Association [NYHA] functional class III to IV, QRS duration >130 ms, and ejection fraction <35%) before and 6 to 8 months after CRT. Left ventricular (LV) dyssynchrony was estimated by calculating the SD of time to peak velocities (Ts-SD) by conventional tissue Doppler imaging (TDI), and the mean phase index (mean EPI-Index) was calculated by EPI in 12 mid-ventricular and basal segments. Patients who were alive and had significant relative decrease in end-systolic LV volume of Delta ESV >or=15% at 6 to 8 months of follow-up were defined as responders. All others were classified as nonresponders. The Ts-SD and the mean EPI-Index were related to Delta ESV (r = 0.43 for Ts-SD and r = 0.67 for mean EPI-Index, p < 0.01 for both), and both parameters yielded similar accuracy for the prediction of LV remodeling (area under the curve of 0.87 for TDI vs. 0.90 for EPI, difference between areas = 0.03, p = NS) and ejection fraction (EF) improvement (area under the curve of 0.87 for TDI vs. 0.93 for EPI, difference between areas = 0.06, p = NS). Furthermore, patients classified as responders by EPI (mean EPI-Index
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Fujimoto, Naoki; Prasad, Anand; Hastings, Jeffrey L.; Arbab-Zadeh, Armin; Bhella, Paul S.; Shibata, Shigeki; Palmer, Dean; Levine, Benjamin D.
2013-01-01
Background Healthy but sedentary aging leads to cardiovascular stiffening, whereas life-long endurance training preserves left ventricular (LV) compliance. However, it is unknown whether exercise training started later in life can reverse the effects of sedentary behavior on the heart. Methods and Results Twelve sedentary seniors and 12 Masters athletes were thoroughly screened for comorbidities. Subjects underwent invasive hemodynamic measurements with pulmonary artery catheterization to define Starling and LV pressure-volume curves; secondary functional outcomes included Doppler echocardiography, magnetic resonance imaging assessment of cardiac morphology, arterial stiffness (total aortic compliance and arterial elastance), and maximal exercise testing. Nine of 12 sedentary seniors (70.6±3 years; 6 male, 3 female) completed 1 year of endurance training followed by repeat measurements. Pulmonary capillary wedge pressures and LV end-diastolic volumes were measured at baseline, during decreased cardiac filling with lower-body negative pressure, and increased filling with saline infusion. LV compliance was assessed by the slope of the pressure-volume curve. Before training, V̇O2max, LV mass, LV end-diastolic volume, and stroke volume were significantly smaller and the LV was less compliant in sedentary seniors than Masters athletes. One year of exercise training had little effect on cardiac compliance. However, it reduced arterial elastance and improved V̇O2 max by 19% (22.8±3.4 versus 27.2± 4.3 mL/kg/mL; P<0.001). LV mass increased (10%, 64.5±7.9 versus 71.2±12.3 g/m2; P=0.037) with no change in the mass-volume ratio. Conclusions Although 1 year of vigorous exercise training did not appear to favorably reverse cardiac stiffening in sedentary seniors, it nonetheless induced physiological LV remodeling and imparted favorable effects on arterial function and aerobic exercise capacity. PMID:20956204
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Cardiovascular response to prescribed detraining among recreational athletes.
Pedlar, Charles R; Brown, Marcel G; Shave, Robert E; Otto, James M; Drane, Aimee; Michaud-Finch, Jennifer; Contursi, Miranda; Wasfy, Meagan M; Hutter, Adolph; Picard, Michael H; Lewis, Gregory D; Baggish, Aaron L
2018-04-01
Exercise-induced cardiac remodeling (EICR) and the attendant myocardial adaptations characteristic of the athlete's heart may regress during periods of exercise reduction or abstinence. The time course and mechanisms underlying this reverse remodeling, specifically the impact of concomitant plasma volume (PV) contraction on cardiac chamber size, remain incompletely understood. We therefore studied recreational runners ( n = 21, age 34 ± 7 yr; 48% male) who completed an 18-wk training program (~7 h/wk) culminating in the 2016 Boston Marathon after which total exercise exposure was confined to <2 h/wk (no single session >1 h) for 8 wk. Cardiac structure and function, exercise capacity, and PV were assessed at peak fitness (10-14 days before) and at 4 wk and 8 wk postmarathon. Mixed linear modeling adjusting for age, sex, V̇o 2peak , and marathon finish time was used to compare data across time points. Physiological detraining was evidenced by serial reductions in treadmill performance. Two distinct phases of myocardial remodeling and hematological adaptation were observed. After 4 wk of detraining, there were significant reductions in PV (Δ -6.0%, P < 0.01), left ventricular (LV) wall thickness (Δ -8.1%, <0.05), LV mass (Δ -10.3%, P < 0.001), and right atrial area (Δ -8.2%, P < 0.001). After 8 wk of detraining, there was a significant reduction in right ventricle chamber size (end-diastolic area Δ = -8.0%, P < 0.05) without further concomitant reductions in PV or LV wall thickness. Abrupt reductions in exercise training stimulus result in a structure-specific time course of reverse cardiac remodeling that occurs largely independently of PV contraction. NEW & NOTEWORTHY Significant reverse cardiac remodeling, previously documented among competitive athletes, extends to recreational runners and occurs with a distinct time course. Initial reductions in plasma volume and left ventricular (LV) mass, driven by reductions in wall thickness, are followed by contraction of the right ventricle. Consistent with data from competitive athletes, LV chamber volumes appear less responsive to detraining and may be a more permanent adaptation to sport.
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Reddy, G; Nanduri, V B; Basu, A; Modak, M J
1991-08-20
Treatment of murine leukemia virus reverse transcriptase (MuLV RT) with potassium ferrate, an oxidizing agent known to oxidize amino acids involved in phosphate binding domains of proteins, results in the irreversible inactivation of both the DNA polymerase and the RNase H activities. Significant protection from ferrate-mediated inactivation is observed in the presence of template-primer but not in the presence of substrate deoxynucleoside triphosphates. Furthermore, ferrate-treated enzyme loses template-primer binding activity as judged by UV-mediated cross-linking of radiolabeled DNA. Comparative tryptic peptide mapping by reverse-phase HPLC of native and ferrate-oxidized enzyme indicated the presence of two new peptides eluting at 38 and 57 min and a significant loss of a peptide eluting at 74 min. Purification, amino acid composition, and sequencing of these affected peptides revealed that they correspond to amino acid residues 285-295, 630-640, and 586-599, respectively, in the primary amino acid sequence of MuLV RT. These results indicate that the domains constituted by the above peptides are important for the template-primer binding function in MuLV RT. Peptide I is located in the polymerase domain whereas peptides II and III are located in the RNase H domain. Amino acid sequence analysis of peptides I and II suggested Lys-285 and Cys-635 as the probable sites of ferrate action.
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Merchant, Faisal M; Heist, E Kevin; Nandigam, K Veena; Mulligan, Lawrence J; Blendea, Dan; Riedl, Lindsay; McCarty, David; Orencole, Mary; Picard, Michael H; Ruskin, Jeremy N; Singh, Jagmeet P
2010-05-01
Both anatomic interlead separation and left ventricle lead electrical delay (LVLED) have been associated with outcomes following cardiac resynchronization therapy (CRT). However, the relationship between interlead distance and electrical delay in predicting CRT outcomes has not been defined. We studied 61 consecutive patients undergoing CRT for standard clinical indications. All patients underwent intraprocedural measurement of LVLED. Interlead distances in the horizontal (HD), vertical (VD), and direct (DD) dimensions were measured from postprocedure chest radiographs (CXR). Remodeling indices [percent change in left ventricle (LV) ejection fraction, end-diastolic, end-systolic dimensions] were assessed by transthoracic echocardiogram. There was a positive correlation between corrected LVLED and HD on lateral CXR (r = 0.361, P = 0.004) and a negative correlation between LVLED and VD on posteroanterior (PA) CXR (r =-0.281, P = 0.028). To account for this inverse relationship, we developed a composite anatomic distance (defined as: lateral HD-PA VD), which correlated most closely with LVLED (r = 0.404, P = 0.001). Follow-up was available for 48 patients. At a mean of 4.1 +/- 3.2 months, patients with optimal values for both corrected LVLED (>or=75%) and composite anatomic distance (>or=15 cm) demonstrated greater reverse LV remodeling than patients with either one or neither of these optimized values. We identified a significant correlation between LV-right ventricular interlead distance and LVLED; additionally, both parameters act synergistically in predicting LV anatomic reverse remodeling. Efforts to optimize both interlead distance and electrical delay may improve CRT outcomes.
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Iskandrian, A S; Powers, J; Cave, V; Wasserleben, V; Cassell, D; Heo, J
1995-01-01
This study examined the ability of dynamic 123I-labeled iodophenylpentadecanoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease. Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi 123I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34% +/- 11%). The segmental uptake was compared with that of rest-redistribution 201Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11 +/- 5 vs 10 +/- 5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (kappa = 0.78 +/- 0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (kappa = 0.54 +/- 0.04). However, there were more reversible IPPA defects than reversible thallium defects (7 +/- 4 vs 3 +/- 4 segments/patient; p = 0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33% +/- 11% to 39% +/- 12% (p = 0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10 +/- 4 vs 5 +/- 4 segments/patient; p = 0.075). 123I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.
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Tuzun, Egemen; Bick, Roger; Kadipasaoglu, Cihan; Conger, Jeffrey L.; Poindexter, Brian J.; Gregoric, Igor D.; Frazier, O. H.; Towbin, Jeffrey A.; Radovancevic, Branislav
2011-01-01
Purpose. To provide an ovine model of ventricular remodeling and reverse remodeling by creating congestive heart failure (CHF) and then treating it by implanting a left ventricular assist device (LVAD). Methods. We induced volume-overload heart failure in 2 sheep; 20 weeks later, we implanted an LVAD and assessed recovery 11 weeks thereafter. We examined changes in histologic and hemodynamic data and levels of cellular markers of CHF. Results. After CHF induction, we found increases in LV end-diastolic pressure, LV systolic and diastolic dimensions, wall thickness, left atrial diameter, and atrial natriuretic protein (ANP) and endothelin-1 (ET-1) levels; β-adrenergic receptor (BAR) and dystrophin expression decreased markedly. Biopsies confirmed LV remodeling. After LVAD support, LV systolic and diastolic dimensions, wall thickness, and mass, and ANP and ET-1 levels decreased. Histopathologic and hemodynamic markers improved, and BAR and dystrophin expression normalized. Conclusions. We describe a successful sheep model for ventricular and reverse remodeling. PMID:22347659
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Wang, Zhongkai; Chen, Tao; Chen, Liang; Qin, Yongwen; Zhao, Xianxian
2016-01-01
Transcatheter closure is the usual treatment for patent ductus arteriosus (PDA), but its safety and efficacy have not been reported in adult PDA patients with severe mitral regurgitation. A retrospective study on 27 consecutive patients diagnosed with PDA and severe mitral regurgitation and treated using transcatheter closure between September 2010 and September 2012 at the Department of Cardiology of Changhai Hospital in Changhai, China. Left ventricular (LV) diastolic volume and function, pulmonary artery pressure, and instantaneous reverse-flow volume were examined by echocardiography before PDA closure, immediately after closure, and 1 year after closure. After the procedure, the LV diastolic volume (P<.05) and instantaneous reverse-flow volume (P<.001) were significantly decreased. There was no effect on the ejection fraction (P>.05). Pulmonary arterial systolic pressure was unchanged 1 year after closure (from 46.41 ± 19.92 mm Hg to 45.43 ± 13.64 mm Hg; P=.58). All procedures were uneventful and only mild complications occurred (hemolysis in 2 cases, subcutaneous hematoma in 4 cases, and fever in 2 cases). Transcatheter closure can decrease the LV volume and instantaneous reverse-flow volume in adult PDA patients with severe mitral regurgitation. This procedure is effective and has a good safety profile.
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Sun, Cheuk-Kwan; Zhen, Yen-Yi; Leu, Steve; Tsai, Tzu-Hsien; Chang, Li-Teh; Sheu, Jiunn-Jye; Chen, Yung-Lung; Chua, Sarah; Chai, Han-Tan; Lu, Hung-I; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan
2014-05-15
This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation. Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI. LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p<0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31+, CXCR4+, SDF-1α+), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p<0.005). PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Molecular biology of myocardial recovery.
Zhang, Jianyi; Narula, Jagat
2004-02-01
The use of LVADs that leads to a dramatic mechanical and hemodynamic unloading of the failing left ventricle offers a unique opportunity to investigate the mechanisms of remodeling and reverse remodeling. Although it is being increasingly realized that the LVAD unloading results in regression of hypertrophy and improvement of myocyte function and LV geometry, the cellular and molecular mechanisms responsible for these beneficial effects remain undefined. The favorable alterations in geometry that occur in parallel fashion at the organ, cellular, and molecular levels are most likely caused by the reduced LV wall stress/stretch as a consequence of the mechanical support provided by LVAD. If it is confirmed that LVAD unloading can contribute significantly to reverse remodeling, the role of LVADs may graduate from bridge-to-transplantation or destination therapy to bridge-to-recovery.
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Choudhary, Nandlal; Wei, G; Govindarajulu, A; Roy, Avijit; Li, Wenbin; Picton, Deric D; Nakhla, M K; Levy, L; Brlansky, R H
2015-11-01
Citrus leprosis virus C (CiLV-C), a causal agent of the leprosis disease in citrus, is mostly present in the South and Central America and spreading toward the North America. To enable better diagnosis and inhibit the further spread of this re-emerging virus a quantitative (q) real-time reverse transcription polymerase chain reaction (qRT-PCR) assay is needed for early detection of CiLV-C when the virus is present in low titer in citrus leprosis samples. Using the genomic sequence of CiLV-C, specific primers and probe were designed and synthesized to amplify a 73 nt amplicon from the movement protein (MP) gene. A standard curve of the 73 nt amplicon MP gene was developed using known 10(10)-10(1) copies of in vitro synthesized RNA transcript to estimate the copy number of RNA transcript in the citrus leprosis samples. The one-step qRT-PCR detection assays for CiLV-C were determined to be 1000 times more sensitive when compared to the one-step conventional reverse transcription polymerase chain reaction (RT-PCR) CiLV-C detection method. To evaluate the quality of the total RNA extracts, NADH dehydrogenase gene specific primers (nad5) and probe were included in reactions as an internal control. The one-step qRT-PCR specificity was successfully validated by testing for the presence of CiLV-C in the total RNA extracts of the citrus leprosis samples collected from Belize, Costa Rica, Mexico and Panama. Implementation of the one-step qRT-PCR assays for CiLV-C diagnosis should assist regulatory agencies in surveillance activities to monitor the distribution pattern of CiLV-C in countries where it is present and to prevent further dissemination into citrus growing countries where there is no report of CiLV-C presence. Published by Elsevier B.V.
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Zhu, Pengju; Zhang, Yong; Jiang, Peiqing; Wang, Zhongsu; Wang, Jiangrong; Yin, Xiangcui; Hou, Yinglong
2014-08-01
Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). This study was designed to investigate the effects of RFCA on left ventricular (LV) structure and function in AF patients. A systematic literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed to identify trials involving changes of LV structure and function in AF patients undergoing RFCA. Effect size was expressed as weighted mean difference (WMD) with 95% confidence interval (CI). LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were estimated. A total of 21 trials including 1,135 participants were qualified for this meta-analysis. Compared to the baseline values, there were significant decreases in LVEDV (WMD, -6.39 ml; 95%CI, -12.46 to -0.33) and LVESV (WMD, -6.39 ml; 95%CI, -11.35 to -1.42) and a significant improvement in LVEF (WMD, 6.23%; 95%CI, 3.70 to 8.75), but no significant changes were observed in LVEDD (WMD, -0.64 mm; 95%CI, -2.40 to 1.13) and LVESD (WMD, -0.38 mm; 95%CI, -1.32 to 0.56) after RFCA. Subgroup analysis demonstrated that patients with low LVEF (WMD, 11.90%; 95%CI, 9.16 to 14.64) gained more benefits than those with normal LVEF (WMD, 1.56%; 95%CI, 0.38 to 2.74). Besides, patients with chronic AF (WMD, 10.96%; 95%CI, 4.92 to 17.01) improved more than those with paroxysmal AF (WMD, 1.93%; 95%CI, -0.27 to 4.12). RFCA in AF patients could reverse LV structural remodeling and improve LV systolic function, especially in patients with low LVEF and chronic AF.
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Van De Heyning, Caroline M; De Maeyer, Catherine; Pattyn, Nele; Beckers, Paul J; Cornelissen, Véronique A; Goetschalckx, Kaatje; Possemiers, Nadine; Van Craenenbroeck, Emeline M; Voigt, Jens-Uwe; Vanhees, Luc; Shivalkar, Bharati
2018-04-15
Increase of exercise capacity (peak VO 2 ) after cardiac rehabilitation improves outcome in patients with coronary artery disease (CAD). Systolic and diastolic function have been associated with peak VO 2 , but their role towards improvement of exercise capacity remains unclear. It is unknown which exercise intensity has the most beneficial impact on left ventricular (LV) geometry and function in CAD patients without heart failure. 200 stable CAD patients without heart failure were randomized to 3months of aerobic interval training (AIT) or aerobic continuous training (ACT). Cardiopulmonary exercise test and transthoracic echocardiography were scheduled before and after 3months of training. At baseline, a higher peak VO 2 correlated with lower LV posterior wall thickness (p=0.002), higher LV ejection fraction (p=0.008), better LV global longitudinal strain (p=0.043) and lower E/e' (0=0.001). After multivariate stepwise regression analysis only E/é remained an independent predictor of peak VO 2 (p=0.042). Improvement of peak VO 2 after 3months of training correlated with reverse remodeling of the interventricular septum (p=0.005), enlargement of LV diastolic volume (p=0.007) and increase of LV stroke volume (p=0.018) but not with other indices of systolic or diastolic function. Significant reduction of the interventricular septum thickness after cardiac rehabilitation was observed (p=0.012), with a trend towards more reverse remodeling after ACT compared to AIT (p=0.054). In contrast, there were no changes in other parameters of LV geometry, diastolic or systolic function. Systolic and diastolic function are determinants of baseline exercise capacity in CAD patients without heart failure, but do not seem to mediate improvement of peak VO 2 after either AIT or ACT. Copyright © 2017 Elsevier B.V. All rights reserved.
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Changes in Left Ventricular Morphology and Function After Mitral Valve Surgery
Shafii, Alexis E.; Gillinov, A. Marc; Mihaljevic, Tomislav; Stewart, William; Batizy, Lillian H.; Blackstone, Eugene H.
2015-01-01
Degenerative mitral valve disease is the leading cause of mitral regurgitation in North America. Surgical intervention has hinged on symptoms and ventricular changes that develop as compensatory ventricular remodeling takes place. In this study, we sought to characterize the temporal response of left ventricular (LV) morphology and function to mitral valve surgery for degenerative disease, and identify preoperative factors that influence reverse remodeling. From 1986–2007, 2,778 patients with isolated degenerative mitral valve disease underwent valve repair (n=2,607/94%) or replacement (n=171/6%) and had at least 1 postoperative transthoracic echocardiogram (TTE); 5,336 TTEs were available for analysis. Multivariable longitudinal repeated-measures analysis was performed to identify factors associated with reverse remodeling. LV dimensions decreased in the first year after surgery (end-diastolic from 5.7±0.80 to 4.9±1.4 cm; end-systolic from 3.4±0.71 to 3.1±1.4 cm). LV mass index decreased from 139±44 to 112±73 g·m−2. Reduction of LV hypertrophy was less pronounced in patients with greater preoperative left heart enlargement (P<.0001) and greater preoperative LV mass (P<.0001). Postoperative LV ejection fraction initially decreased from 58±7.0 to 53±20, increased slightly over the first postoperative year, and was negatively influenced by preoperative heart failure symptoms (P<.0001) and lower preoperative LV ejection fraction (P<.0001). Risk-adjusted response of LV morphology and function to valve repair and replacement was similar (P>.2). In conclusion, a positive response toward normalization of LV morphology and function after mitral valve surgery is greatest in the first year. The best response occurs when surgery is performed before left heart dilatation, LV hypertrophy, or LV dysfunction develop. PMID:22534055
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Kidney, B A; Ellis, J A; Haines, D M; Jackson, M L
2001-12-01
To determine whether feline vaccine site-associated sarcomas (VSS) contain a higher amount of endogenous FeLV (enFeLV) RNA, compared with feline nonvaccine site-associated sarcomas (non-VSS). Formalin-fixed paraffin-embedded (FFPE) tissues from 50 VSS and 50 cutaneous non-VSS. RNA was extracted from FFPE sections of each tumor, and regions of the long terminal repeat (LTR) and envelope (env) gene of enFeLV were amplified by use of reverse transcriptase-polymerase chain reaction (RT-PCR). The density of each RT-PCR product band for enFeLV was compared with that of a constitutively expressed gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). An integrated density value (IDV) was determined by use of densitometry, and the IDV ratio for enFeLV to GAPDH was calculated for each enFeLV primer set. The median (interquartile range) of the IDV ratio for the enFeLV LTR primer set was 0.52 (0.26 to 1.17) for the VSS group and 0.84 (0.21 to 1.53) for the non-VSS group. The median (interquartile range) of the IDV ratio for the enFeLV env primer set was 0.60 (0.37 to 0.91) for the VSS group and 0.59 (0.36 to 1.09) for the non-VSS group. Because the amount of enFeLV RNA within the LTR and env gene was not significantly different between the VSS and non-VSS groups, enFeLV replication or expression is unlikely to be involved in VSS development.
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D'Andrea, Antonello; De Rimini, Maria Luisa; America, Raffaella; Cirillo, Chiara; Riegler, Lucia; Limongelli, Giuseppe; D'Alto, Michele; Salerno, Gemma; Maiello, Ciro; Muto, Pietro; Russo, Maria Giovanna; Calabrò, Raffaele; Bossone, Eduardo; Pacileo, Giuseppe
2017-10-01
The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up. © 2017, Wiley Periodicals, Inc.
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Gammaretrovirus-Specific Antibodies in Free-Ranging and Captive Namibian Cheetahs
Krengel, Annika; Cattori, Valentino; Meli, Marina L.; Wachter, Bettina; Böni, Jürg; Bisset, Leslie R.; Thalwitzer, Susanne; Melzheimer, Jörg; Jago, Mark; Hofmann-Lehmann, Regina; Hofer, Heribert
2015-01-01
The cheetah population in Namibia is the largest free-ranging population in the world and a key population for research regarding the health status of this species. We used serological methods and quantitative real-time PCR to test free-ranging and captive Namibian cheetahs for the presence of feline leukemia virus (FeLV), a gammaretrovirus that can be highly aggressive in populations with low genetic diversity, such as cheetahs. We also assessed the presence of antibodies to other gammaretroviruses and the responses to a FeLV vaccine developed for domestic cats. Up to 19% of the free-ranging cheetahs, 27% of the captive nonvaccinated cheetahs, and 86% of the captive vaccinated cheetahs tested positive for FeLV antibodies. FeLV-antibody-positive free-ranging cheetahs also tested positive for Rauscher murine leukemia virus antibodies. Nevertheless, FeLV was not detectable by quantitative real-time PCR and no reverse transcriptase activity was detectable by product-enhanced reverse transcriptase assay in the plasma of cheetahs or the supernatants from cultures of peripheral blood mononuclear cells. The presence of antibodies to gammaretroviruses in clinically healthy specimens may be caused either by infection with a low-pathogenic retrovirus or by the expression of endogenous retroviral sequences. The strong humoral immune responses to FeLV vaccination demonstrate that cheetahs can respond to the vaccine and that vaccination against FeLV infection may be beneficial should FeLV infection ever become a threat, as was seen in Iberian lynx and Florida panthers. PMID:25809630
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Cheng, Yanping; Aboodi, Michael S.; Wechsler, Andrew S.; Kaluza, Greg L.; Granada, Juan F.; Van Bladel, Kevin; Annest, Lon S.; Yi, Geng-Hua
2013-01-01
OBJECTIVES Surgical ventricular reconstruction has been used to treat ischaemic cardiomyopathy with large akinetic or dyskinetic areas. However, application of this approach requires a sternotomy, cardiopulmonary bypass and a left ventriculotomy. This study assessed the feasibility and efficacy of minimally invasive, off-pump, epicardial catheter-based ventricular reconstruction (ECVR) in an anteroapical aneurysm ovine model. METHODS Left ventricular (LV) anteroapical myocardial infarction was induced percutaneously by coil embolization of the left anterior descending coronary artery. Eight weeks after infarction, via mini left thoracotomy and without cardiopulmonary bypass, ECVR was performed in six sheep. The scar was excluded by placing anchor pairs on the LV epicardial anterior wall and the right ventricular side of the interventricular septum under fluoroscopic guidance. LV performance was evaluated before, immediately after device implantation and after 6 weeks by echocardiography. Terminal histopathology was performed. RESULTS ECVR was completed expeditiously in all animals without complications. Parameters obtained 6 weeks after device implantation were compared with baseline (pre-device). End-systolic volume was decreased by 38% (25.6 ± 6.1 ml vs baseline 41.2 ± 7.2 ml, P = 0.02) with preservation of stroke volume. Ejection fraction was significantly increased by 13% (48.5 ± 7% vs baseline 35.8 ± 7%, P = 0.02). The circumferential strain in the anterior septum (−7.67 ± 5.12% vs baseline −0.96 ± 2.22%, P = 0.03) and anterior wall (−9.01 ± 3.51% vs baseline −4.15 ± 1.36%, P = 0.01) were significantly improved. The longitudinal strain in apex was reversed (−3.08 ± 1.53% vs baseline 3.09 ± 3.39%, P = 0.01). Histopathology showed full endocardial healing over the anchors with appreciable reduction of the chronic infarct in the LV. CONCLUSIONS ECVR without cardiopulmonary bypass is a less invasive alternative to current standard therapies, reverses LV remodelling and improves cardiac performance in an ovine model of anteroapical aneurysm. PMID:23985410
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Kusunose, Kenya; Zhang, Youhua; Mazgalev, Todor N; Thomas, James D; Popović, Zoran B
2013-12-05
Recently, left ventricular (LV) strain distribution pattern has been assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in terms of global LV dysfunction but with poor understanding of regional variability in LV function. We hypothesized that TIC induces specific changes in LV strain distribution pattern. Twenty five adult mongrel conscious dogs were trained to lie down calmly for echocardiography. In seven selected dogs, we implanted pacing system for TIC induction under general anesthesia. We measured LV geometry and function, strains, and torsion before and after the development of TIC in awake non-sedated state. In 25 healthy dogs, all three types of normal strain significantly increased from base to apex (p <0.05), while a definite and recognizable twist could be measured due to presence of shear strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05), and negative peak twist rate (p <0.05). Interestingly, the relative decrease of strain due to TIC was more pronounced in the apex (p < 0.001), with the radial strain decreasing the most (p < 0.05). TIC is accompanied by decreased systolic LV strain and twist deformation, as well as loss of early diastolic recoil. In addition, the decrease of strain was more profound in the apex. This "reverse" distribution of LV strain may help us understand LV dysfunction in the presence of nonischemic etiology.
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Bodi, Vicente; Monmeneu, Jose V; Ortiz-Perez, Jose T; Lopez-Lereu, Maria P; Bonanad, Clara; Husser, Oliver; Minana, Gemma; Gomez, Cristina; Nunez, Julio; Forteza, Maria J; Hervas, Arantxa; de Dios, Elena; Moratal, David; Bosch, Xavier; Chorro, Francisco J
2016-01-01
To assess predictors of reverse remodeling by using cardiac magnetic resonance (MR) imaging soon after ST-segment-elevation myocardial infarction (STEMI). Written informed consent was obtained from all patients, and the study protocol was approved by the institutional committee on human research, ensuring that it conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Five hundred seven patients (mean age, 58 years; age range, 24-89 years) with a first STEMI were prospectively studied. Infarct size and microvascular obstruction (MVO) were quantified at late gadolinium-enhanced imaging. Reverse remodeling was defined as a decrease in left ventricular (LV) end-systolic volume index (LVESVI) of more than 10% from 1 week to 6 months after STEMI. For statistical analysis, a simple (from a clinical perspective) multiple regression model preanalyzing infarct size and MVO were applied via univariate receiver operating characteristic techniques. Patients with reverse remodeling (n = 211, 42%) had a lesser extent (percentage of LV mass) of 1-week infarct size (mean ± standard deviation: 18% ± 13 vs 23% ± 14) and MVO (median, 0% vs 0%; interquartile range, 0%-1% vs 0%-4%) than those without reverse remodeling (n = 296, 58%) (P < .001 in pairwise comparisons). The independent predictors of reverse remodeling were infarct size (odds ratio, 0.98; 95% confidence interval [CI]: 0.97, 0.99; P = .04) and MVO (odds ratio, 0.92; 95% CI: 0.86, 0.99; P = .03). Once infarct size and MVO were dichotomized by using univariate receiver operating characteristic techniques, the only independent predictor of reverse remodeling was the presence of simultaneous nonextensive infarct-size MVO (infarct size < 30% of LV mass and MVO < 2.5% of LV mass) (odds ratio, 3.2; 95% CI: 1.8, 5.7; P < .001). Assessment of infarct size and MVO with cardiac MR imaging soon after STEMI enables one to make a decision in the prediction of reverse remodeling. © RSNA, 2015
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Ozcan, Cevher; Jahangir, Arshad; Friedman, Paul A; Munger, Thomas M; Packer, Douglas L; Hodge, David O; Hayes, David L; Gersh, Bernard J; Hammill, Stephen C; Shen, Win-Kuang
2003-07-01
Control of ventricular rate by atrioventricular node ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation (AF) is associated with improved left ventricular (LV) function. The objective of this study was to determine the effect of atrioventricular node ablation on long-term survival in patients with AF and LV dysfunction. Survival was determined by the Kaplan-Meier method for 56 study patients with LV ejection fraction (EF) < or =40% who underwent atrioventricular node ablation and pacemaker implantation and 56 age- and gender-matched control patients with AF and LVEF >40%, and age- and gender-matched control subjects from Minnesota. Groups were compared using the log-rank test. In study patients (age 69 +/- 10 years; 45 men), LVEF was 26% +/- 8% and 34% +/- 13% (p <0.001) before and after ablation, respectively. During follow-up (40 +/- 23 months), 23 patients died. Observed survival was worse than that of normal subjects (p <0.001) and control patients (p = 0.005). After ablation, LVEF nearly normalized (> or =45%) in 16 study patients (29%), in whom observed survival was comparable to that of normal subjects (p = 0.37). Coronary artery disease, hyperlipidemia, chronic renal failure, previous myocardial infarction, and coronary artery operation were independent predictors for mortality. Near normalization of LVEF occurred in 29% of study patients, suggesting that AF-induced EF reduction is reversible in many patients. Normal survival in patients with reversible LV dysfunction highlights potential survival benefits of rate control. Poor survival in patients with persistent LV dysfunction confirms the importance of optimal medical therapy.
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Gupta, Saurabh Kumar; Krishnamoorthy, Km; Tharakan, Jaganmohan A; Sivasankaran, S; Sanjay, G; Bijulal, S; Anees, T
2011-07-01
To evaluate the effect of percutaneous closure of patent ductus arteriosus (PDA) on left ventricular (LV) systolic and diastolic function in children. Limited studies are available on alteration in LV hemodynamics, especially diastolic function, after PDA closure. Thirty-two consecutive children with isolated PDA treated by trans-catheter closure were studied. The LV systolic and diastolic function were assessed by two-dimensional (2D) echocardiography and tissue Doppler imaging 1 day before the PDA closure, on day 1, and on follow-up. At baseline, none of the patients had LV systolic dysfunction. On day 1 post-PDA closure, 8 (25%) children developed LV systolic dysfunction. The baseline LV ejection fraction (LVEF), LV end-systolic dimension (LVESD), and PDA diastolic gradient predicted the post-closure LVEF. Patients who developed post-closure LV systolic dysfunction had poorer LV diastolic function than those who did not. LV diastolic properties improved after PDA closure; however, the improvement in LV diastolic properties lagged behind the improvement in the LV systolic function. All children were asymptomatic and had normal LVEF on follow up of >3 months. Percutaneous closure of PDA is associated with the reversible LV systolic dysfunction. Improvement in the LV diastolic function lags behind that in the LV systolic function.
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Gammaretrovirus-specific antibodies in free-ranging and captive Namibian cheetahs.
Krengel, Annika; Cattori, Valentino; Meli, Marina L; Wachter, Bettina; Böni, Jürg; Bisset, Leslie R; Thalwitzer, Susanne; Melzheimer, Jörg; Jago, Mark; Hofmann-Lehmann, Regina; Hofer, Heribert; Lutz, Hans
2015-06-01
The cheetah population in Namibia is the largest free-ranging population in the world and a key population for research regarding the health status of this species. We used serological methods and quantitative real-time PCR to test free-ranging and captive Namibian cheetahs for the presence of feline leukemia virus (FeLV), a gammaretrovirus that can be highly aggressive in populations with low genetic diversity, such as cheetahs. We also assessed the presence of antibodies to other gammaretroviruses and the responses to a FeLV vaccine developed for domestic cats. Up to 19% of the free-ranging cheetahs, 27% of the captive nonvaccinated cheetahs, and 86% of the captive vaccinated cheetahs tested positive for FeLV antibodies. FeLV-antibody-positive free-ranging cheetahs also tested positive for Rauscher murine leukemia virus antibodies. Nevertheless, FeLV was not detectable by quantitative real-time PCR and no reverse transcriptase activity was detectable by product-enhanced reverse transcriptase assay in the plasma of cheetahs or the supernatants from cultures of peripheral blood mononuclear cells. The presence of antibodies to gammaretroviruses in clinically healthy specimens may be caused either by infection with a low-pathogenic retrovirus or by the expression of endogenous retroviral sequences. The strong humoral immune responses to FeLV vaccination demonstrate that cheetahs can respond to the vaccine and that vaccination against FeLV infection may be beneficial should FeLV infection ever become a threat, as was seen in Iberian lynx and Florida panthers. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.
Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe
2014-11-01
Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.
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Ji, Pei-Feng; Yao, Cui-Luan; Wang, Zhi-Yong
2011-08-01
Calmodulin (CaM) plays an important role in calcium-dependent signal transduction pathways. In the present study, two alternative splicing isoforms of CaM (named LvCaM-A and LvCaM-B) cDNA were cloned from the Pacific white shrimp, Litopenaeus vannamei. LvCaM-A was of 1101 bp, including a 5'-terminal untranslated region (UTR) of 70 bp, a 3'-terminal UTR of 581 bp and an open reading frame (ORF) of 450 bp encoding a polypeptide of 149 amino acids with a calculated molecular weight (Mw) of 17 kDa and pI of 4.41. LvCaM-B was 689 bp, including a same 5'-UTR of 70 bp, a 3'-terminal UTR of 109 bp and an ORF of 510 bp encoding a polypeptide of 169 amino acids with a calculated Mw of 19 kDa and pI of 4.36. Both LvCaM-A and LvCaM-B contained 4 conservative EF-hand motifs. Quantitative real-time reverse transcription PCR analysis revealed LvCaM-A to be expressed in most shrimp tissues, with the predominant expression in nerve and the weakest expression in heart. However, LvCaM-B expression level was much weaker than those of LvCaM-A in all the tested tissues with main expression in hepatopancreas. The expression of LvCaM-A and LvCaM-B after challenge with Vibrio parahaemolyticus and WSSV were tested in hemocytes, hepatopancreas and nerve. The results indicated that LvCaM-A and LvCaM-B transcripts could be significantly induced in hemocytes and hepatopancreas respectively by injection with V. parahaemolyticus. The highest expression of LvCaM-A was in the hemocytes with 2.3 times (at 48 h) greater expression than in the control (p < 0.05). However, sharp down-regulation of both LvCaM-A and LvCaM-B were detected in nerve after Vibrio- and WSSV injection (p < 0.05). These results suggested that CaM might play an important role in shrimp's defense against pathogenic infection. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Ho, Chia-Fang; Chan, Kun-Wei; Yang, Wei-Cheng; Chiang, Yu-Chung; Chung, Yang-Tsung; Kuo, James; Wang, Chi-Young
2014-07-01
A multiplex amplification refractory mutation system reverse transcription polymerase chain reaction (ARMS RT-PCR) was developed for the differential diagnosis of Feline leukemia virus (FeLV) vaccine and wild-type strains based on a point mutation between the vaccine strain (S) and the wild-type strain (T) located in the p27 gene. This system was further upgraded to obtain a real-time ARMS RT-PCR (ARMS qRT-PCR) with a high-resolution melt analysis (HRMA) platform. The genotyping of various strains of FeLV was determined by comparing the HRMA curves with the defined wild-type FeLV (strain TW1), and the results were expressed as a percentage confidence. The detection limits of ARMS RT-PCR and ARMS qRT-PCR combined with HRMA were 100 and 1 copies of transcribed FeLV RNA per 0.5 ml of sample, respectively. No false-positive results were obtained with 6 unrelated pathogens and 1 feline cell line. Twelve FeLV Taiwan strains were correctly identified using ARMS qRT-PCR combined with HRMA. The genotypes of the strains matched the defined FeLV wild-type strain genotype with at least 91.17% confidence. A higher degree of sequence polymorphism was found throughout the p27 gene compared with the long terminal repeat region. In conclusion, the current study describes the phylogenetic relationship of the FeLV Taiwan strains and demonstrates that the developed ARMS RT-PCR assay is able to be used to detect the replication of a vaccine strain that has not been properly inactivated, thus acting as a safety check for the quality of FeLV vaccines.
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Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study
Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe
2014-01-01
Background: Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. Objectives: The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Methods: Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism. Results: Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Conclusion: Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism. PMID:25093618
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Dery, Kenneth J; Silver, Craig; Yang, Lu; Shively, John E
2018-06-15
The adhesion protein carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is widely expressed in epithelial cells as a short cytoplasmic isoform (S-iso) and in leukocytes as a long cytoplasmic isoform (L-iso) and is frequently silenced in cancer by unknown mechanisms. Previously, we reported that interferon response factor 1 (IRF1) biases alternative splicing (AS) to include the variable exon 7 (E7) in CEACAM1, generating long cytoplasmic isoforms. We now show that IRF1 and a variant of heterogeneous nuclear ribonucleoprotein L (Lv1) coordinately silence the CEACAM1 gene. RNAi-mediated Lv1 depletion in IRF1-treated HeLa and melanoma cells induced significant CEACAM1 protein expression, reversed by ectopic Lv1 expression. The Lv1-mediated CEACAM1 repression resided in residues Gly 71 -Gly 89 and Ala 38 -Gly 89 in Lv1's N-terminal extension. ChIP analysis of IRF1- and FLAG-tagged Lv1-treated HeLa cells and global treatment with the global epigenetic modifiers 5-aza-2'-deoxycytidine and trichostatin A indicated that IRF1 and Lv1 together induce chromatin remodeling, restricting IRF1 access to the CEACAM1 promoter. In interferon γ-treated HeLa cells, the transcription factor SP1 did not associate with the CEACAM1 promoter, but binding by upstream transcription factor 1 (USF1), a known CEACAM1 regulator, was greatly enhanced. ChIP-sequencing revealed that Lv1 overexpression in IRF1-treated cells induces transcriptional silencing across many genes, including DCC ( d eleted in c olorectal c arcinoma), associated with CEACAM5 in colon cancer. Notably, IRF1, but not IRF3 and IRF7, affected CEACAM1 expression via translational repression. We conclude that IRF1 and Lv1 coordinately regulate CEACAM1 transcription, alternative splicing, and translation and may significantly contribute to CEACAM1 silencing in cancer. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
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Adjuvant FOLFOX chemotherapy and splenomegaly in patients with stages II-III colorectal cancer.
Angitapalli, Revathi; Litwin, Alan M; Kumar, Prasanna R G; Nasser, Eiad; Lombardo, Jeffrey; Mashtare, Terry; Wilding, Gregory E; Fakih, Marwan G
2009-01-01
The impact of adjuvant chemotherapy on hepatic function and portal hypertension in patients with stages II-III colon cancer has not been previously described. We conducted a retrospective study to assess the effects of adjuvant FOLFOX chemotherapy on the splenic index (SI) as a surrogate marker for portal hypertension. Stage II-III colorectal cancer patients treated with adjuvant FOLFOX or fluorouracil/leucovorin (5-FU/LV) at Roswell Park Cancer Institute between 2002 and 2006 were identified. Computerizedt omography (CT) scans obtained prior to and at completion of chemotherapy, and every 6 months thereafter were reviewed. Splenic size was evaluated using the SI (SI = length x width x height of the spleen). 40 patients were identified in the FOLFOX group and 23 in the 5-FU/LV group. After 6 months of adjuvant chemotherapy, the mean increase in SI was 45.7 and 16.3% in the FOLFOX and 5-FU/LV groups, respectively (p = 0.0069). SI increased by >100% in 6 patients (15%) in the FOLFOX group versus none in the 5-FU/LV group (p = 0.16). The mean SI at completion of adjuvant chemotherapy was significantly higher in the FOLFOX group than in the 5-FU/LV group (p = 0.007). The mean SI decreased steadily over a period of 2 years after discontinuation of FOLFOX, suggesting potential reversibility of oxaliplatin-induced hepatic injury in this setting. Adjuvant FOLFOX significantly increases the SI in patients with resected colorectal cancer in comparison to adjuvant 5-FU/LV. The increase in SI may be a marker of oxaliplatin-induced hepatic injury and should be investigated further in prospective longitudinal studies of oxaliplatin-based adjuvant chemotherapy. Copyright 2009 S. Karger AG, Basel.
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O'Connell, Michael J.; Lavery, Ian; Yothers, Greg; Paik, Soonmyung; Clark-Langone, Kim M.; Lopatin, Margarita; Watson, Drew; Baehner, Frederick L.; Shak, Steven; Baker, Joffre; Cowens, J. Wayne; Wolmark, Norman
2010-01-01
Purpose These studies were conducted to determine the relationship between quantitative tumor gene expression and risk of cancer recurrence in patients with stage II or III colon cancer treated with surgery alone or surgery plus fluorouracil (FU) and leucovorin (LV) to develop multigene algorithms to quantify the risk of recurrence as well as the likelihood of differential treatment benefit of FU/LV adjuvant chemotherapy for individual patients. Patients and Methods We performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) on RNA extracted from fixed, paraffin-embedded (FPE) tumor blocks from patients with stage II or III colon cancer who were treated with surgery alone (n = 270 from National Surgical Adjuvant Breast and Bowel Project [NSABP] C-01/C-02 and n = 765 from Cleveland Clinic [CC]) or surgery plus FU/LV (n = 308 from NSABP C-04 and n = 508 from NSABP C-06). Overall, 761 candidate genes were studied in C-01/C-02 and C-04, and a subset of 375 genes was studied in CC/C-06. Results A combined analysis of the four studies identified 48 genes significantly associated with risk of recurrence and 66 genes significantly associated with FU/LV benefit (with four genes in common). Seven recurrence-risk genes, six FU/LV-benefit genes, and five reference genes were selected, and algorithms were developed to identify groups of patients with low, intermediate, and high likelihood of recurrence and benefit from FU/LV. Conclusion RT-qPCR of FPE colon cancer tissue applied to four large independent populations has been used to develop multigene algorithms for estimating recurrence risk and benefit from FU/LV. These algorithms are being independently validated, and their clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR) study. PMID:20679606
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O'Connell, Michael J; Lavery, Ian; Yothers, Greg; Paik, Soonmyung; Clark-Langone, Kim M; Lopatin, Margarita; Watson, Drew; Baehner, Frederick L; Shak, Steven; Baker, Joffre; Cowens, J Wayne; Wolmark, Norman
2010-09-01
These studies were conducted to determine the relationship between quantitative tumor gene expression and risk of cancer recurrence in patients with stage II or III colon cancer treated with surgery alone or surgery plus fluorouracil (FU) and leucovorin (LV) to develop multigene algorithms to quantify the risk of recurrence as well as the likelihood of differential treatment benefit of FU/LV adjuvant chemotherapy for individual patients. We performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) on RNA extracted from fixed, paraffin-embedded (FPE) tumor blocks from patients with stage II or III colon cancer who were treated with surgery alone (n = 270 from National Surgical Adjuvant Breast and Bowel Project [NSABP] C-01/C-02 and n = 765 from Cleveland Clinic [CC]) or surgery plus FU/LV (n = 308 from NSABP C-04 and n = 508 from NSABP C-06). Overall, 761 candidate genes were studied in C-01/C-02 and C-04, and a subset of 375 genes was studied in CC/C-06. A combined analysis of the four studies identified 48 genes significantly associated with risk of recurrence and 66 genes significantly associated with FU/LV benefit (with four genes in common). Seven recurrence-risk genes, six FU/LV-benefit genes, and five reference genes were selected, and algorithms were developed to identify groups of patients with low, intermediate, and high likelihood of recurrence and benefit from FU/LV. RT-qPCR of FPE colon cancer tissue applied to four large independent populations has been used to develop multigene algorithms for estimating recurrence risk and benefit from FU/LV. These algorithms are being independently validated, and their clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR) study.
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Effect of Ranolazine on Left Ventricular Dyssynchrony in Patients with Coronary Artery Disease
Venkataraman, Rajesh; Chen, Ji; Garcia, Ernest V.; Belardinelli, Luiz; Hage, Fadi G.; Heo, Jaekyeong; Iskandrian, Ami E.
2012-01-01
We previously reported that ranolazine improved exercise myocardial perfusion. Ranolazine ameliorates myocardial ischemia by augmenting myocardial blood flow; likely due to a reduction in extra-vascular compression of small vessels. We hypothesized that ranolazine could improve left ventricular (LV) dyssynchrony as assessed by phase analysis of gated SPECT myocardial perfusion imaging (MPI). Patients (n=32) with known or suspected coronary artery disease and reversible perfusion defects on a clinically indicated stress MPI were re-studied 4 weeks after ranolazine (500–1000 mg orally twice daily) was added to their conventional treatment in an open-label trial (data previously reported). The LV systolic and diastolic dyssynchrony indices were obtained using automated phase analysis before and after ranolazine. There were no significant changes in heart rate and blood pressure (at rest or during stress) after treatment. The perfusion pattern improved in 13 of 18 patients who had exercise testing but in only 3 of 14 patients who had vasodilator stress testing. There were no significant changes in LV ejection fraction or volumes after treatment. The systolic and diastolic LV dyssynchrony improved after ranolazine therapy; there was a significant decrease in systolic phase standard deviation (SD) (21±17 vs. 18±13, P=0.04), systolic bandwidth (BW) (69±60 vs. 53±38, P=0.03), diastolic SD (29±18 vs. 24±15, P=0.047) and diastolic BW (91±61 vs. 72±45, P=0.02). In conclusion, this is the first study to show improvement in diastolic and systolic LV synchrony with ranolazine as measured by automated phase analysis of gated SPECT MPI. PMID:22884560
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Ghanta, Ravi K; Rangaraj, Aravind; Umakanthan, Ramanan; Lee, Lawrence; Laurence, Rita G; Fox, John A; Bolman, R Morton; Cohn, Lawrence H; Chen, Frederick Y
2007-03-13
Ventricular restraint is a nontransplantation surgical treatment for heart failure. The effect of varying restraint level on left ventricular (LV) mechanics and remodeling is not known. We hypothesized that restraint level may affect therapy efficacy. We studied the immediate effect of varying restraint levels in an ovine heart failure model. We then studied the long-term effect of restraint applied over a 2-month period. Restraint level was quantified by use of fluid-filled epicardial balloons placed around the ventricles and measurement of balloon luminal pressure at end diastole. At 4 different restraint levels (0, 3, 5, and 8 mm Hg), transmural myocardial pressure (P(tm)) and indices of myocardial oxygen consumption (MVO2) were determined in control (n=5) and ovine heart failure (n=5). Ventricular restraint therapy decreased P(tm) and MVO2, and improved mechanical efficiency. An optimal physiological restraint level of 3 mm Hg was identified to maximize improvement without an adverse affect on systemic hemodynamics. At this optimal level, end-diastolic P(tm) and MVO2 indices decreased by 27% and 20%, respectively. The serial longitudinal effects of optimized ventricular restraint were then evaluated in ovine heart failure with (n=3) and without (n=3) restraint over 2 months. Optimized ventricular restraint prevented and reversed pathological LV dilatation (130+/-22 mL to 91+/-18 mL) and improved LV ejection fraction (27+/-3% to 43+/-5%). Measured restraint level decreased over time as the LV became smaller, and reverse remodeling slowed. Ventricular restraint level affects the degree of decrease in P(tm), the degree of decrease in MVO2, and the rate of LV reverse remodeling. Periodic physiological adjustments of restraint level may be required for optimal restraint therapy efficacy.
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Prenatal diagnosis of prevalence of the right heart: associated anomalies and outcome predictors.
Peng, Ruan; Xie, Hong-Ning; Zhu, Yun-Xiao; Li, Li-Juan; Du, Liu; Zheng, Ju
2014-07-01
To analyze the characteristics, associations, and outcomes of prevalence of the right heart and to evaluate the use of sonography to predict the risk of a poor prognosis in fetuses with this condition. We conducted a retrospective cohort study of 182 fetuses with prevalence of the right heart. At the initial evaluation, the left ventricle (LV) and right ventricle (RV) sizes, left atrium and right atrium sizes, great artery diameters, appearance of the aortic arch and ductus arteriosus arch, and flow direction across the foramen ovale and aortic arch were documented. Malformations were documented in fetuses with intracardiac anomalies, who were divided into groups with and without coexisting extracardiac defects. The RV-LV diameter ratio and main pulmonary artery-to-aortic root diameter ratio were calculated and compared. The following variables were analyzed: coexisting intracardiac anomalies, associated extracardiac anomalies, diagnosis before 24 gestational weeks, fetal growth restriction, reversed flow across the foramen ovale, reversed flow in the aortic arch, and RV-LV ratio greater than 2.0. Relationships between these sonographic findings and the prognosis were evaluated by multivariable logistic regression. Of the 182 fetuses, 1 (0.5%) had intrauterine death, and 25 (13.7%) had neonatal death; 1 (0.5%) had selective reduction, and 106 (58.2%) underwent termination of pregnancy; 49 (26.9%) survived at this writing. The mean RV-LV ratio was 1.67. Multivariable logistic regression revealed that only 2 sonographic parameters, coexisting intracardiac anomalies (odds ratio, 17.75; 95% confidence interval, 4.18-75.26) and diagnosis before 24 weeks (odds ratio, 17.26; 95% confidence interval, 1.80-165.39) were significantly associated with a poor prognosis. The sonographic parameters of coexisting intracardiac anomalies and diagnosis before 24 gestational weeks are significant independent predictors of a poor prognosis in fetuses with prevalence of the right heart. Combinations of these risk factors may be useful in prenatal consultation. © 2014 by the American Institute of Ultrasound in Medicine.
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Broadening the use of antiretroviral therapy: the case for feline leukemia virus
Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M
2011-01-01
Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action. PMID:21479142
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Fujimoto, Naoki; Hastings, Jeffrey L.; Carrick-Ranson, Graeme; Shafer, Keri M.; Shibata, Shigeki; Bhella, Paul S.; Abdullah, Shuaib M.; Barkley, Kyler W.; Adams-Huet, Beverley; Boyd, Kara N.; Livingston, Sheryl A.; Palmer, Dean; Levine, Benjamin D.
2014-01-01
Background Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise combined with alagebrium would improve LV stiffness in sedentary older humans. Methods and Results Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define LV pressure–volume curves; secondary functional outcomes included cardiopulmonary exercise testing and arterial compliance. A total of 57 of 62 subjects (67±6 years; 37 f/20 m) completed 1 year of intervention followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the slope of LV pressure–volume curve. After intervention, LV mass and end-diastolic volume increased and exercise capacity improved (by ≈8%) only in the exercise groups. Neither LV mass nor exercise capacity was affected by alagebrium. Exercise training had little impact on LV stiffness (training×time effect, P=0.46), whereas alagebrium showed a modest improvement in LV stiffness compared with placebo (medication×time effect, P=0.04). Conclusions Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening. PMID:24130005
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Butler, Craig R; Jugdutt, Bodh I
2012-09-01
Dilated cardiomyopathy (DCM) is a common debilitating condition with limited therapeutic options besides heart transplantation or palliation. It is characterized by maladaptive remodeling of cardiomyocytes, extracellular collagen matrix (ECCM) and left ventricular (LV) geometry which contributes to further dysfunction. LV assist devices (LVADs) can reverse adverse remodeling in end-stage DCM. However, there is a disconnect between the benefits of prolonged unloading with LVAD at molecular and cellular levels and the low rate of bridge to recovery (BTR). Potential explanations for this paradox include insufficient reverse ECCM remodeling and/or excessive reverse cardiomyocyte remodeling with atrophy. LVAD therapy is associated with decreased collagen turnover and cross-linking and increased tissue angiotensin II (AngII), whereas LVAD combined with angiotensin-converting enzyme inhibition results in decreased tissue AngII and collagen cross-linking, normalizes LV end-diastolic pressure volume relationships and is associated with modestly higher rates of BTR. Much remains to be learned about ventricular reverse remodeling after LVAD. This can be facilitated through systematic collection and comparison of recovered and unrecovered myocardium. Importantly, vigilant monitoring for ventricular recovery among LVAD patients is needed, particularly in older patients receiving LVAD for destination therapy. In addition, prospective multicenter trials are needed to clarify the potential benefit of concomitant heart failure therapy with selective β2 agonism on ventricular recovery.
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Simulated Microgravity and Recovery-Induced Remodeling of the Left and Right Ventricle
Zhong, Guohui; Li, Yuheng; Li, Hongxing; Sun, Weijia; Cao, Dengchao; Li, Jianwei; Zhao, Dingsheng; Song, Jinping; Jin, Xiaoyan; Song, Hailin; Yuan, Xinxin; Wu, Xiaorui; Li, Qi; Xu, Qing; Kan, Guanghan; Cao, Hongqing; Ling, Shukuan; Li, Yingxian
2016-01-01
Physiological adaptations to microgravity involve alterations in cardiovascular systems. These adaptations result in cardiac remodeling and orthostatic hypotension. However, the response of the left ventricle (LV) and right ventricle (RV) following hindlimb unloading (HU) and hindlimb reloading (HR) is not clear and the underlying mechanism remains to be understood. In this study, three groups of mice were subjected to HU by tail suspension for 28 days. Following this, two groups were allowed to recover for 7 or 14 days. The control group was treated equally, with the exception of tail suspension. Echocardiography was performed to detect the structure and function changes of heart. Compared with the control, the HU group of mice showed reduced LV-EF (ejection fraction), and LV-FS (fractional shortening). However, mice that were allowed to recover for 7 days after HU (HR-7d) showed increased LVIDs (systolic LV internal diameter) and LV Vols (systolic LV volume). Mice that recovered for 14 days (HR-14d) returned to the normal state. In comparison, RV-EF and RV-FS didn't recover to the normal conditions till being reloaded for 14 days. Compared with the control, RVIDd (diastolic RV internal diameter), and RV Vold (diastolic RV volume) were reduced in HU group and recovered to the normal conditions in HR-7d and HR-14d groups, in which groups RVIDs (systolic RV internal diameter) and RV Vols (systolic RV volume) were increased. Histological analysis and cardiac remodeling gene expression results indicated that HU induces left and right ventricular remodeling. Western blot demonstrated that the phosphorylation of HDAC4 and ERK1/2 and the ratio of LC3-II / LC3-I, were increased following HU and recovered following HR in both LV and RV, and the phosphorylation of AMPK was inhibited in both LV and RV following HU, but only restored in LV following HR for 14 days. These results indicate that simulated microgravity leads to cardiac remodeling, and the remodeling changes can be reversed. Furthermore, in the early stages of recovery, cardiac remodeling may be intensified. Finally, compared with the LV, the RV is not as easily reversed. Cardiac remodeling pathways, such as, HDAC4, ERK1/2, LC3-II, and AMPK were involved in the process. PMID:27445861
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Sciammarella, M G; Fragasso, G; Gerundini, P; Maffioli, L; Cappelletti, A; Margonato, A; Savi, A; Chierchia, S
1992-12-01
The ability of 99Tcm-methoxyisobutylisonitrile (MIBI) single photon emission tomography (SPET) to detect myocardial ischaemia and necrosis was assessed in 56 patients (45 male, 11 female, aged 55 +/- 5 years), with clinically recognized ischaemic heart disease (IHD). All underwent coronary angiography (CA) and left ventriculography (LV). SPET images were obtained at rest and at peak exercise (Modified Bruce) 90 min after injection of 99Tcm-MIBI (650-850 MBq). Data were acquired in 30 min over 180 degrees (from 45 degrees RAO to 45 degrees LPO) with no correction for attenuation, using a 64 x 64 matrix. The presence of persistent (P) or reversible (R) perfusion defects (PD) was then correlated to the resting and exercise ECG and to the results of CA and LV. Of the 56 patients, 34 had reversible underperfusion (RPD), 46 persistent underperfusion (PPD) and 31 had both. The occurrence of RPD correlated well with the occurrence of exercise-induced ST segment depression and/or angina (27 patients of 34 patients, 79%) and with the presence of significant coronary artery disease (CAD) (33 of 44, 73%). In 45 of 46 patients (98%) PPD corresponded to akinetic or severely hypokinetic segments (LV) usually explored by ECG leads exhibiting diagnostic Q waves (42 of 46 patients, 91%). The scan was normal both at rest and after stress in four of 11 patients with no CAD, and in two of 45 patients with CAD. Finally, an abnormal resting scan was seen in seven of 11 patients with normal coronary arteries, of whom six had regional wall motion abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
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NASA Technical Reports Server (NTRS)
Komamura, K.; Shannon, R. P.; Pasipoularides, A.; Ihara, T.; Lader, A. S.; Patrick, T. A.; Bishop, S. P.; Vatner, S. F.
1992-01-01
We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition.
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Sharif, Dawod; Matanis, Wisam; Sharif-Rasslan, Amal; Rosenschein, Uri
2016-10-01
Myocardial stunning is responsible for partially reversible left ventricular (LV) systolic dysfunction after successful primary percutaneous coronary intervention (PPCI) in patients with acute ST-elevation myocardial infarction (STEMI). To test the hypothesis that early coronary blood flow (CBF) to LV systolic function ratios, as an equivalent to LV stunning index (SI), predict recovery of LV systolic function after PPCI in patients with acute STEMI. Twenty-four patients with acute anterior STEMI who had successful PPCI were evaluated and compared to 96 control subjects. Transthoracic echocardiography with measurement of LV ejection fraction (EF), LV, and left anterior descending (LAD) coronary artery area wall-motion score index (WMSI) as well as Doppler sampling of LAD blood velocities, early after PPCI and 5 days later, were performed. SI was evaluated as the early ratio of CBF parameters in the LAD to LV systolic function parameters. Early SI-LVEF well predicted late LVEF (r=.51, P<.01) and the change in LVEF (r=.48, P<.017). Early SI-LVMSI predicted well late LVEF (r=.56, P<.006) and the change in LVEF (r=.46, P<.028). Early SI-LADWMSI predicted late LVEF (r=.44, P<.028). Other SI indices measured as other LAD-CBF to LV systolic function parameters were not predictive of late LV systolic function. LV stunning indices measured as early LAD flow to LVEF, LVWMSI, and LADWMSI ratios well predicted late LVEF and the change in LVEF. Thus, greater early coronary artery flow to LV systolic function parameter ratios predict a better improvement in late LV systolic function after PPCI. © 2016, Wiley Periodicals, Inc.
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Cellular entry via an actin and clathrin-dependent route is required for Lv2 restriction of HIV-2.
Harrison, I P; McKnight, A
2011-06-20
Lv2 is a human factor that restricts infection of some HIV-2 viruses after entry into particular target cells. HIV-2 MCR is highly susceptible to Lv2 whereas HIV-2 MCN is not. The block is after reverse transcription but prior to nuclear entry. The viral determinants for this restriction have been mapped to the HIV-2 envelope and the capsid genes. Our model of Lv2 restriction suggests that the route taken into a cell is important in determining whether a productive infection occurs. Here we characterised the infectious routes used by MCN and MCR using chemical compounds and molecular techniques to distinguish between potential pathways. Our results suggest that susceptible MCR can enter restrictive HeLa(CD4) cells via two pathways; a clathrin/AP2 mediated endocytic route that is sensitive to Lv2 restriction and an alternative, non-clathrin mediated route, which results in more efficient infection. Copyright © 2011 Elsevier Inc. All rights reserved.
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Ashikaga, Hiroshi; Leclercq, Christophe; Wang, Jiangxia; Kass, David A.; McVeigh, Elliot R.
2010-01-01
Background Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics. Methods and Results In dogs with left bundle branch block and pacing-induced heart failure (n=7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity. Conclusions CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT. PMID:20478988
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Teshima, Kenji; Asano, Kazushi; Iwanaga, Koji; Koie, Hiroshi; Uechi, Masami; Kato, Yuka; Kutara, Kenji; Kanno, Nobuyuki; Seki, Mamiko; Edamura, Kazuya; Hasegawa, Atsuhiko; Tanaka, Shigeo
2007-02-01
The left ventricular (LV) Tei index (index of myocardial performance) has been demonstrated to be clinically useful in estimating comprehensive LV function, including the systolic and diastolic performances, in various human cardiac diseases. The purposes of this study were to validate the correlation between the LV Tei index and LV function obtained by cardiac catheterization in healthy dogs, and to evaluate the LV Tei index in dogs with naturally occurring mitral regurgitation (MR). In healthy dogs, the LV Tei index was significantly correlated with the LV peak +dP/dt (r = -0.89) and LV peak -dP/dt (r=0.87). The LV Tei index significantly increased in dogs with MR compared with normal dogs and significantly increased with progressively more severe clinical signs due to heart failure. The elevation of the LV Tei index in dogs with symptomatic MR appears to be associated with shortening of ejection time. The LV Tei index significantly increased with age and was not correlated with heart rate and body weight in normal dogs. In conclusion, our study demonstrated that the LV Tei index was measurable in dogs and not influenced by heart rate and body weight. The LV Tei index significantly increased with the progression of clinical signs in MR dogs. In particular, the elevation of the LV Tei index in dogs with symptomatic MR due to shortening of ejection time may suggest LV systolic dysfunction and the decrement of forward stroke volume.
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Decreased expression of endogenous feline leukemia virus in cat lymphomas: a case control study.
Krunic, Milica; Ertl, Reinhard; Hagen, Benedikt; Sedlazeck, Fritz J; Hofmann-Lehmann, Regina; von Haeseler, Arndt; Klein, Dieter
2015-04-10
Cats infected with exogenous feline leukemia virus (exFeLV) have a higher chance of lymphoma development than uninfected cats. Furthermore, an increased exFeLV transcription has been detected in lymphomas compared to non-malignant tissues. The possible mechanisms of lymphoma development by exFeLV are insertional mutagenesis or persistent stimulation of host immune cells by viral antigens, bringing them at risk for malignant transformation. Vaccination of cats against exFeLV has in recent years decreased the overall infection rate in most countries. Nevertheless, an increasing number of lymphomas have been diagnosed among exFeLV-negative cats. Endogenous feline leukemia virus (enFeLV) is another retrovirus for which transcription has been observed in cat lymphomas. EnFeLV provirus elements are present in the germline of various cat species and share a high sequence similarity with exFeLV but, due to mutations, are incapable of producing infectious viral particles. However, recombination between exFeLV and enFeLV could produce infectious particles. We examined the FeLV expression in cats that have developed malignant lymphomas and discussed the possible mechanisms that could have induced malignant transformation. For expression analysis we used next-generation RNA-sequencing (RNA-Seq) and for validation reverse transcription quantitative PCR (RT-qPCR). First, we showed that there was no expression of exFeLV in all samples, which eliminates the possibility of recombination between exFeLV and enFeLV. Next, we analyzed the difference in expression of three enFeLV genes between control and lymphoma samples. Our analysis showed an average of 3.40-fold decreased viral expression for the three genes in lymphoma compared to control samples. The results were confirmed by RT-qPCR. There is a decreased expression of enFeLV genes in lymphomas versus control samples, which contradicts previous observations for the exFeLV. Our results suggest that a persistent stimulation of host immune cells is not an appropriate mechanism responsible for malignant transformation caused by feline endogenous retroviruses.
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Long-Term Adaptive Servo-Ventilator Treatment Prevents Cardiac Death and Improves Clinical Outcome.
Imamura, Teruhiko; Kinugawa, Koichiro; Nitta, Daisuke; Komuro, Issei
2016-01-01
Adaptive servo-ventilation (ASV) is a recently developed, noninvasive therapeutic tool for the treatment of heart failure (HF). However, the efficacy of ASV therapy in patients with advanced HF remains uncertain, especially as regards its contribution to freedom from cardiac replacement therapy. A total of 85 patients with advanced HF (New York Heart Association [NYHA] class IV 71%, inotrope infusion-dependent 34%) refractory to guideline-directed medical therapy, received ASV therapy, irrespective of sleep-disordered breathing, at our institute between 2008 and 2014. Among these 85 patients, 46 continued ASV therapy for > 1 month (continued group), whereas 39 discontinued the therapy after < 1 month because of intolerance (discontinued group). There were no significant differences in baseline variables between the two groups. Heart rate indicating sympathetic activity, left ventricular (LV) reverse remodeling assessed by LV diastolic diameter, LV ejection fraction, and the grades of mitral and tricuspid regurgitations, HF severity assessed by NYHA class and plasma level of B-type natriuretic peptide, and end-organ dysfunction, improved significantly at 6 months following the initiation of ASV therapy (P < 0.05 for all). All-cause mortality and cardiac death rate were significantly lower during 2-year follow up in the continued group (P < 0.05 for both). In conclusion, ASV is a novel therapeutic tool prior to cardiac replacement therapy in patients with advanced HF and may prolong the period until cardiac replacement therapy becomes necessary.
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Chang, Chin-Chyuan; Chang, Hao-Che; Liu, Kuan-Fu; Cheng, Winton
2016-06-01
Transglutaminases (TGs) play critical roles in blood coagulation, immune responses, and other biochemical functions, which undergo post-translational remodeling such as acetylation, phosphorylation and fatty acylation. Two types of TG have been identified in white shrimp, Litopenaeus vannamei, and further investigation on their potential function was conducted by gene silencing in the present study. Total haemocyte count (THC), differential haemocyte count (DHC), phenoloxidase activity, respiratory bursts (release of superoxide anion), superoxide dismutase activity, transglutaminase (TG) activity, haemolymph clotting time, and phagocytic activity and clearance efficiency to the pathogen Vibrio alginolyticus were measured when shrimps were individually injected with diethyl pyrocarbonate-water (DEPC-H2O) or TG dsRNAs. In addition, haemolymph glucose and lactate, and haemocytes crustin, lysozyme, crustacean hyperglycemic hormone (CHH), transglutaminaseI (TGI), transglutaminaseII (TGII) and clotting protein (CP) mRNA expression were determined in the dsRNA injected shrimp under hypothermal stress. Results showed that TG activity, phagocytic activity and clearance efficiency were significantly decreased, but THC, hyaline cells (HCs) and haemolymph clotting time were significantly increased in the shrimp which received LvTGI dsRNA and LvTGI + LvTGII dsRNA after 3 days. However, respiratory burst per haemocyte was significantly decreased in only LvTGI + LvTGII silenced shrimp. In hypothermal stress studies, elevation of haemolymph glucose and lactate was observed in all treated groups, and were advanced in LvTGI and LvTGI + LvTGII silenced shrimp following exposure to 22 °C. LvCHH mRNA expression was significantly up-regulated, but crustin and lysozyme mRNA expressions were significantly down-regulated in LvTGI and LvTGI + LvTGII silenced shrimp; moreover, LvTGII was significantly increased, but LvTGI was significantly decreased in LvTGI silenced shrimp following exposure to 28 and 22 °C. Knockdown of LvTGI and LvTGI + LvTGII also significantly increased the mortality of L. vannamei challenged with the pathogen V. alginolyticus. The same consequences have been confirmed in LvTGII silenced shrimp in our previous study. These results indicate that LvTGI and LvTGII not only reveal a complementary effect in gene expression levels but also play a key function in the immune defence mechanism of shrimp, by regulating the haemolymph coagulation, immune parameters and immune related gene expression, and in the regulation of carbohydrate metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Disruption of Thiamine Uptake and Growth of Cells by Feline Leukemia Virus Subgroup A
Mendoza, Ramon; Miller, A. Dusty
2013-01-01
Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection. PMID:23269813
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Disruption of thiamine uptake and growth of cells by feline leukemia virus subgroup A.
Mendoza, Ramon; Miller, A Dusty; Overbaugh, Julie
2013-03-01
Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection.
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Klein, Franziska J; Bell, Stephen; Runte, K Elisabeth; Lobel, Robert; Ashikaga, Takamuru; Lerman, Lilach O; LeWinter, Martin M; Meyer, Markus
2016-10-01
Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate. Copyright © 2016 the American Physiological Society.
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Dai, Chen-Cheng; Guo, Bao-Jing; Li, Wen-Xiu; Xiao, Yan-Yan; Jin, Mei; Han, Lin; Sun, Jing-Ping; Yu, Cheuk-Man; Dong, Jian-Zeng
2013-11-01
Emerging evidence suggests that significant left ventricular dysfunction may arise in right-sided septal or paraseptal accessory pathways (APs) with Wolff-Parkinson-White syndrome, even in the absence of recurrent or incessant tachycardia. During 1 year and 9 months, we identified four consecutive female children with median age of 8 years diagnosed as having dilated cardiomyopathy (DCM) combined with overt right-sided APs several years ago. Incessant or recurrent tachycardia as the cause of DCM could be excluded. Anti-heart failure chemotherapy did not produce satisfactory effects. The patients underwent radiofrequency ablations (RFCAs). This report describes the clinical and echocardiographic characteristics of the cases before and after the ablation. Dyssynchronous ventricular contraction was observed in all patients. The locations of the APs were the right-sided anteroseptum and the free wall (n = 2 each). All patients received successful RFCAs. Their physical activities and growth improved greatly, and the echocardiographic data demonstrated that their left ventricular (LV) contraction recovered to synchrony shortly after the ablation and that their LV function recovered to normal gradually during the follow-up. A causal relationship between overt ventricular preexcitation and the development of DCM is supported by the complete recovery of LV function and reversed LV remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was probably the crucial mechanism. Not only right-sided septal or paraseptal but also free wall overt APs may induce LV dysfunction and even DCM. AP-induced DCM is an indication for ablation with a good prognosis.
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Effects of Obesity on Cardiovascular Hemodynamics, Cardiac Morphology, and Ventricular Function.
Alpert, Martin A; Omran, Jad; Bostick, Brian P
2016-12-01
Obesity produces a variety of hemodynamic alterations that may cause changes in cardiac morphology which predispose to left and right ventricular dysfunction. Various neurohormonal and metabolic alterations commonly associated with obesity may contribute to these abnormalities of cardiac structure and function. These changes in cardiovascular hemodynamics, cardiac morphology, and ventricular function may, in severely obese patients, predispose to heart failure, even in the absence of other forms of heart disease (obesity cardiomyopathy). In normotensive obese patients, cardiac involvement is commonly characterized by elevated cardiac output, low peripheral vascular resistance, and increased left ventricular (LV) end-diastolic pressure. Sleep-disordered breathing may lead to pulmonary arterial hypertension and, in association with left heart failure, may contribute to elevation of right heart pressures. These alterations, in association with various neurohormonal and metabolic abnormalities, may produce LV hypertrophy; impaired LV diastolic function; and less commonly, LV systolic dysfunction. Many of these alterations are reversible with substantial voluntary weight loss.
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Tibayan, Frederick A; Lai, David T M; Timek, Tomasz A; Dagum, Paul; Liang, David; Zasio, Mary K; Daughters, George T; Miller, D Craig; Ingels, Neil B
2003-05-01
Functional mitral regurgitation (FMR) is increasingly recognized as a left ventricular (LV) disease. Dilated cardiomyopathy (DCM) is commonly accompanied by FMR and reduction of LV torsion. Therapeutic targets for DCM include LV size reduction, altered LV shape, elimination of MR, and increasing LV torsion. It was hypothesized that, in addition to increasing LV size, DCM with FMR would alter normal LV shape and reduce and alter the direction of principal strains across the LV wall. This hypothesis was tested by measuring changes in epicardial and endocardial 2-D principal strains and regional radii of curvature accompanying tachycardia-induced cardiomyopathy in ovine hearts. Radio-opaque marker arrays were implanted into the left ventricle of eight sheep, including one subepicardial triangle and one subendocardial triangle in the anterior wall of the left ventricle. At one week postoperatively, biplane videofluoroscopy was used to determine marker dynamics. Rapid ventricular pacing was then instituted until FMR and signs of heart failure developed, and fluoroscopy was repeated. Circumferential LV radii of curvature were determined from marker triplets. DCM changed the normal epicardial oval LV cross-section to a more circular configuration. The endocardium maintained its normal circular shape as the left ventricle dilated. Deformations of the triangles from end-diastole to end-systole were determined, and the magnitude and direction of 2-D principal strains calculated. DCM was associated with decreased magnitude of both epicardial (-0.095 +/- 0.055 versus -0.040 +/- 0.032, p = 0.006) and endocardial (-0.117 +/- 0.047 versus -0.073 +/- 0.037, p = 0.023) principal strains. DCM reduced the angle of epicardial but not endocardial principal strain. DCM with FMR is associated with LV dilation, circularization of the normally oval equatorial circumferential LV epicardium, transmural reduction in principal strain, and decrease in angle of principal epicardial strain. These changes contribute to a reduction in the net torsional moment and may guide the development of reverse remodeling procedures for the dilated, failing ventricle with FMR.
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Solis, Jorge; Levine, Robert A; Johnson, Benjamin; Guerrero, J Luis; Handschumacher, Mark D; Sullivan, Suzanne; Lam, Kaitlyn; Berlin, Jason; Braithwaite, Gavin J C; Muratoglu, Orhun K; Vlahakes, Gus J; Hung, Judy
2010-10-01
Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8±1.2 to1.8±1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (30.3±5.7 to 25.9±4.6 mm, P=0.02), tenting volume (1.8±0.7 to 1.4±0.5 mL, P=0.01), and leaflet closure area (8.8±1.3 cm(2)to 7.6±1.3 cm(2), P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41±3% versus 40±3%, P=NS), end-systolic elastance, τ (82±36 ms to 72±26, P=NS), or LV stiffness coefficient (0.05±0.04 to 0.03±0.01). PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position.
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van Bommel, Rutger J.; Tanaka, Hidekazu; Delgado, Victoria; Bertini, Matteo; Borleffs, Carel Jan Willem; Ajmone Marsan, Nina; Holzmeister, Johannes; Ruschitzka, Frank; Schalij, Martin J.; Bax, Jeroen J.; Gorcsan, John
2010-01-01
Aims Current criteria for cardiac resynchronization therapy (CRT) are restricted to patients with a wide QRS complex (>120 ms). Overall, only 30% of heart failure patients demonstrate a wide QRS complex, leaving the majority of heart failure patients without this treatment option. However, patients with a narrow QRS complex exhibit left ventricular (LV) mechanical dyssynchrony, as assessed with echocardiography. To further elucidate the possible beneficial effect of CRT in heart failure patients with a narrow QRS complex, this two-centre, non-randomized observational study focused on different echocardiographic parameters of LV mechanical dyssynchrony reflecting atrioventricular, interventricular and intraventricular dyssynchrony, and the response to CRT in these patients. Methods and results A total of 123 consecutive heart failure patients with a narrow QRS complex (<120 ms) undergoing CRT was included at two centres. Several widely accepted measures of mechanical dyssynchrony were evaluated: LV filling ratio (LVFT/RR), LV pre-ejection time (LPEI), interventricular mechanical dyssynchrony (IVMD), opposing wall delay (OWD), and anteroseptal posterior wall delay with speckle tracking (ASPWD). Response to CRT was defined as a reduction ≥15% in left ventricular end-systolic volume at 6 months follow-up. Measures of dyssynchrony can frequently be observed in patients with a narrow QRS complex. Nonetheless, for LVFT/RR, LPEI, and IVMD, presence of predefined significant dyssynchrony is <20%. Significant intraventricular dyssynchrony is more widely observed in these patients. With receiver operator characteristic curve analyses, both OWD and ASPWD demonstrated usefulness in predicting response to CRT in narrow QRS patients with a cut-off value of 75 and 107 ms, respectively. Conclusion Mechanical dyssynchrony can be widely observed in heart failure patients with a narrow QRS complex. In particular, intraventricular measures of mechanical dyssynchrony may be useful in predicting LV reverse remodelling at 6 months follow-up in heart failure patients with a narrow QRS complex, but with more stringent cut-off values than currently used in ‘wide’ QRS patients. PMID:20864484
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Levy, Philip T; El-Khuffash, Afif; Patel, Meghna D; Breatnach, Colm R; James, Adam T; Sanchez, Aura A; Abuchabe, Cristina; Rogal, Sarah R; Holland, Mark R; McNamara, Patrick J; Jain, Amish; Franklin, Orla; Mertens, Luc; Hamvas, Aaron; Singh, Gautam K
2017-07-01
The aim of this study was to determine the maturational changes in systolic ventricular strain mechanics by two-dimensional speckle-tracking echocardiography in extremely preterm neonates from birth to 1 year of age and discern the impact of common cardiopulmonary abnormalities on the deformation measures. In a prospective multicenter study of 239 extremely preterm infants (<29 weeks gestation at birth), left ventricular (LV) global longitudinal strain (GLS) and global longitudinal systolic strain rate (GLSRs), interventricular septal wall (IVS) GLS and GLSRs, right ventricular (RV) free wall longitudinal strain and strain rate, and segmental longitudinal strain in the RV free wall, LV free wall, and IVS were serially measured on days 1, 2, and 5 to 7, at 32 and 36 weeks postmenstrual age, and at 1 year corrected age (CA). Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately. In uncomplicated preterm infants (n = 103 [48%]), LV GLS and GLSRs remained unchanged from days 5 to 7 to 1 year CA (P = .60 and P = .59). RV free wall longitudinal strain, RV free wall longitudinal strain rate, and IVS GLS and GLSRs significantly increased over the same time period (P < .01 for all measures). A significant base-to-apex (highest to lowest) segmental longitudinal strain gradient (P < .01) was seen in the RV free wall and a reverse apex-to-base gradient (P < .01) in the LV free wall. In infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]), RV free wall longitudinal strain and IVS GLS were significantly lower (P < .01), LV GLS and GLSRs were similar (P = .56), and IVS segmental longitudinal strain persisted as an RV-dominant base-to-apex gradient from 32 weeks postmenstrual age to 1 year CA. This study tracks the maturational patterns of global and regional deformation by two-dimensional speckle-tracking echocardiography in extremely preterm infants from birth to 1 year CA. The maturational patterns are ventricular specific. Bronchopulmonary dysplasia and pulmonary hypertension leave a negative impact on RV and IVS strain, while LV strain remains stable. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
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Shen, Jian-Bing; Shutt, Robin; Agosto, Mariela; Pappano, Achilles; Liang, Bruce T
2009-04-01
Binary cardiac transgenic (Tg) overexpression of P2X(4) receptors (P2X(4)R) improved the survival of the cardiomyopathic calsequestrin (CSQ) mice. Here we studied the mechanism of rescue using binary P2X(4)R/CSQ Tg and CSQ Tg mice as models. Cellular and intact heart properties were determined by simultaneous sarcomere shortening (SS) and Ca(2+) transients in vitro and echocardiography in vivo. Similar to a delay in death, binary mice exhibited a slowed heart failure progression with a greater left ventricular (LV) fractional shortening (FS) and thickness and a concomitant lesser degree of LV dilatation in both systole and diastole at 8 or 12 wk. By 16 wk, binary hearts showed similarly depressed FS and thinned out LV and equal enlargement of LV as did 12-wk-old CSQ hearts. Binary cardiac myocytes showed higher peak basal cell shortening (CS) and SS as well as greater basal rates of shortening and relaxation than did the CSQ myocytes at either 8 or 12 wk. Similar data were obtained in comparing the Ca(2+) transient. At 16 wk, binary myocytes were like the 12-wk-old CSQ myocytes with equally depressed CS, SS, and Ca(2+) transient. CSQ myocytes were longer than myocytes from wild-type and binary mice at 12 wk of age. At 16 wk, the binary myocyte length increased to that of the 12-wk-old CSQ myocyte, parallel to LV dilatation. The data suggest a unique mechanism, which involves a reversal of cardiac myocyte dysfunction and a delay in heart failure progression. It represents an example of targeting the abnormal failing myocyte in treating heart failure.
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Kappus, Rebecca M.; Ranadive, Sushant M.; Yan, Huimin; Lane, Abbi D.; Cook, Marc D.; Hall, Grenita; Harvey, I. Shevon; Wilund, Kenneth R.; Woods, Jeffrey A.; Fernhall, Bo
2012-01-01
Objective Left ventricular end systolic pressure (LV ESP) is important in assessing left ventricular performance. LV ESP is usually derived from prediction equations. It is unknown whether these equations are accurate at rest or following exercise in a young, healthy population. Design We compared measured LV ESP versus LV ESP values from the prediction equations at rest, 15 minutes and 30 minutes following peak aerobic exercise in 60 participants. Methods LV ESP was obtained by applanation tonometry at rest, 15 minutes post and 30 minutes post peak cycle exercise. Results Measured LV ESP was significantly lower (p<0.05) at all time points in comparison to the two calculated values. Measured LV ESP decreased significantly from rest at both the post15 and post30 time points (p<0.05) and changed differently in comparison to the calculated values (significant interaction; p<0.05). The two LV ESP equations were also significantly different from each other (p<0.05) and changed differently over time (significant interaction; p<0.05). Conclusions These data indicate that the two prediction equations commonly used did not accurately predict either resting or post exercise LV ESP in a young, healthy population. Thus, LV ESP needs to be individually determined in young healthy participants. Non-invasive measurement through applanation tonometry appears to allow for a more accurate determination of LV ESP. PMID:22721862
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Pavlovic, Melanie; Koehler, Nina; Anton, Martina; Dinkelmeier, Anna; Haase, Maren; Stellberger, Thorsten; Busch, Ulrich; Baiker, Armin E
2017-08-01
The purpose of the described method is the detection of and differentiation between RNA and DNA of human immunodeficiency virus (HIV)-derived lentiviral vectors (LV) in cell culture supernatants and swab samples. For the analytical surveillance of genetic engineering, operations methods for the detection of the HIV-1-based LV generations are required. Furthermore, for research issues, it is important to prove the absence of LV particles for downgrading experimental settings in terms of the biosafety level. Here, a quantitative polymerase chain reaction method targeting the long terminal repeat U5 subunit and the start sequence of the packaging signal ψ is described. Numerous controls are included in order to monitor the technical procedure.
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Petit-Eisenmann, Hélène; Epailly, Eric; Velten, Michel; Radojevic, Jelena; Eisenmann, Bernard; Kremer, Hélène; Kindo, Michel
2016-12-01
The impact of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) for aortic stenosis on exercise capacity remains controversial. The aim of this study was to analyze the long-term impact of PPM after mechanical AVR on maximal oxygen uptake (VO 2max ). The study included 75 patients who had undergone isolated mechanical AVR for aortic stenosis with normal left ventricular (LV) function between 1994 and 2012. Their functional capacity was evaluated on average 4.6 years after AVR by exercise testing, including measurement of their VO 2max , and by determining their New York Heart Association functional class and Short Form-36 score. Two groups were defined by measuring the patients' indexed effective orifice area (iEOA) by transthoracic echocardiography: a PPM group (iEOA < 0.85 cm 2 /m 2 ) and a no-PPM group (iEOA ≥ 0.85 cm 2 /m 2 ). PPM was present in 37.0% of the patients. The percentage of the predicted VO 2max achieved was significantly lower in the PPM group (86.7 ± 19.5% vs 97.5 ± 23.0% in the no-PPM group; P = 0.04). Compared with the no-PPM group, the PPM group contained fewer patients in New York Heart Association functional class I and their mean Short Form-36 physical component summary score was significantly lower. The mean transvalvular gradient was significantly higher in the PPM group than in the no-PPM group (P < 0.001). Systolic and diastolic function and LV mass had normalized in both groups. PPM is associated in the long term with moderate but significant impairment of functional capacity, despite optimal LV reverse remodelling and normalization of LV systolic and diastolic function. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Grupper, Avishay; Zhao, Yanjun M; Sajgalik, Pavol; Joyce, Lyle D; Park, Soon J; Pereira, Naveen L; Stulak, John M; Burnett, John C; Edwards, Brooks S; Daly, Richard C; Kushwaha, Sudhir S; Schirger, John A
2016-06-01
Neurohormonal blockade drug therapy (NHBDT) is the cornerstone therapy in heart failure (HF) management for promoting reverse cardiac remodeling and improving outcomes. It's utility in left ventricular assist device (LVAD) supported patients remains undefined. Sixty-four patients who received continuous flow LVAD at our institution were retrospectively reviewed and divided into 2 groups: no-NHBDT group (n = 33) received LVAD support only and NHBDT group (n = 31) received concurrent NHBDT based on the clinical judgment of the attending physicians. Cardiac remodeling (echocardiographic parameters and biomarkers) and clinical outcome (functional status, HF-related hospital readmissions, and mortality) data were collected. A statistically significant increase in ejection fraction, decrease in LV end-diastolic diameter index and LV mass index, and a sustained reduction in N-terminal pro B-type natriuretic peptide (NTproBNP) were observed in the NHBDT group at 6 months after LVAD implant (p <0.05). NHBDT-treated patients experienced significantly greater improvement in New York Heart Association functional classification and 6-minute-walk distance throughout the study. The combined end point of cardiovascular death or HF hospitalization was significantly reduced in patients receiving NHBDT (p = 0.013) associated primarily with a 12.1% absolute reduction in HF-related hospitalizations (p = 0.046). In conclusion, NHBDT in LVAD-supported patients is associated with a significant reversal in adverse cardiac remodeling and a reduction in morbidity and mortality compared with LVAD support alone. Copyright © 2016 Elsevier Inc. All rights reserved.
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Pinkham, Maximilian I.; Loftus, Michael T.; Amirapu, Satya; Guild, Sarah-Jane; Quill, Gina; Woodward, William R.; Habecker, Beth A.
2017-01-01
Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for 4 wk before receiving bilateral RDx or sham RDx. After additional 3 wk, left ventricular (LV) function was assessed, and ventricular sympathetic nerve fiber density was determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue norepinephrine content (nerve fiber density in the LV of MI+sham RDx hearts was 0.31 ± 0.05% vs. 1.00 ± 0.10% in sham MI+sham RDx group, P < 0.05), and RDx significantly increased ventricular sympathetic innervation (0.76 ± 0.14%, P < 0.05) and tissue norepinephrine content. MI was associated with an increase in fibrosis of the noninfarcted ventricular myocardium, which was attenuated by RDx. RDx improved LV ejection fraction and end-systolic and -diastolic areas when compared with pre-RDx levels. This is the first study to show an interaction between renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart. PMID:28052866
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Bernard, Anne; Donal, Erwan; Leclercq, Christophe; Schnell, Frédéric; Fournet, Maxime; Reynaud, Amélie; Thebault, Christophe; Mabo, Philippe; Daubert, J-Claude; Hernandez, Alfredo
2015-06-01
The mechanisms of improvement of left ventricular (LV) function with cardiac resynchronization therapy (CRT) are not yet elucidated. The aim of this study was to describe a new tool based on automatic quantification of the integrals of regional longitudinal strain signals and evaluate changes in LV strain distribution after CRT. This was a retrospective observational study of 130 patients with heart failure before CRT device implantation and after 3 to 6 months of follow-up. Integrals of regional longitudinal strain signals (from the beginning of the cardiac cycle to strain peak [IL,peak] and to the instant of aortic valve closure [IL,avc]) were analyzed retrospectively with custom-made algorithms. Response to CRT was defined as a decrease in LV end-systolic volume of ≥15%. Responders (61%) and nonresponders (39%) showed similar baseline values of regional IL,peak and IL,avc. At follow-up, significant improvements of midlateral IL,peak and of midlateral IL,avc were noted only in responders. Midlateral IL,avc showed a relative increase of 151 ± 276% in responders, whereas a decrease of 33 ± 69% was observed in nonresponders. The difference between IL,avc and IL,peak (representing wasted energy of the LV myocardium) of the lateral wall showed a relative change of -59 ± 103% in responders between baseline and CRT, whereas in nonresponders, the relative change was 21 ± 113% (P = .009). Strain integrals revealed changes between baseline and CRT in the lateral wall, demonstrating the beneficial effects of CRT on LV mechanics with favorable myocardial reverse remodeling. Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
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Lee, Byung Kook; Jeung, Kyung Woon; Choi, Sung Soo; Park, Sang Wook; Yun, Seong Woo; Lee, Sung Min; Kim, Nan Yeol; Heo, Tag; Min, Yong Il
2015-02-01
Ischaemic contracture compromises the haemodynamic effectiveness of cardiopulmonary resuscitation and resuscitability. 2,3-Butanedione monoxime (BDM) reduced ischaemic contracture by inhibiting actin-myosin crossbridge formation in an isolated heart model. We investigated the effects of BDM on ischaemic contracture and resuscitation outcomes in a pig model of out-of-hospital cardiac arrest (OHCA). After 15min of untreated ventricular fibrillation, followed by 8min of basic life support, 16 pigs were randomised to receive either 2mlkg(-1) of BDM solution (25gl(-1)) or 2mlkg(-1) of saline during advanced cardiac life support (ACLS). During the ACLS, the control group showed an increase in left ventricular (LV) wall thickness from 10.0mm (10.0-10.8) to 13.0mm (13.0-13.0) and a decrease in LV chamber area from 8.13cm(2) (7.59-9.29) to 7.47cm(2) (5.84-8.43). In contrast, the BDM group showed a decrease in the LV wall thickness from 10mm (9.0-10.8) to 8.5mm (7.0-9.8) and an increase in the LV chamber area from 9.86cm(2) (7.22-12.39) to 12.15 cm(2) (8.02-14.40). Mixed model analyses of the LV wall thickness and LV chamber area revealed significant group effects and group-time interactions. Spontaneous circulation was restored in four (50%) animals in the control group and in eight (100%) animals in the BDM group (p=0.077). All the resuscitated animals survived during an intensive care period of 4h. BDM administered during cardiopulmonary resuscitation reversed ischaemic contracture in a pig model of OHCA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Saracoglu, Erhan; Kılıç, Salih; Vuruşkan, Ertan; Düzen, Irfan; Çekici, Yusuf; Kuzu, Zülfiye; Yıldırım, Arafat; Küçükosmanoğlu, Mehmet; Çetin, Mustafa
2018-06-05
Few studies have shown the direct effect of familial hypercholesterolemia (FH) on myocardial systolic function. Studies focused on heterozygote FH patients but not homozygote ones, and they did not perform genetic analyses. We aimed to evaluate all types of patients with FH using the potentially more sensitive speckle tracking echocardiography (STE) technique to identify early left ventricular (LV) dysfunction. Genetic analyses of patients with FH were conducted for LDL-receptor, PCSK9, and ApoB100. Nine homozygote, two compound heterozygote, and 82 heterozygote FH patients and 85 healthy subjects were prospectively studied. Longitudinal and circumferential strain measurements and conventional echocardiography findings were obtained. LV ejection fractions were similar for all (homozygote, heterozygote, and control) groups. The LV average longitudinal strain (aLS) and average circumferential strain (aCS) levels were significantly reduced in the homozygote and heterozygote groups when compared with the controls (for aLS, P = .008 (<.001); for aCS, P =< .001). A significant inverse correlation was found between LDL-C levels and LS (P < .001, r = .728) and CS (P < .001, r = .642) for all FH patients. This study demonstrates the potential of using systolic strain values obtained using 2D STE for determining lipotoxicity in the myocardium owing to hypercholesterolemia. Our study found that cardiac functions of homozygote patients who had the highest cholesterol levels were disrupted at very early ages. Therefore, starting lipid reduction treatment and early reverse LV remodelling therapy at early ages may be beneficial for high-risk patients. © 2018 Wiley Periodicals, Inc.
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Dai, Bo; Huang, Wei; Xu, Meifeng; Millard, Ronald W.; Gao, Mei Hua; Hammond, H. Kirk; Menick, Donald R.; Ashraf, Muhammad; Wang, Yigang
2012-01-01
Objectives The purpose of this study was to assess the effect of scar tissue composition on engraftment of progenitor cells into infarcted myocardium. Background Scar tissue formation after myocardial infarction creates a barrier that severely compromises tissue regeneration, limiting potential functional recovery. Methods In vitro: A tricell patch (Tri-P) was created from peritoneum seeded and cultured with induced pluripotent stem cell–derived cardiomyocytes, endothelial cells, and mouse embryonic fibroblasts. The expression of fibrosis-related molecules from mouse embryonic fibroblasts and infarcted heart was measured by Western blot and quantitative reverse transcriptase polymerase chain reaction. In vivo: A Tri-P was affixed over the entire infarcted area 7 days after myocardial infarction in mice overexpressing adenylyl cyclase 6 (AC6). Engraftment efficiency of progenitor cells in hearts of AC6 mice was compared with that of control wild-type (WT) mice using a combination of in vivo bioluminescence imaging, post-mortem ex vivo tissue analysis, and the number of green fluorescent protein–positive cells. Echocardiography of left ventricular (LV) function was performed weekly. Hearts were harvested for analysis 4 weeks after Tri-P application. Mouse embryonic fibroblasts were stimulated with forskolin before an anoxia/reoxygenation protocol. Fibrosis-related molecules were analyzed. Results In AC6 mice, infarcted hearts treated with Tri-P showed significantly higher bioluminescence imaging intensity and numbers of green fluorescent protein–positive cells than in WT mice. LV function improved progressively in AC6 mice from weeks 2 to 4 and was associated with reduced LV fibrosis. Conclusions Application of a Tri-P in AC6 mice resulted in significantly higher induced pluripotent stem cell engraftment accompanied by angiomyogenesis in the infarcted area and improvement in LV function. PMID:22051336
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NASA Technical Reports Server (NTRS)
Pu, M.; Griffin, B. P.; Vandervoort, P. M.; Stewart, W. J.; Fan, X.; Cosgrove, D. M.; Thomas, J. D.
1999-01-01
Although alteration in pulmonary venous flow has been reported to relate to mitral regurgitant severity, it is also known to vary with left ventricular (LV) systolic and diastolic dysfunction. There are few data relating pulmonary venous flow to quantitative indexes of mitral regurgitation (MR). The object of this study was to assess quantitatively the accuracy of pulmonary venous flow for predicting MR severity by using transesophageal echocardiographic measurement in patients with variable LV dysfunction. This study consisted of 73 patients undergoing heart surgery with mild to severe MR. Regurgitant orifice area (ROA), regurgitant stroke volume (RSV), and regurgitant fraction (RF) were obtained by quantitative transesophageal echocardiography and proximal isovelocity surface area. Both left and right upper pulmonary venous flow velocities were recorded and their patterns classified by the ratio of systolic to diastolic velocity: normal (>/=1), blunted (<1), and systolic reversal (<0). Twenty-three percent of patients had discordant patterns between the left and right veins. When the most abnormal patterns either in the left or right vein were used for analysis, the ratio of peak systolic to diastolic flow velocity was negatively correlated with ROA (r = -0.74, P <.001), RSV (r = -0.70, P <.001), and RF (r = -0.66, P <.001) calculated by the Doppler thermodilution method; values were r = -0.70, r = -0.67, and r = -0.57, respectively (all P <.001), for indexes calculated by the proximal isovelocity surface area method. The sensitivity, specificity, and predictive values of the reversed pulmonary venous flow pattern for detecting a large ROA (>0.3 cm(2)) were 69%, 98%, and 97%, respectively. The sensitivity, specificity, and predictive values of the normal pulmonary venous flow pattern for detecting a small ROA (<0.3 cm(2)) were 60%, 96%, and 94%, respectively. However, the blunted pattern had low sensitivity (22%), specificity (61%), and predictive values (30%) for detecting ROA of greater than 0.3 cm(2) with significant overlap with the reversed and normal patterns. Among patients with the blunted pattern, the correlation between the systolic to diastolic velocity ratio was worse in those with LV dysfunction (ejection fraction <50%, r = 0.23, P >.05) than in those with normal LV function (r = -0.57, P <.05). Stepwise linear regression analysis showed that the peak systolic to diastolic velocity ratio was independently correlated with RF (P <.001) and effective stroke volume (P <.01), with a multiple correlation coefficient of 0.71 (P <.001). In conclusion, reversed pulmonary venous flow in systole is a highly specific and reliable marker of moderately severe or severe MR with an ROA greater than 0.3 cm(2), whereas the normal pattern accurately predicts mild to moderate MR. Blunted pulmonary venous flow can be seen in all grades of MR with low predictive value for severity of MR, especially in the presence of LV dysfunction. The blunted pulmonary venous flow pattern must therefore be interpreted cautiously in clinical practice as a marker for severity of MR.
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Kappus, Rebecca M; Ranadive, Sushant M; Yan, Huimin; Lane, Abbi D; Cook, Marc D; Hall, Grenita; Harvey, I Shevon; Wilund, Kenneth R; Woods, Jeffrey A; Fernhall, Bo
2013-01-01
Left ventricular end systolic pressure (LV ESP) is important in assessing left ventricular performance and is usually derived from prediction equations. It is unknown whether these equations are accurate at rest or following exercise in a young, healthy population. Measured LV ESP vs. LV ESP values from the prediction equations were compared at rest, 15 min and 30 min following peak aerobic exercise in 60 participants. LV ESP was obtained by applanation tonometry at rest, 15 min post and 30 min post peak cycle exercise. Measured LV ESP was significantly lower (p<0.05) at all time points in comparison to the two calculated values. Measured LV ESP decreased significantly from rest at both the post15 and post30 time points (p<0.05) and changed differently in comparison to the calculated values (significant interaction; p<0.05). The two LV ESP equations were also significantly different from each other (p<0.05) and changed differently over time (significant interaction; p<0.05). The two commonly used prediction equations did not accurately predict either resting or post exercise LV ESP in a young, healthy population. Thus, LV ESP needs to be individually determined in young, healthy participants. Non-invasive measurement through applanation tonometry appears to allow for a more accurate determination of LV ESP. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
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Liu, Jiayou; O'Connor, Thomas; Beall, Melissa; Chandrashekar, Ramaswamy; Lappin, Michael
2016-01-01
Feline leukemia virus (FeLV) is a potentially life-threatening oncogenic retrovirus. The p27 viral core protein is produced by the virus in infected feline cells, is found in the cytoplasm in several blood cells and can be free in the serum and plasma. ELISA or particle-based immunoassay are commonly used to detect the presence of the p27 core protein in samples obtained from blood. The objective of this study was to compare the performance of several in-clinic tests: the SNAP Feline Triple Test (IDEXX Laboratories), the WITNESS FeLV-FIV Test (Zoetis) and the VetScan Feline FeLV/FIV Rapid Test (Abaxis). The sample population (100 positive, 105 negative samples) consisted of serum and plasma samples submitted to IDEXX's worldwide reference laboratory for feline retrovirus testing. Virus isolation and reverse transcriptase PCR results were not available and so samples were judged to be positive or negative based on the results of the ViraCHEK FeLV (Zoetis) microtiter plate assay. The percentage of samples positive and negative for FeLV p27 antigen using the three in-clinic tests compared with the ViraCHEK method were as follows: IDEXX Feline Triple (positive 98.0%, negative 100%); Zoetis WITNESS (positive 79.0%, negative 97.1%); Abaxis VetScan (positive 73.0%, negative 97.1%). The SNAP Feline Triple Test demonstrated a high level of agreement for FeLV-positive and FeLV-negative samples when assessed in this model. Results of FeLV assays can vary among tests.
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Spada, Eva; Perego, Roberta; Sgamma, Elena Assunta; Proverbio, Daniela
2018-02-01
Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are among the most important feline infectious diseases worldwide. This retrospective study investigated survival times and effects of selected predictor factors on survival time in a population of owned pet cats in Northern Italy testing positive for the presence of FIV antibodies and FeLV antigen. One hundred and three retrovirus-seropositive cats, 53 FIV-seropositive cats, 40 FeLV-seropositive cats, and 10 FIV+FeLV-seropositive cats were included in the study. A population of 103 retrovirus-seronegative age and sex-matched cats was selected. Survival time was calculated and compared between retrovirus-seronegative, FIV, FeLV and FIV+FeLV-seropositive cats using Kaplan-Meier survival analysis. Cox proportional-hazards regression analysis was used to study the effect of selected predictor factors (male gender, peripheral blood cytopenia as reduced red blood cells - RBC- count, leukopenia, neutropenia and lymphopenia, hypercreatininemia and reduced albumin to globulin ratio) on survival time in retrovirus-seropositive populations. Median survival times for seronegative cats, FIV, FeLV and FIV+FeLV-seropositive cats were 3960, 2040, 714 and 77days, respectively. Compared to retrovirus-seronegative cats median survival time was significantly lower (P<0.000) in FeLV and FIV+FeLV-seropositive cats. Median survival time in FeLV and FIV+FeLV-seropositive cats was also significant lower (P<0.000) when compared to FIV-seropositive cats. Hazard ratio of death in FeLV and FIV+FeLV-seropositive cats being respectively 3.4 and 7.4 times higher, in comparison to seronegative cats and 2.3 and 4.8 times higher in FeLV and FIV+FeLV-seropositive cats as compared to FIV-seropositive cats. A Cox proportional-hazards regression analysis showed that FIV and FeLV-seropositive cats with reduced RBC counts at time of diagnosis of seropositivity had significantly shorter survival times when compared to FIV and FeLV-seropositive cats with normal RBC counts at diagnosis. In summary, FIV-seropositive status did not significantly affect longevity of cats in this study, unlike FeLV and FIV+FeLV-seropositivity. Reduced RBC counts at time of FIV and FeLV diagnosis could impact negatively on the longevity of seropositive cats and therefore blood counts should always be evaluated at diagnosis and follow-up of retrovirus-seropositive cats. Copyright © 2017 Elsevier B.V. All rights reserved.
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Gorska-Flipot, I; Huang, M; Cantin, M; Rassart, E; Massé, G; Jolicoeur, P
1992-01-01
BL/VL3 radiation leukemia virus (RadLV) is a thymotropic, highly leukemogenic murine leukemia virus (MuLV) which is unable to replicate in vitro in mouse fibroblasts. We have previously reported that the U3 long terminal repeat region of its genome is responsible for this block (E. Rassart, Y. Paquette, and P. Jolicoeur, J. Virol. 62:3840-3848, 1988). By using hybrids of permissive and resistant cells infected with BL/VL3 RadLV or fibrotropic MuLV, we found that the resistant phenotype was dominant. Investigation to determine at which step of the virus cycle the block operates revealed that integration, transcription, and translation of the BL/VL3 viral genome occurred at normal levels in nonpermissive cells. The BL/VL3 RadLV Pr65gag proteins made in nonpermissive cells were also myristylated and located at the membrane, and the levels of their cleaved products were similar to those of fibrotropic MuLV. However, processing of BL/VL3 RadLV Pr85env was impaired in nonpermissive cells. Virions were not released into the culture medium of nonpermissive cells, as measured by reverse transcriptase activity and by content in p30 or gp70 protein and as documented by lower levels of budding particles seen by electron microscopy. These results indicate that BL/VL3 RadLV replication is blocked at a late stage of the virus cycle, i.e., at virion assembly. Interestingly, these BL/VL3 RadLV-infected nonpermissive fibroblasts were resistant to superinfection by fibrotropic Moloney MuLV, and this resistance also occurred at a late step of the Moloney virus cycle. Since this block is dominant, it appears that the U3 long terminal repeat region of the BL/VL3 viral genome has the ability to induce a cellular suppressor factor(s), thus bringing intracellular immunity against itself and against other ecotropic MuLVs. Images PMID:1433513
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dos Santos, Simone Nascimento; Henz, Benhur Davi; Zanatta, André Rodrigues; Barreto, José Roberto; Loureiro, Kelly Bianca; Novakoski, Clarissa; dos Santos, Marcus Vinícius Nascimento; Giuseppin, Fabio F.; Oliveira, Edna Maria; Leite, Luiz Roberto
2014-01-01
Background Left ventricular (LV) diastolic dysfunction is associated with new-onset atrial fibrillation (AF), and the estimation of elevated LV filling pressures by E/e' ratio is related to worse outcomes in patients with AF. However, it is unknown if restoring sinus rhythm reverses this process. Objective To evaluate the impact of AF ablation on estimated LV filling pressure. Methods A total of 141 patients underwent radiofrequency (RF) ablation to treat drug-refractory AF. Transthoracic echocardiography was performed 30 days before and 12 months after ablation. LV functional parameters, left atrial volume index (LAVind), and transmitral pulsed and mitral annulus tissue Doppler (e' and E/e') were assessed. Paroxysmal AF was present in 18 patients, persistent AF was present in 102 patients, and long-standing persistent AF in 21 patients. Follow-up included electrocardiographic examination and 24-h Holter monitoring at 3, 6, and 12 months after ablation. Results One hundred seventeen patients (82.9%) were free of AF during the follow-up (average, 18 ± 5 months). LAVind reduced in the successful group (30.2 mL/m2 ± 10.6 mL/m2 to 22.6 mL/m2 ± 1.1 mL/m2, p < 0.001) compared to the non-successful group (37.7 mL/m2 ± 14.3 mL/m2 to 37.5 mL/m2 ± 14.5 mL/m2, p = ns). Improvement of LV filling pressure assessed by a reduction in the E/e' ratio was observed only after successful ablation (11.5 ± 4.5 vs. 7.1 ± 3.7, p < 0.001) but not in patients with recurrent AF (12.7 ± 4.4 vs. 12 ± 3.3, p = ns). The success rate was lower in the long-standing persistent AF patient group (57% vs. 87%, p = 0.001). Conclusion Successful AF ablation is associated with LA reverse remodeling and an improvement in LV filling pressure. PMID:25590928
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Zlatanovic, Maja; Tadic, Marijana; Celic, Vera; Ivanovic, Branislava; Stevanovic, Ana; Damjanov, Nemanja
2017-01-01
We aimed to determine left ventricular (LV) and right ventricular (RV) structure, function and mechanics, as well as heart rate variability (HRV), and their relationship, in patients with systemic sclerosis (SSc). The study included 41 SSc patients and 30 age-matched healthy volunteers. All the patients underwent clinical examination, serological tests, pulmonary function testing, 24-h Holter monitoring and complete two-dimensional echocardiography including strain analysis. The parameters of LV structure (interventricular septum thickness and LV mass index) and RV structure (RV wall thickness) were significantly higher in SSc patients. LV and RV diastolic function (estimated by mitral and tricuspid E/e' ratio) was significantly impaired in SSc group comparing with the healthy controls. LV and RV longitudinal function was significantly deteriorated in SSc patients. LV circumferential strain was also significantly lower in SSc group, whereas LV radial strain was similar between the observed groups. All parameters of time and frequency domain of HRV were decreased in SSc patients. LV and RV cardiac remodeling parameters, particularly diastolic function and longitudinal strain, were associated with HRV indices without regard to the main demographic or the clinical and echocardiographic characteristics. Rodnan Skin Score was also independently associated with biventricular cardiac remodeling in SSc patients. LV and RV structure, function and mechanics, as well as autonomic nervous function, were significantly impaired in SSc patients. There is the significant association between biventricular cardiac remodeling and autonomic function in these patients, which could be useful for their everyday clinical assessment.
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Subclinical atherosclerosis in obese adolescents with normal left ventricular function.
Abdel-Wahab, Amina M; Atwa, Hoda A; El-Eraky, Azza Z; El-Aziz, Mohamed A
2011-09-01
To assess the impact of obesity on carotid intima media thickness and left ventricular (LV) mass in obese adolescents. The study included 52 obese adolescents (mean age 14.16+/-2.64 years) and 52 healthy adolescents who served as a control group (mean age 12+/-2.3 years), who were attended the outpatient clinic at Suez Canal University Hospital, Ismailia, Egypt. The study population was submitted for medical history, clinical examination, laboratory investigations (fasting blood sugar and lipid profile), and echocardiographic examination of LV mass and dimensions. Assessment of carotid intima-media thickness was carried out by using carotid duplex. All children had normal LV function. Obese adolescents had a significant increase in total cholesterol, triglyceride, LDL-C, and low HDL-C compared to the control group. Also, there was a significant increase in blood pressure, carotid intima media thickness, LV mass, and LV mass index. There was a significant correlation between BMI and dyslipidemia, blood pressure, carotid intima/media thickness, LV mass, and posterior wall thickness. Carotid intima-media thickness had a significant correlation with increased LDL-C and low HDL-C, blood pressure, LV mass, and posterior wall thickness. Obesity in childhood and adolescents is associated with subclinical atherosclerosis. Although obese children had no LV dysfunction, yet there are LV structure changes.
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NASA Technical Reports Server (NTRS)
Qin, Jian Xin; Shiota, Takahiro; McCarthy, Patrick M.; Asher, Craig R.; Hail, Melanie; Agler, Deborah A.; Popovic, Zoran B.; Greenberg, Neil L.; Smedira, Nicholas G.; Starling, Randall C.;
2003-01-01
BACKGROUND: Left ventricular (LV) reconstruction surgery leads to early improvement in LV function in ischemic cardiomyopathy (ICM) patients. This study was designed to evaluate the impact of mitral valve (MV) repair associated with LV reconstruction on LV function 1-year after surgery in ICM patients assessed by real-time 3-dimensional echocardiography (3DE). METHODS AND RESULTS: Sixty ICM patients who underwent the combination surgery (LV reconstruction in 60, MV repair in 30, and revascularization in 52 patients) were studied. Real-time 3DE was performed and LV volumes were obtained at baseline, discharge, 6-month and >or=12-month follow-up. Reduction in end-diastolic volumes (EDV) by 29% and in end-systolic volumes by 38% were demonstrated immediately after surgery and remained at subsequent follow-up (P<0.0001). The LV ejection fraction significantly increased by about 10% at discharge and was maintained >or=12-month (P<0.0001). Although the LV volumes were significantly larger in patients with MV repair before surgery (EDV, 235+/-87 mL versus 193+/-67 mL, P<0.05), they were similar to LV volumes of the patients without MV repair at subsequent follow-ups. However, the EDV increased from 139+/-24 mL to 227+/-79 mL (P<0.01) in 7 patients with recurrent mitral regurgitation (MR). Improvement in New York Heart Association functional class occurred in 81% patients during late follow-up. CONCLUSIONS: Real-time 3DE demonstrates that LV reconstruction provides significant reduction in LV volumes and improvement in LV function which is sustained throughout the 1-year follow-up with 84% cardiac event free survival. If successful, MV repair may prevent LV redilation, while recurrent MR is associated with increased LV volumes.
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Carter-Storch, Rasmus; Møller, Jacob E; Christensen, Nicolaj L; Irmukhadenov, Akhmadjon; Rasmussen, Lars M; Pecini, Redi; Øvrehus, Kristian A; Søndergård, Eva V; Marcussen, Niels; Dahl, Jordi S
2017-12-01
Severe aortic stenosis (AS) most often presents with reduced aortic valve area (<1 cm 2 ), normal stroke volume index (≥35 mL/m 2 ), and either high mean gradient (≥40 mm Hg; normal-flow high-gradient AS) or low mean gradient (normal-flow low-gradient [NFLG] AS). The benefit of aortic valve replacement (AVR) among NFLG patients is controversial. We compared the impact of NFLG condition on preoperative left ventricular (LV) remodeling and myocardial fibrosis and postoperative remodeling and symptomatic benefit. Eighty-seven consecutive patients with reduced aortic valve area and normal stroke volume index undergoing AVR underwent echocardiography, magnetic resonance imaging, a 6-minute walk test, and measurement of natriuretic peptides before and 1 year after AVR. Myocardial fibrosis was assessed from magnetic resonance imaging. Patients were stratified as NFLG or normal-flow high-gradient. In total, 33 patients (38%) had NFLG. Before AVR, they were characterized by similar symptom burden but less severe AS measured by aortic valve area index (0.50±0.09 versus 0.40±0.08 cm 2 /m 2 ; P <0.0001), lower LV mass index (74±18 versus 90±26 g/m 2 ; P =0.01), but the same degree of myocardial fibrosis. After AVR, NFLG had a smaller reduction in LV mass index (-3±10 versus -±18 g/m 2 ; P <0.0001) and a smaller reduction in natriuretic peptides. Both groups experienced similar symptomatic improvement. Normal-flow high-gradient condition independently predicted change in LV mass index. Patients with NFLG had less severe AS and LV remodeling than patients with normal-flow high-gradient. Furthermore, NFLG patients experienced less reverse remodeling but the same symptomatic benefit. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02316587. © 2017 American Heart Association, Inc.
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Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng
Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension.
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Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng
2016-01-01
Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension. PMID:28008249
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Favorable Changes in Cardiac Geometry and Function Following Gastric Bypass Surgery
Owan, Theophilus; Avelar, Erick; Morley, Kimberly; Jiji, Ronny; Hall, Nathaniel; Krezowski, Joseph; Gallagher, James; Williams, Zachary; Preece, Kevin; Gundersen, Nancy; Strong, Michael B.; Pendleton, Robert C.; Segerson, Nathan; Cloward, Tom V.; Walker, James M.; Farney, Robert J.; Gress, Richard E.; Adams, Ted D.; Hunt, Steven C.; Litwin, Sheldon E.
2013-01-01
Objectives The objective of this study was to test the hypothesis that gastric bypass surgery (GBS) would favorably impact cardiac remodeling and function. Background GBS is increasingly used to treat severe obesity, but there are limited outcome data. Methods We prospectively studied 423 severely obese patients undergoing GBS and a reference group of severely obese subjects that did not have surgery (n = 733). Results At a 2-year follow up, GBS subjects had a large reduction in body mass index compared with the reference group (−15.4 ± 7.2 kg/m2 vs. −0.03 ± 4.0 kg/m2; p < 0.0001), as well as significant reductions in waist circumference, systolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, and insulin resistance. High-density lipoprotein cholesterol increased. The GBS group had reductions in left ventricular (LV) mass index and right ventricular (RV) cavity area. Left atrial volume did not change in GBS but increased in reference subjects. In conjunction with reduced chamber sizes, GBS subjects also had increased LV midwall fractional shortening and RV fractional area change. In multivariable analysis, age, change in body mass index, severity of nocturnal hypoxemia, E/E', and sex were independently associated with LV mass index, whereas surgical status, change in waist circumference, and change in insulin resistance were not. Conclusions Marked weight loss in patients undergoing GBS was associated with reverse cardiac remodeling and improved LV and RV function. These data support the use of bariatric surgery to prevent cardiovascular complications in severe obesity. PMID:21292133
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Masaki, Mitsuru; Mano, Toshiaki; Eguchi, Akiyo; Fujiwara, Shohei; Sugahara, Masataka; Hirotani, Shinichi; Tsujino, Takeshi; Komamura, Kazuo; Koshiba, Masahiro; Masuyama, Tohru
2016-11-01
Left ventricular (LV) diastolic dysfunction is associated with hypertension and hyperuricemia. However, it is not clear whether the L- and N-type calcium channel blocker will improve LV diastolic dysfunction through the reduction of uric acid. The aim of this study was to investigate the effects of anti-hypertensive therapy, the L- and N-type calcium channel blocker, cilnidipine or the L-type calcium channel blocker, amlodipine, on left atrial reverse remodeling and uric acid in hypertensive patients. We studied 62 patients with untreated hypertension, randomly assigned to cilnidipine or amlodipine for 48 weeks. LV diastolic function was assessed with the left atrial volume index (LAVI), mitral early diastolic wave (E), tissue Doppler early diastolic velocity (E') and the ratio (E/E'). Serum uric acid levels were measured before and after treatment. After treatment, systolic and diastolic blood pressures equally dropped in both groups. LAVI, E/E', heart rate and uric acid levels decreased at 48 weeks in the cilnidipine group but not in the amlodipine group. The % change from baseline to 48 weeks in LAVI, E wave, E/E' and uric acid levels were significantly lower in the cilnidipine group than in the amlodipine group. Larger %-drop in uric acid levels were associated with larger %-reduction of LAVI (p < 0.01). L- and N-type calcium channel blocker but not L-type calcium channel blocker may improve LV diastolic function in hypertensive patients, at least partially through the decrease in uric acid levels.
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Bell, Susan P; Adkisson, Douglas W; Lawson, Mark A; Wang, Li; Ooi, Henry; Sawyer, Douglas B; Kronenberg, Marvin W
2014-08-27
Left ventricular (LV) energy supply-demand imbalance is postulated to cause "energy starvation" and contribute to heart failure (HF) in nonischemic dilated cardiomyopathy (NIDCM). Using cardiac magnetic resonance (CMR) and [(11)C] acetate positron emission tomography (PET), we evaluated LV perfusion and oxidative metabolism in NIDCM and the effects of spironolactone on LV supply-demand relations. Twelve patients with NIDCM underwent CMR and PET at baseline and after ≥6 months of spironolactone therapy added to a standard HF regimen. The myocardial perfusion reserve index (MPRI) was calculated after gadolinium injection during adenosine, as compared to rest. The monoexponential clearance rate of [(11)C] acetate (kmono) was used to calculate the work metabolic index (WMI), an index of LV mechanical efficiency, and kmono/RPP (rate-pressure product), an index of energy supply/demand. At baseline, the subendocardium was hypoperfused versus the subepicardium (median MPRI, 1.63 vs. 1.80; P<0.001), but improved to 1.80 (P<0.001) after spironolactone. The WMI increased (P=0.001), as did kmono/RPP (P=0.003). These improvements were associated with reverse remodeling, increased LV ejection fraction, and decreases in LV mass and systolic wall stress (all P<0.002). NIDCM is associated with subendocardial hypoperfusion and impaired myocardial oxidative metabolism, consistent with energy starvation. Antifailure therapy improves parameters of energy starvation and is associated with augmented LV performance. http://www.clinicaltrials.gov/ Unique identifier: ID NCT00574119. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
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Evaluation of left ventricular function in anesthetized patients using femoral artery dP/dt(max).
De Hert, Stefan G; Robert, Dominique; Cromheecke, Stefanie; Michard, Frédéric; Nijs, Jan; Rodrigus, Inez E
2006-06-01
The purpose of this study was to compare dP/dt(max) estimated from a femoral artery pressure tracing to left ventricular (LV) dP/dt(max) during various alterations in myocardial loading and contractile function. Seventy patients scheduled for elective coronary artery bypass surgery. All patients were instrumented with a high-fidelity LV catheter, a pulmonary artery catheter, and a femoral arterial catheter. In 40 patients, hemodynamic measurements were performed before and after passive leg raising and before and after calcium administration (5 mg/kg); and in 30 other patients, hemodynamic measurements were performed before and after dobutamine infusion (5 microg/kg/min over 10 minutes). LV and femoral dP/dt(max) were significantly correlated (r = 0.82, p < 0.001), but femoral dP/dt(max) systematically underestimated LV dP/dt(max) (bias = -361 +/- 96 mmHg/s). Passive leg raising induced significant increases in central venous pressure and LV end-diastolic pressure, but femoral dP/dt(max), stroke volume, and LV dP/dt(max) remained unaltered. Calcium administration induced significant and marked increases in LV dP/dt(max) (23% +/- 9%) and femoral dP/dt(max) (37% +/- 14%) associated with a significant increase in stroke volume (9% +/- 2%). Dobutamine infusion also induced significant and marked increases in LV dP/dt(max) (25% +/- 8%) and femoral dP/dt(max) (35% +/- 12%) associated with a significant increase in stroke volume (14% +/- 3%). Overall, a very close linear relationship (r = 0.93) and a good agreement (bias = -5 +/- 17 mmHg/s) were found between changes in LV dP/dt(max) and changes in femoral dP/dt(max). A very close relationship was also observed between changes in LV dP/dt(max) and changes in femoral dP/dt(max) during each intervention (leg raising, calcium administration, and dobutamine infusion). Femoral dP/dt(max) underestimated LV dP/dt(max), but changes in femoral dP/dt(max) accurately reflected changes in LV dP/dt(max) during various interventions.
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Choi, Ung Lim; Park, Jae-Hyeong; Sun, Byung Joo; Oh, Jin Kyung; Seong, Seok Woo; Lee, Jae-Hwan; Choi, Si Wan; Jeong, Jin-Ok; Kwon, In Sun; Seong, In-Whan
2018-05-01
Left ventricular (LV) apical thrombus is a clinically important complication which can cause systemic embolization in patients with anterior acute myocardial infarction (AMI). Systolic dysfunction has been a risk factor for developing LV apical thrombus in AMI patients. However, the role of diastolic dysfunction in the development of LV apical thrombus in these patients is still unknown. We performed this study to evaluate whether diastolic dysfunction can influence the development of LV apical thrombus in anterior AMI patients. We retrospectively analyzed all consecutive anterior AMI patients with available echocardiographic images within 1 month from January 2005 to April 2016. After gathering clinical characteristics from their medical records, systolic and diastolic functions were analyzed from digitally stored echocardiographic images. We included a total of 1045 patients (748 males, mean age 64 ± 12 years) with anterior AMI, and 494 (47%) were diagnosed as STEMI. The incidence of LV apical thrombus was 3.3% (34/1045). The LV apical thrombus group had larger LV diastolic dimension, larger LV diastolic and systolic volumes, and lower LVEF than the no LV thrombus group. The LV apical thrombus group showed higher mitral E velocity over mitral annular E' velocity ratio, an indicator of LV end-diastolic pressure (P < 0.001). In the LV apical thrombus group, the incidence of grade 2 diastolic dysfunction (32 vs 12%, P = 0.001) and grade 3 diastolic dysfunction (26 vs 2%, P < 0.001) were significantly higher than in the no LV apical thrombus group. The presence of more than grade 2 diastolic dysfunction, LVEF and presence of LV apical aneurysm were statistically significant factors associated with LV apical thrombus after the multivariate analysis. In conclusion, along with LV systolic dysfunction and LV apical aneurysm, LV diastolic dysfunction was also related with the presence of LV apical thrombus in patients with anterior AMI.
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Ooka, Junichi; Tanaka, Hidekazu; Hatani, Yutaka; Hatazawa, Keiko; Matsuzoe, Hiroki; Shimoura, Hiroyuki; Sano, Hiroyuki; Sawa, Takuma; Motoji, Yoshiki; Mochizuki, Yasuhide; Ryo-Koriyama, Keiko; Matsumoto, Kensuke; Fukuzawa, Koji; Hirata, Ken-Ichi
2017-10-21
Although right ventricular (RV) pacing is the only effective treatment for patients with symptomatic bradycardia, it creates left ventricular (LV) dyssynchrony, which can induce LV dysfunction and heart failure. The current criterion for consideration of cardiac resynchronization therapy (CRT) is LV ejection fraction (LVEF) ≤ 35%, but indication for CRT in patients required for RV pacing with LVEF > 35% remains unclear.We studied 40 patients, all LVEF ≥ 35%, who had undergone implantable cardioverter-defibrillator implantation with RV pacing < 5%. Echocardiography was performed at baseline and during RV pacing. LV dyssynchrony was defined as anteroseptal-to-posterior wall delay from the mid-LV short-axis view using two-dimensional speckle-tracking radial strain (significant: ≥ 130 ms). Patients were divided into two groups based on baseline LVEF: normal LVEF ( ≥ 50%; n = 20) and mildly reduced LVEF (35-50%; n = 20).LVEF and LV dyssynchrony in patients with mildly reduced LVEF deteriorated significantly during RV pacing compared to those in patients with normal LVEF. Moreover, changes in LV dyssynchrony during RV pacing significantly correlated with changes in LVEF (r = -0.44, P < 0.01). Multivariate logistic regression analysis showed that baseline LVEF was the only independent predictor and baseline LVEF < 48% predictive of significant LV dyssynchrony during RV pacing.The extent of RV pacing-induced LV dysfunction may be associated with baseline LV function. These adverse effects on patients with mildly reduced LVEF of 35-50% and indications for RV pacing due to bradycardia can thus be prevented by CRT.
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de Castro, Fernanda Luz; Junqueira, Dennis Maletich; de Medeiros, Rúbia Marília; da Silva, Tailene Rabello; Costenaro, Jamile Girardi; Knak, Marcus Braga; de Matos Almeida, Sabrina Esteves; Campos, Fabrício Souza; Roehe, Paulo Michel; Franco, Ana Cláudia
2014-10-01
Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are widely distributed retroviruses that infect domestic cats (Felis catus). Restriction factors are proteins that have the ability to hamper retroviruses' replication and are part of the conserved mechanisms of anti-viral immunity of mammals. The APOBEC3 protein family is the most studied class of restriction factors; they are cytidine deaminases that generate hypermutations in provirus DNA during reverse transcription, thus causing hypermutations in the viral genome, hindering virus replication. One of the feline APOBEC3 genes, named APOBEC3H, encodes two proteins (APOBEC3H and APOBEC3CH). In other mammals, APOBEC3H single-nucleotide polymorphisms (SNPs) can alter the stability and cellular localization of the encoded protein, thus influencing its subcellular localization and reducing its anti-viral effect. In cats, the association of APOBEC3H SNPs with susceptibility to retroviral infections was not yet demonstrated. Therefore, this study aimed the investigation on the variability of APOBEC3H and the possible association with FIV/FeLV infections. DNA obtained from whole blood of fifty FIV- and/or FeLV-infected cats and fifty-nine FIV- and/or FeLV-uninfected cats were used as templates to amplify two different regions of the APOBEC3H, with subsequent sequencing and analysis. The first region was highly conserved among all samples, while in the second, six single-nucleotide variation points were identified. One of the SNPs, A65S (A65I), was significantly correlated with the susceptibility to FIV and/or FeLV infections. On the other hand, the haplotype analysis showed that the combination "GGGGCC" was positively correlated with the lack of FIV and/or FeLV infections. Our results indicate that, as previously shown in other mammals, variability of restriction factors may contribute to susceptibility of domestic cats to retroviral infections; however, these results should be confirmed by more extensive analysis and in vitro experiments. Copyright © 2014 Elsevier B.V. All rights reserved.
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Jonsson, C B; Roth, M J
1993-01-01
Retroviral integrases mediate site-specific endonuclease and transesterification reactions in the absence of exogenous energy. The basis for the sequence specificity in these integrase-viral DNA recognition processes is unknown. Structural analogs of the disintegration substrate were made to analyze the disintegration reaction mechanism for the Moloney murine leukemia virus (M-MuLV) integrase (IN). Modifications in the target DNA portion of the disintegration substrate decreased enzymatic activity, while substitution of the highly conserved CA in the viral long terminal repeat portion had no effect on activity. The role of the His-Cys finger region in catalysis was addressed by N-ethylmaleimide (NEM) modification of the cysteine residues of M-MuLV IN as well as by mutations. Both integration activities, 3' processing, and strand transfer, were completely inhibited by NEM modification of M-MuLV IN, while disintegration activity was only partially sensitive. However, structural analogs of the disintegration substrates that were modified in the target DNA and had the conserved CA removed were not active with NEM-treated M-MuLV IN. In addition, mutants made in the His-Cys region of M-MuLV IN were examined and found to also be completely blocked in integration but not disintegration activity. These data suggest that the domains of M-MuLV IN that are required for the forward integration reaction substrate differ from those required for the reverse disintegration reaction substrate. Images PMID:8350412
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Decreased left ventricular torsion in patients with isolated mitral stenosis.
Kirilmaz, B; Asgun, F; Saygi, S; Ercan, E
2015-02-01
Left ventricular (LV) torsion is a sensitive indicator of myocardial contractility and cardiac structure, and has recently been recognized as a sensitive indicator of cardiac performance. The aim of our study was to assess the effect of isolated mitral stenosis on LV torsion. We enrolled 19 patients with isolated mitral stenosis and 19 age- and gender-matched healthy subjects in the study. All patients had a normal sinus rhythm. All study subjects underwent two-dimensional echocardiography. Basal and apical LV rotations and LV torsion were evaluated using speckle-tracking echocardiography. Demographic characteristics, basic echocardiographic measures of LV ejection fraction, LV wall thickness, and LV mass index were similar between the two groups. The degrees of LV torsion (11.3 ± 4.7, 15.4 ± 4.9°, p=0.014) and LV basal rotation (- 3.7 ± 1.9, - 6.5 ± 2.1°, p< 0.001) were significantly decreased in the mitral stenosis group. There was a moderate positive correlation between mitral valve area and LV torsion (r=0.531, p=0.019). We showed significant reductions in LV torsion and LV basal rotation in patients with mitral valve stenosis. Structural and anatomical changes occurring during the progression of mitral stenosis may be responsible for these impaired movements.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tan Wenyong; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan; Liu Dong
Purpose: We investigated whether the heart could be replaced by the anterior myocardial territory (AMT) as the organ at risk (OAR) in intensity-modulated radiotherapy (IMRT) of the breast for patients with left-sided breast cancer. Methods and Materials: Twenty-three patients with left-sided breast cancer who received postoperative radiation after breast-conserving surgery were studied. For each patient, we generated five IMRT plans including heart (H), left ventricle (LV), AMT, LV+AMT, and H+LV as the primary OARs, respectively, except both lungs and right breast, which corresponded to IMRT(H), IMRT(LV), IMRT(AMT), IMRT(LV+AMT), and IMRT(H+LV). For the planning target volumes and OARs, the parameters ofmore » dose-volume histograms were compared. Results: The homogeneity index, conformity index, and coverage index were not compromised significantly in IMRT(AMT), IMRT(LV) and IMRT(LV+ AMT), respectively, when compared with IMRT(H). The mean dose to the heart, LV, and AMT decreased 5.3-21.5% (p < 0.05), 19.9-29.5% (p < 0.05), and 13.3-24.5% (p < 0.05), respectively. Similarly, the low (e.g., V5%), middle (e.g., V20%), and high (e.g., V30%) dose-volume of the heart, LV, and AMT decreased with different levels. The mean dose and V10% of the right lung increased by 9.2% (p < 0.05) and 27.6% (p < 0.05), respectively, in IMRT(LV), and the mean dose and V5% of the right breast decreased significantly in IMRT(AMT) and IMRT(LV+AMT). IMRT(AMT) was the preferred plan and was then compared with IMRT(H+LV); the majority of dose-volume histogram parameters of OARs including the heart, LV, AMT, both lungs, and the right breast were not statistically different. However, the low dose-volume of LV increased and the middle dose-volume decreased significantly (p < 0.05) in IMRT(AMT). Also, those of the right lung (V10%, V15%) and right breast (V5%, V10%) decreased significantly (p < 0.05). Conclusions: The AMT may replace the heart as the OAR in left-sided breast IMRT after breast-conserving surgery to decrease the radiation dose to the heart.« less
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Kong, Jing-Rong; Wei, Wei; Liang, Qing-Jian; Qiao, Xue-Li; Kang, Huan; Liu, Yuan; Wang, Wei-Na
2018-05-01
It is well known that PI3K regulates various processes in mammalian cells by generating a secondary messenger that later activates AKT. However, its innate immune function in crustaceans remains unclear. We report the characterization of Litopenaeus vannamei PI3K (LvPI3K) for investigating how PI3K participates in the innate immunity of crustaceans. Full-length LvPI3K cDNA was 3357 bp long, with a 3222 bp open reading frame (ORF) that encodes a putative protein of 1292 amino acids. The PI3K catalytic domain (PI3Kc) of LvPI3K was found to be rather conserved when the PI3Ks from other species were analyzed. The LvPI3K protein was shown to be localized to the cytoplasm of Drosophila S2 cells, while LvPI3K mRNA was ubiquitously expressed in healthy L. vannamei, with the highest expression found in hemolymph. A dual luciferase reporter gene assay demonstrated that LvPI3K overexpression activated the promoter of antibacterial peptide LvPEN4 in a dose-dependent manner. However, the addition of PDTC, a specific inhibitor of NF-κB, suppressed the LvPI3K-induced LvPEN4 promoter activation. Moreover, Vibrio alginolyticus challenge induced a rapid up-regulation of LvPI3K expression. Further experiments showed that LvPI3K silencing in shrimp challenged with V. alginolyticus significantly increased Vibrio number, ROS production and DNA damage in the hemolymph, as well as significantly decreased total hemocyte count. The mRNA levels of certain molecules related to LvPI3K signaling, such as LvAKT and LvPEN4, also decreased following LvPI3K silencing. Taken together, these results suggest that LvPI3K regulates the downstream signal component LvPEN4 and functions in V. alginolyticus resistance. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Arena, Gabriella D.; Ramos-González, Pedro L.; Nunes, Maria A.; Ribeiro-Alves, Marcelo; Camargo, Luis E. A.; Kitajima, Elliot W.; Machado, Marcos A.; Freitas-Astúa, Juliana
2016-01-01
Leprosis is a serious disease of citrus caused by Citrus leprosis virus C (CiLV-C, genus Cilevirus) whose transmission is mediated by false spider mites of the genus Brevipalpus. CiLV-C infection does not systemically spread in any of its known host plants, thus remaining restricted to local lesions around the feeding sites of viruliferous mites. To get insight into this unusual pathosystem, we evaluated the expression profiles of genes involved in defense mechanisms of Arabidopsis thaliana and Citrus sinensis upon infestation with non-viruliferous and viruliferous mites by using reverse-transcription qPCR. These results were analyzed together with the production of reactive oxygen species (ROS) and the appearance of dead cells as assessed by histochemical assays. After interaction with non-viruliferous mites, plants locally accumulated ROS and triggered the salicylic acid (SA) and jasmonate/ethylene (JA/ET) pathways. ERF branch of the JA/ET pathways was highly activated. In contrast, JA pathway genes were markedly suppressed upon the CiLV-C infection mediated by viruliferous mites. Viral infection also intensified the ROS burst and cell death, and enhanced the expression of genes involved in the RNA silencing mechanism and SA pathway. After 13 days of infestation of two sets of Arabidopsis plants with non-viruliferous and viruliferous mites, the number of mites in the CiLV-C infected Arabidopsis plants was significantly higher than in those infested with the non-viruliferous ones. Oviposition of the viruliferous mites occurred preferentially in the CiLV-C infected leaves. Based on these results, we postulated the first model of plant/Brevipalpus mite/cilevirus interaction in which cells surrounding the feeding sites of viruliferous mites typify the outcome of a hypersensitive-like response, whereas viral infection induces changes in the behavior of its vector. PMID:27933078
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Siminiak, Tomasz; Wu, Justina C.; Haude, Michael; Hoppe, Uta C.; Sadowski, Jerzy; Lipiecki, Janusz; Fajadet, Jean; Shah, Amil M.; Feldman, Ted; Kaye, David M.; Goldberg, Steven L.; Levy, Wayne C.; Solomon, Scott D.; Reuter, David G.
2012-01-01
Aims Functional mitral regurgitation (FMR) contributes to morbidity and mortality in heart failure (HF) patients. The aim of this study was to determine whether percutaneous mitral annuloplasty could safely and effectively reduce FMR and yield durable long-term clinical benefit. Methods and results The impact of mitral annuloplasty (Carillon Mitral Contour System) was evaluated in HF patients with at least moderate FMR. Patients in whom the device was placed then acutely recaptured for clinical reasons served as a comparator group. Quantitative measures of FMR, left ventricular (LV) dimensions, New York Heart Association (NYHA) class, 6 min walk distance (6MWD), and quality of life were assessed in both groups up to 12 months. Safety and key functional data were assessed in the implanted cohort up to 24 months. Thirty-six patients received a permanent implant; 17 had the device recaptured. The 30-day major adverse event rate was 1.9%. In contrast to the comparison group, the implanted cohort demonstrated significant reductions in FMR as represented by regurgitant volume [baseline 34.5 ±11.5 mL to 17.4 ±12.4 mL at 12 months (P < 0.001)]. There was a corresponding reduction in LV diastolic volume [baseline 208.5 ±62.0 mL to 178.9 ±48.0 mL at 12 months (P =0.015)] and systolic volume [baseline 151.8 ±57.1 mL to 120.7 ±43.2 mL at 12 months (P =0.015)], compared with progressive LV dilation in the comparator. The 6MWD markedly improved for the implanted patients by 102.5 ±164 m at 12 months (P =0.014) and 131.9 ±80 m at 24 months (P < 0.001). Conclusion Percutaneous reduction of FMR using a coronary sinus approach is associated with reverse LV remodelling. Significant clinical improvements persisted up to 24 months. PMID:22613584
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Characterizing Heart Failure in the Ventricular Volume Domain
Kerkhof, Peter LM
2015-01-01
Heart failure (HF) may be accompanied by considerable alterations of left ventricular (LV) volume, depending on the particular phenotype. Two major types of HF have been identified, although heterogeneity within each category may be considerable. All variants of HF show substantially elevated LV filling pressures, which tend to induce changes in LV size and shape. Yet, one type of HF is characterized by near-normal values for LV end-diastolic volume (EDV) and even a smaller end-systolic volume (ESV) than in matched groups of persons without cardiac disease. Furthermore, accumulating evidence indicates that, both in terms of shape and size, in men and women, the heart reacts differently to adaptive stimuli as well as to certain pharmacological interventions. Adjustments of ESV and EDV such as in HF patients are associated with (reverse) remodeling mechanisms. Therefore, it is logical to analyze HF subtypes in a graphical representation that relates ESV to EDV. Following this route, one may expect that the two major phenotypes of HF are identified as distinct entities localized in different areas of the LV volume domain. The precise coordinates of this position imply unique characteristics in terms of the actual operating point for LV volume regulation. Evidently, ejection fraction (EF; equal to 1 minus the ratio of ESV and EDV) carries little information within the LV volume representation. Thus far, classification of HF is based on information regarding EF combined with EDV. Our analysis shows that ESV in the two HF groups follows different patterns in dependency of EDV. This observation suggests that a superior HF classification system should primarily be founded on information embodied by ESV. PMID:25780344
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Meng, Fanjun; Li, Yan; Chi, Wenying; Li, Junfa
2016-07-01
Brain protection by narcotics such as morphine is clinically relevant due to the extensive use of narcotics in the perioperative period. Morphine preconditioning induces neuroprotection in neurons, but it remains uncertain whether microRNA-134 (miR-134) is involved in morphine preconditioning against oxygen-glucose deprivation-induced injuries in primary cortical neurons of mice. The present study examined this issue. After cortical neurons of mice were cultured in vitro for 6 days, the neurons were transfected by respective virus vector, such as lentiviral vector (LV)-miR-control-GFP, LV-pre-miR-134-GFP, LV-pre-miR-134-inhibitor-GFP for 24 hours; after being normally cultured for 3 days again, morphine preconditioning was performed by incubating the transfected primary neurons with morphine (3 μM) for 1 hour, and then neuronal cells were exposed to oxygen-glucose deprivation (OGD) for 1 hour and oxygen-glucose recovery for 12 hours. The neuronal cells survival rate and the amount of apoptotic neurons were determined by MTT assay or TUNEL staining at designated time; and the expression levels of miR-134 were detected using real-time reverse transcription polymerase chain reaction at the same time. The neuronal cell survival rate was significantly higher, and the amount of apoptotic neurons was significantly decreased in neurons preconditioned with morphine before OGD than that of OGD alone. The neuroprotection induced by morphine preconditioning was partially blocked by upregulating miR-134 expression, and was enhanced by downregulating miR-134 expression. The expression of miR-134 was significantly decreased in morphine-preconditioned neurons alone without transfection. By downregulating miR-134 expression, morphine preconditioning protects primary cortical neurons of mice against injuries induced by OGD.
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Right ventricular involution: What can we learn from nature's model of compensated hypertrophy?
Bowen, Megan E; Liu, Xiaoqing; Sundwall, Peter M; Drakos, Stavros G; Li, Dean Y; Selzman, Craig H; McKellar, Stephen H
2018-05-01
Right ventricular (RV) failure (RVF) is a vexing problem facing patients with various disease processes and carries a high mortality. RVF is a poorly understood phenomenon with limited treatment options. In mammalian fetal circulation, the right ventricle is the systemic ventricle. In neonates, however, the left ventricle assumes that role and gradually thickens compared with the right ventricle. This process, known as right ventricular involution (RVI), is poorly understood. We sought to define the time course and identify mechanisms involved in RVI. Wild-type mice were bred and sacrificed on day of life (DOL) 1, 4, 8, 16, and 30 to evaluate left ventricular (LV) and RV wall thickness and apoptosis. A terminal deoxynucleotidyl transferase nick-end labeling assay and RNA sequencing were performed to measure changes during RVI. Morphometric analysis demonstrated the changes in RV and LV wall thickness occurring between DOL 1 and DOL 16 (RV:LV, 0.53:0.44; P = .03). In addition, apoptosis was most active early, with the highest percentage of apoptotic cells on DOL 1 (1.0%) and a significant decrease by DOL 30 (0.23%) (P = .02). Similarly, expression of the proapoptotic genes BCL2l11 and Pawr were increased at DOL 1, and the antiapoptotic genes Nol3 and Naip2 were significantly increased at DOL 30. RVI is a misnomer, but significant changes occur early (by DOL 16) in neonatal mouse hearts. Apoptosis plays a role in RVI, but whether manipulation of apoptotic pathways can prevent or reverse RVI is unknown and warrants further investigation. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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Shan, Siqing; Flowers, Clay; Peltz, Cathy D; Sweet, Heather; Maurer, Norbert; Kwon, Eun-Joo Gina; Krol, Ave; Yuan, Fan; Dewhirst, Mark W
2006-08-01
To quantitatively evaluate the extravasation, accumulation and selectivity to tumor tissues of liposomal vincristine (LV), dorsal skin-fold window chambers on athymic mice with or without LX-1, a human small cell lung cancer, xenograft implants and fluorescent intravital microscopy imaging were used. In vitro studies show that minimal loss of fluorescence marker DiI from liposomes occurs after 4 days of inoculation in murine plasma, and the release profiles of DiI-LV and LV were essentially the same with approximately 40% of the encapsulated vincristine sulfate (VCR) released after 26 h. Significantly faster extravasation of DiI-LV from tumor vessels was shown compared to non-tumor tissue after single dose i.v. administration. The relative interstitial amounts at 60 min (RIA(60)) for tumor and non-tumor tissues were 0.837+/-0.314 and 0.012+/-0.091, respectively (P=0.01). DiI-LV accumulation was significantly higher in tumor than in normal tissue, which continued beyond 48 h. Both DiI-LV and LV showed significant antitumor effects in window chambers and in flank tumors, compared with controls and VLS alone. The preferential extravasation of DiI-LV from tumor vasculature as well as its differential retention in tumor tissue provides the basis for the enhancement in antitumor activity of LV over VCR.
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Fujiwara, Shohei; Komamura, Kazuo; Nakabo, Ayumi; Masaki, Mitsuru; Fukui, Miho; Sugahara, Masataka; Itohara, Kanako; Soyama, Yuko; Goda, Akiko; Hirotani, Shinichi; Mano, Toshiaki; Masuyama, Tohru
2016-02-01
Left ventricular (LV) dyssynchrony is a causal factor in LV dysfunction and thought to be associated with LV twisting motion. We tested whether three-dimensional speckle tracking (3DT) can be used to evaluate the relationship between LV twisting motion and dyssynchrony. We examined 25 patients with sick sinus syndrome who had received dual chamber pacemakers. The acute effects of ventricular pacing on LV wall motion after the switch from atrial to ventricular pacing were assessed. LV twisting motion and dyssynchrony during each pacing mode were measured using 3DT. LV dyssynchrony was calculated from the time to the minimum peak systolic area strain of 16 LV imaging segments. Ventricular pacing increased LV dyssynchrony and decreased twist and torsion. A significant correlation was observed between changes in LV dyssynchrony and changes in torsion (r = -0.65, p < 0.01). Evaluation of LV twisting motion can potentially be used for diagnosing LV dyssynchrony.
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Chi, C; Yu, S-K; Auckle, R; Argyris, A A; Nasothimiou, E; Tountas, C; Aissopou, E; Blacher, J; Safar, M E; Sfikakis, P P; Zhang, Y; Protogerou, A D
2017-10-01
Both brachial blood pressure (BP) level and its variability (BPV) significantly associate with left ventricular (LV) structure and function. Recent studies indicate that aortic BP is superior to brachial BP in the association with LV abnormalities. However, it remains unknown whether aortic BPV better associate with LV structural and functional abnormalities. We therefore aimed to investigate and compare aortic versus brachial BPV, in terms of the identification of LV abnormalities. Two hundred and three participants who underwent echocardiography were included in this study. Twenty-four-hour aortic and brachial ambulatory BP was measured simultaneously by a validated BP monitor (Mobil-O-Graph, Stolberg, Germany) and BPV was calculated with validated formulae. LV mass and LV diastolic dysfunction (LVDD) were evaluated by echocardiography. The prevalence of LV hypertrophy (LVH) and LVDD increased significantly with BPV indices (P⩽0.04) in trend tests. After adjustment to potential confounders, only aortic average real variability (ARV), but not brachial ARV or weighted s.d. (wSD, neither aortic nor brachial) significantly associated with LV mass index (P=0.02). Similar results were observed in logistic regression. After adjustment, only aortic ARV significantly associated with LVH (odds ratio (OR) and 95% confidence interval (CI): 2.28 (1.08, 4.82)). As for LVDD, neither the brachial nor the aortic 24-hour wSD, but the aortic and brachial ARV, associated with LVDD significantly, with OR=2.28 (95% CI: (1.03, 5.02)) and OR=2.36 (95% CI: (1.10, 5.05)), respectively. In summary, aortic BPV, especially aortic ARV, seems to be superior to brachial BPV in the association of LV structural and functional abnormalities.
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Systolic and Diastolic Left Ventricular Mechanics during and after Resistance Exercise.
Stöhr, Eric J; Stembridge, Mike; Shave, Rob; Samuel, T Jake; Stone, Keeron; Esformes, Joseph I
2017-10-01
To improve the current understanding of the impact of resistance exercise on the heart, by examining the acute responses of left ventricular (LV) strain, twist, and untwisting rate ("LV mechanics"). LV echocardiographic images were recorded in systole and diastole before, during and immediately after (7-12 s) double-leg press exercise at two intensities (30% and 60% of maximum strength, one-repetition maximum). Speckle tracking analysis generated LV strain, twist, and untwisting rate data. Additionally, beat-by-beat blood pressure was recorded and systemic vascular resistance (SVR) and LV wall stress were calculated. Responses in both exercise trials were statistically similar (P > 0.05). During effort, stroke volume decreased, whereas SVR and LV wall stress increased (P < 0.05). Immediately after effort, stroke volume returned to baseline, whereas SVR and wall stress decreased (P < 0.05). Similarly, acute exercise was accompanied by a significant decrease in systolic parameters of LV muscle mechanics (P < 0.05). However, diastolic parameters, including LV untwisting rate, were statistically unaltered (P > 0.05). Immediately after exercise, systolic LV mechanics returned to baseline levels (P < 0.05) but LV untwisting rate increased significantly (P < 0.05). A single, acute bout of double-leg press resistance exercise transiently reduces systolic LV mechanics, but increases diastolic mechanics after exercise, suggesting that resistance exercise has a differential impact on systolic and diastolic heart muscle function. The findings may explain why acute resistance exercise has been associated with reduced stroke volume but chronic exercise training may result in increased LV volumes.
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Effect of cardiac resynchronization therapy on beat-to-beat T-wave amplitude variability.
Žižek, David; Cvijić, Marta; Tasič, Jerneja; Jan, Matevž; Frljak, Sabina; Zupan, Igor
2012-11-01
T-wave amplitude variability (TAV) is a promising non-invasive predictor of arrhythmic events in patients with dilated cardiomyopathy. We aimed to evaluate the effect of cardiac resynchronization therapy (CRT) on native TAV, its relation with left ventricular (LV) reverse remodelling and the occurrence of ventricular tachyarrhythmias (VTs). In this prospective study, we included 40 heart failure patients with left bundle branch block in sinus rhythm (25 male; 16 with ischaemic aetiology; aged 62.7 ± 9.5 years; New York Heart Association class II-IV). Echocardiographic parameters and TAV were evaluated at baseline and 6 months after implantation of CRT device combined with an implantable cardioverter-defibrillator. T-wave amplitude variability was determined by a 20-min high-resolution electrocardiogram Holter recording during native conduction. After TAV assessment, patients were monitored for 15.7 ± 5.2 months for the occurrence of VTs. Decrease in median TAV [from 40.45 μV (24.75-56.00) to 28.15 μV (20.93-37.95), P = 0.004] was observed after 6 months of CRT. However, decrease of median TAV was only noticed in patients with LV reverse remodelling [46.9 μV (27.5-70.0) to 25.8 μV (20.2-32.4), P < 0.001] and in patients without VTs [40.5 μV (27.5-55.9) to 24.4 μV (17.1-31.5), P < 0.001]. Native median TAV > 35.4 µV after 6 months of CRT had an 83% sensitivity and 93% specificity for predicting the occurrence of VTs. Decrease of TAV after CRT is associated with LV reverse remodelling and indicates a reduction of the intrinsic arrhythmogenic substrate. Median TAV after CRT had a good predicting value for VT occurrence in long-term follow-up.
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Yang, Tao; Wang, Lei; Xiong, Chang-Ming; He, Jian-Guo; Zhang, Yan; Gu, Qing; Zhao, Zhi-Hui; Ni, Xin-Hai; Fang, Wei; Liu, Zhi-Hong
2014-05-01
It is known that patients with pulmonary hypertension (PH) can have elevated F-FDG uptake in the right ventricle (RV) on PET imaging. This study was designed to assess possible relationship between FDG uptake of ventricles and the function/hemodynamics of the RV in patients with PH. Thirty-eight patients with PH underwent FDG PET imaging in both fasting and glucose-loading conditions. The standard uptake value (SUVs) corrected for partial volume effect in both RV and left ventricle (LV) were measured. The ratio of FDG uptake between RV to LV (SUVR/L) was calculated. Right heart catheterization and cardiac magnetic resonance (CMR) were performed in all patients within 1 week. The FDG uptake levels by the ventricles were compared with the result form the right heart catheterization and CMR. The SUV of RV (SUVR) and SUV of LV were significantly higher in glucose-loading condition than in fasting condition. In both fasting and glucose-loading conditions, SUVR and SUVR/L showed reverse correlation with right ventricular ejection fraction derived from CMR. In addition, in both fasting and glucose-loading conditions, SUVR and SUVR/L showed positive correlations with pulmonary vascular resistance. However, only SUVR/L in glucose-loading condition could independently predict right ventricular ejection fraction after adjusted for age, body mass index, sex, mean right atrial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (P = 0.048). The FDG uptake of RV increases with decreased right ventricular function in patients with PH. Increased FDG uptake ratio between RV and LV might be useful to assess the right ventricular function.
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Susic, Dinko; Frohlich, Edward D
2014-05-01
Excessive dietary salt intake induces extensive cardiovascular and renal damage in spontaneously hypertensive rats (SHR) that may be prevented by antihypertensive agents. This study examines whether salt-induced cardiac damage may be reversed by angiotensin II (type 1) receptor blockade (telmisartan). Eight-week-old male SHRs were divided into four groups; Group 1 (NS) was fed regular rat chow, and Group 2 (HS) received high-salt diet (HS; 8% NaCl). After 8 weeks on their respective diets, systemic hemodynamics and indices of left ventricular (LV) function were determined. Group 3 (HSnoT) was given HS for 8 weeks and then switched to a regular chow (0.6% NaCl) diet with no other treatment, and Group 4 (HSArb) received HS for 8 weeks and was then given regular diet plus telmisartan. Rats from these latter two groups were monitored for the ensuing 30 days. Compared with the NS group, rats in the HS group exhibited increased mean arterial pressure (161 ± 7 vs. 184 ± 8 mm Hg) and LV diastolic dysfunction, as evidenced by a decreased rate of LV pressure decline (-8754 ± 747 vs. -4234 ± 754 mmHg/sec) at the end of the 8 weeks of their respective treatment. After switching to regular chow, only one of 11 rats in the HSnoT group survived for the 30 days, whereas 10 died within 18 days; in the HSArb group only one of nine rats died; eight survived 30 days (P < .01). Telmisartan significantly improved LV function and survival in those SHR rats having extensive cardiovascular damage induced by dietary salt excess. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
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Blixt, Martin; Niklasson, Bo; Sandler, Stellan
2007-01-01
Bank voles (Clethrionomys glareolus) kept in captivity develop diabetes mellitus to a significant extent. Also in wild bank voles, elevated blood glucose has been observed. A newly isolated picornavirus named Ljungan virus (LV) has been found in the pancreas of these bank voles. Moreover, LV infection in combination with environmental factors may cause glucose intolerance/diabetes (GINT/D) in normal mice. The aim of the present study was to investigate the functional characteristics of pancreatic islets, isolated from bank voles, bred in the laboratory but considered LV infected. About 20% of all males and females were classified as GINT/D following a glucose tolerance test. Of these animals the majority had become diabetic by 20 weeks of age, with a tendency towards an earlier onset in the males. GINT/D animals had increased serum insulin levels. Islets were tested on the day of isolation (day 0) and after 1 week of culture for their insulin content and their capacity to synthesize (pro)insulin, secrete insulin and metabolize glucose. Functional differences could be observed between normal and GINT/D animals as well as between genders. An elevated basal insulin secretion was observed on day 0 indicating beta-cell dysfunction among islets isolated from diabetic males. In vitro culture could reverse some functional changes. The increased serum insulin level and the increased basal islet insulin secretion may suggest that the animals had developed a type 2 diabetes-like condition. It is likely that the putative stress imposed in the laboratory, maybe in combination with LV infection, can lead to an increased functional demand on the beta-cells.
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Chen, Ting; Zhang, Lv-Ping; Wong, Nai-Kei; Zhong, Ming; Ren, Chun-Hua; Hu, Chao-Qun
2014-03-01
Ovarian maturation in crustaceans is temporally orchestrated by two processes: oogenesis and vitellogenesis. The peptide hormone vitellogenesis-inhibiting hormone (VIH), by far the most potent negative regulator of crustacean reproduction known, critically modulates crustacean ovarian maturation by suppressing vitellogenin (VTG) synthesis. In this study, cDNA encoding VIH was cloned from the eyestalk of Pacific white shrimp, Litopenaeus vannamei, a highly significant commercial culture species. Phylogenetic analysis suggests that L. vannamei VIH (lvVIH) can be classified as a member of the type II crustacean hyperglycemic hormone family. Northern blot and RT-PCR results reveal that both the brain and eyestalk were the major sources for lvVIH mRNA expression. In in vitro experiments on primary culture of shrimp hepatopancreatic cells, it was confirmed that some endogenous inhibitory factors existed in L. vannamei hemolymph, brain, and eyestalk that suppressed hepatopancreatic VTG gene expression. Purified recombinant lvVIH protein was effective in inhibiting VTG mRNA expression in both in vitro primary hepatopancreatic cell culture and in vivo injection experiments. Injection of recombinant VIH could also reverse ovarian growth induced by eyestalk ablation. Furthermore, unilateral eyestalk ablation reduced the mRNA level of lvVIH in the brain but not in the remaining contralateral eyestalk. Our study, as a whole, provides new insights on VIH regulation of shrimp reproduction: 1) the brain and eyestalk are both important sites of VIH expression and therefore possible coregulators of hepatopancreatic VTG mRNA expression and 2) eyestalk ablation could increase hepatopancreatic VTG expression by transcriptionally abolishing eyestalk-derived VIH and diminishing brain-derived VIH.
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Schroeder, Janina; Peterschroeder, Andreas; Vaske, Bernhard; Butz, Thomas; Barth, Peter; Oldenburg, Olaf; Bitter, Thomas; Burchert, Wolfgang; Horstkotte, Dieter; Langer, Christoph
2009-11-01
In humans with normal hearts multi-slice computed tomography (MSCT) based volumetry was shown to correlate well with the gold standard, cardiac magnetic resonance imaging (CMR). We correlated both techniques in patients with various degrees of heart failure and reduced ejection fraction (HFREF) resulting from cardiac dilatation. Twenty-four patients with a left ventricular enddiastolic volume (LV-EDV) of C 150 ml measured by angiography underwent MSCT and CMR scanning for left and right ventricular (LV, RV) volumetry. MSCT based short cardiac axis views were obtained beginning at the cardiac base advancing to the apex. These were reconstructed in 20 different time windows of the RR-interval (0-95%) serving for identification of enddiastole (ED) and end-systole (ES) and for planimetry. ED and ES volumes and the ejection fraction (EF) were calculated for LV and RV. MSCT based volumetry was compared with CMR. MSCT based LV volumetry significantly correlates with CMR as follows: LV-EDV r = 0.94, LV-ESV r = 0.98 and LV-EF r = 0.93, but significantly overestimates LV-EDV and LV-ESV and underestimates EF (P \\ 0.0001). MSCT based RV volumetry significantly correlates with CMR as follows: RV-EDV r = 0.79, RVESV r = 0.78 and RV-EF r = 0.73, but again significantly overestimates RV-EDV and RV-ESV and underestimates RV-EF (P \\ 0.0001). When compared with CMR a continuous overestimation of volumes and underestimation of EF needs to be considered when applying MSCT in HFREF patients.
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Roy, Avijit; Stone, Andrew L; Shao, Jonathan; Otero-Colina, Gabriel; Wei, Gang; Choudhary, Nandlal; Achor, Diann; Levy, Laurene; Nakhla, Mark K; Hartung, John S; Schneider, William L; Brlansky, Ronald H
2015-04-01
Citrus leprosis is one of the most destructive diseases of Citrus spp. and is associated with two unrelated virus groups that produce particles primarily in either the cytoplasm or nucleus of infected plant cells. Symptoms of leprosis, including chlorotic spots surrounded by yellow haloes on leaves and necrotic spots on twigs and fruit, were observed on leprosis-affected mandarin and navel sweet orange trees in the state of Querétaro, Mexico. Serological and molecular assays showed that the cytoplasmic types of Citrus leprosis virus (CiLV-C) often associated with leprosis symptomatic tissues were absent. However, using transmission electron microscopy, bullet-shaped rhabdovirus-like virions were observed in the nuclei and cytoplasm of the citrus leprosis-infected leaf tissues. An analysis of small RNA populations from symptomatic tissue was carried out to determine the genome sequence of the rhabdovirus-like particles observed in the citrus leprosis samples. The complete genome sequence showed that the nuclear type of CiLV (CiLV-N) present in the samples consisted of two negative-sense RNAs: 6,268-nucleotide (nt)-long RNA1 and 5,847-nt-long RNA2, excluding the poly(A) tails. CiLV-N had a genome organization identical to that of Orchid fleck virus (OFV), with the exception of shorter 5' untranslated regions in RNA1 (53 versus 205 nt) and RNA2 (34 versus 182 nt). Phylogenetic trees constructed with the amino acid sequences of the nucleocapsid (N) and glycoproteins (G) and the RNA polymerase (L protein) showed that CiLV-N clusters with OFV. Furthermore, phylogenetic analyses of N protein established CiLV-N as a member of the proposed genus Dichorhavirus. Reverse-transcription polymerase chain reaction primers for the detection of CiLV-N were designed based on the sequence of the N gene and the assay was optimized and tested to detect the presence of CiLV-N in both diseased and symptom-free plants.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Shuyuan; Chen, Jiaxi; Huang, Pintong
Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocationmore » of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation.« less
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Patel, M; Carritt, K; Lane, J; Jayappa, H; Stahl, M; Bourgeois, M
2015-07-01
Four vaccines for feline leukemia virus (FeLV) are available in the United States. This study's purpose was to compare the efficacy of Nobivac feline 2-FeLV (an inactivated, adjuvanted whole-virus vaccine) and PureVax recombinant FeLV (a live, canarypox virus-vectored vaccine) following FeLV challenge. Cats were vaccinated at 9 and 12 weeks with Nobivac feline 2-FeLV (group A, n = 11) or PureVax recombinant FeLV (group B, n = 10). Group C (n = 11) comprised unvaccinated controls. At 3 months postvaccination, cats were immunosuppressed and challenged with FeLV-A/61E. The outcomes measured were persistent antigenemia at 12 weeks postchallenge (PC) and proviral DNA and viral RNA at 3 to 9 weeks PC. Persistent antigenemia was observed in 0 of 11 cats in group A, 5 of 10 cats in group B, and 10 of 11 cats in group C. Group A was significantly protected compared to those in groups B (P < 0.013) and C (P < 0.0001). No difference was found between groups B and C (P > 0.063). The preventable fraction was 100% for group A and 45% for group B. At 9 weeks PC, proviral DNA and viral RNA were detected 1 of 11 cats in group A, 6 of 10 cats in group B, and 9 of 11 cats in group C. Nucleic acid loads were significantly lower in group A than in group C (P < 0.01). Group A had significantly lower proviral DNA loads than group B at weeks 6 to 9 (P < 0.02). The viral RNA loads were significantly lower in group A than in group B at weeks 7 to 9 (P < 0.01). The results demonstrate that Nobivac feline 2-FeLV-vaccinated cats were fully protected against persistent antigenemia and had significantly smaller amounts of proviral DNA and plasma viral RNA loads than PureVax recombinant FeLV-vaccinated cats and unvaccinated controls. Copyright © 2015, Patel et al.
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Gender differences in left ventricular function in patients with isolated aortic stenosis.
Favero, Luca; Giordan, Massimo; Tarantini, Giuseppe; Ramondo, Angelo Bruno; Cardaioli, Paolo; Isabella, Giambattista; Chioin, Raffaello; Lupia, Mario; Razzolini, Renato
2003-05-01
Hypertrophic response of the left ventricle to systolic overload in aortic stenosis appears to be gender-dependent. To examine gender-related differences in left ventricular (LV) function in patients with isolated severe aortic stenosis, 145 patients (65 women, 80 men; mean age 66 +/- 8 years; range: 50 to 89 years) with aortic valve area <0.8 cm2 who underwent cardiac catheterization were studied. No patient had associated myocardial, coronary or other valve disease; patients with diabetes mellitus and systemic hypertension were excluded. No significant differences were seen in aortic valve area between men and women. Neither were there any significant gender-related differences in LV end-systolic and end-diastolic volumes, LV end-diastolic pressure, LV mass indexed by body surface area, LV mass:volume ratio, LV mass:height ratio, elastic stiffness constant, ejection fraction, pulmonary wedge pressure, pulmonary arteriolar resistance and preload. Women showed significantly higher mean transaortic gradient, LV peak systolic pressure and peak systolic stress, end-systolic stress:end-systolic volume ratio, heart rate and cardiac index. In the subgroup of patients with LV pressure >199 mmHg, the mass:volume ratio was increased in men compared with women; of note, the mass:volume ratio in women was not increased in this subgroup compared with the general population. LV pump function in this subgroup was normal and did not differ between men and women. Although no clear-cut difference in hemodynamic parameters was seen, there was a trend towards a less compensatory increase in LV mass in females.
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Helfer-Hungerbuehler, A Katrin; Cattori, Valentino; Boretti, Felicitas S; Ossent, Pete; Grest, Paula; Reinacher, Manfred; Henrich, Manfred; Bauer, Eva; Bauer-Pham, Kim; Niederer, Eva; Holznagel, Edgar; Lutz, Hans; Hofmann-Lehmann, Regina
2010-02-19
In a cat that had ostensibly recovered from feline leukemia virus (FeLV) infection, we observed the reappearance of the virus and the development of fatal lymphoma 8.5 years after the initial experimental exposure to FeLV-A/Glasgow-1. The goals of the present study were to investigate this FeLV reoccurrence and molecularly characterize the progeny viruses. The FeLV reoccurrence was detected by the presence of FeLV antigen and RNA in the blood and saliva. The cat was feline immunodeficiency virus positive and showed CD4+ T-cell depletion, severe leukopenia, anemia and a multicentric monoclonal B-cell lymphoma. FeLV-A, but not -B or -C, was detectable. Sequencing of the envelope gene revealed three FeLV variants that were highly divergent from the virus that was originally inoculated (89-91% identity to FeLV-A/Glasgow-1). In the long terminal repeat 31 point mutations, some previously described in cats with lymphomas, were detected. The FeLV variant tissue provirus and viral RNA loads were significantly higher than the FeLV-A/Glasgow-1 loads. Moreover, the variant loads were significantly higher in lymphoma positive compared to lymphoma negative tissues. An increase in the variant provirus blood load was observed at the time of FeLV reoccurrence. Our results demonstrate that ostensibly recovered FeLV provirus-positive cats may act as a source of infection following FeLV reactivation. The virus variants that had largely replaced the inoculation strain had unusually heavily mutated envelopes. The mutations may have led to increased viral fitness and/or changed the mutagenic characteristics of the virus.
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NASA Astrophysics Data System (ADS)
Gross, Oliver; Sulser, Tullio; Hefermehl, Lukas J.; Strebel, Daniel D.; Largo, Remo; Mortezavi, Ashkan; Poyet, Cédric; Eberli, Daniel; Zimmermann, Matthias; Müller, Alexander; Michel, Maurice S.; Müntener, Michael; Seifert, Hans-Helge; Hermanns, Thomas
2011-03-01
Introduction and objectives: It is unknown if tissue ablation following 120W lithium triborate (LBO) laser vaporization (LV) of the prostate is comparable to that following transurethral resection of the prostate (TURP). Therefore, transrectal 3D-ultrasound volumetry of the prostate was performed to compare the efficiency of tissue ablation between LBO-LV and TURP. Methods: Between 03/2008 and 03/2010 110 patients underwent routine LBO-LV (n=61) or TURP (n=49). Transrectal 3D-ultrasound with planimetric volumetry of the prostate was performed pre-operatively, after catheter removal, 6 weeks and 6 months. Results: Median prostate volume was 52.5ml in the LV group and 46.9ml in the TURP group. After catheter removal, median absolute volume reduction (LV: 7.05ml, TURP: 15.8ml) and relative volume reduction (15.9% vs. 34.2%) were significantly lower in the LV group (p<0.001). After 6 weeks/ 6 months, the relative volume reduction but not the absolute remained significantly lower in the LV group. Conclusions: LBO-LV is an efficient procedure evidenced by an absolute tissue ablation not significantly different to that after TURP. However, TURP seems to be superior due to a higher relative tissue ablation. The differences in tissue ablation had no impact on the early clinical outcome. Delayed volume reduction indicates that prostatic swelling occurs early after LV and then decreases subsequently.
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Meichner, K; Kruse, D B; Hirschberger, J; Hartmann, K
2012-10-06
Progressive infection with feline leukaemia virus (FeLV) is considered one of the major risk factors for development of feline lymphoma. The aim of this study was to compare cats with lymphoma between 1980 and 1994 (first period) and between 1995 and 2009 (second period) concerning FeLV antigenaemia and age distribution. In addition, differences between FeLV antigen-positive and antigen-negative cats with lymphoma regarding patients' characteristics, tumour location and outcome were evaluated. There was a significant decrease in the percentage of lymphoma cases associated with progressive FeLV infection from the first (59 per cent) to the second (13 per cent) observation period. FeLV antigen-positive cats were significantly younger (median 3.7 v 11.3 years), and had significantly shorter response duration (median 25 days v 472 days) with therapy. In the cats of the second period, gastrointestinal and extranodal lymphomas were the most common anatomical sites, and the majority of those cats were FeLV antigen-negative. Thus, other aetiologies than progressive FeLV infection must have a greater impact on cancerogenesis among affected cats with lymphoma to date.
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Hata, Hiroki; Fujita, Tomoyuki; Ishibashi-Ueda, Hatsue; Kuroda, Kensuke; Seguchi, Osamu; Matsumoto, Yorihiko; Yanase, Masanobu; Sato, Takuma; Nakajima, Seiko; Fukushima, Norihide; Kobayashi, Junjiro
2018-06-01
Although mitral regurgitation (MR) is prevalent in patients with end-stage heart failure, the impact of mitral valve (MV) surgery on outcomes after left ventricular assist device (LVAD) implantation and morphologic changes of MV remains unclear. We retrospectively reviewed 74 patients who underwent LVAD implantation as a bridge to transplant. Of these, 11 (15%) underwent MV repair concomitant with or prior to LVAD implantation, while 27 patients with preoperative significant (moderate or greater) MR did not undergo concomitant MV surgery. The mean interval between LVAD implantation and the last echocardiographic examination was 913 days. Irrespective of MV surgery, significant LV reverse remodeling including decreased LV and left atrial dimension and improved MR severity was observed in all patients except for patients with prior MV surgery. Histopathological examination of explanted hearts removed at heart transplantation (n = 69) or autopsy (n = 5) revealed that the MV annulus was still dilated (mean perimeter 11.7 cm) in the patients with preoperative significant MR and no concomitant MV surgery. Concomitant MV surgery at the time of LVAD implantation for significant MR might not be always necessary for bridge to transplant or destination therapy cases. However, it might be required in patients having potential for cardiac recovery or patients with severe pulmonary hypertension and depressed right ventricle.
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Boesch, Andrea; Cattori, Valentino; Riond, Barbara; Willi, Barbara; Meli, Marina L; Rentsch, Katharina M; Hosie, Margaret J; Hofmann-Lehmann, Regina; Lutz, Hans
2015-02-25
Cats persistently infected with the gammaretrovirus feline leukemia virus (FeLV) are at risk to die within months to years from FeLV-associated disease, such as immunosuppression, anemia or lymphoma/leukemia. The integrase inhibitor raltegravir has been demonstrated to reduce FeLV replication in vitro. The aim of the present study was to investigate raltegravir in vivo for its safety and efficacy to suppress FeLV replication. The safety was tested in three naïve specified pathogen-free (SPF) cats during a 15 weeks treatment period (initially 20mg then 40mg orally b.i.d.). No adverse effects were noted. The efficacy was tested in seven persistently FeLV-infected SPF cats attained from 18 cats experimentally exposed to FeLV-A/Glasgow-1. The seven cats were treated during nine weeks (40mg then 80mg b.i.d.). Raltegravir was well tolerated even at the higher dose. A significant decrease in plasma viral RNA loads (∼5×) was found; however, after treatment termination a rebound effect was observed. Only one cat developed anti-FeLV antibodies and viral RNA loads remained decreased after treatment termination. Of note, one of the untreated FeLV-A infected cats developed fatal FeLV-C associated anemia within 5 weeks of FeLV-A infection. Moreover, progressive FeLV infection was associated with significantly lower enFeLV loads prior to infection supporting that FeLV susceptibility may be related to the genetic background of the cat. Overall, our data demonstrate the ability of raltegravir to reduce viral replication also in vivo. However, no complete control of viremia was achieved. Further investigations are needed to find an optimized treatment against FeLV. (250 words). Copyright © 2014 Elsevier B.V. All rights reserved.
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Ruiz-Hurtado, Gema; García-Prieto, Concha F.; Pulido-Olmo, Helena; Velasco-Martín, Juan P.; Villa-Valverde, Palmira; Fernández-Valle, María E.; Boscá, Lisardo; Fernández-Velasco, María; Regadera, Javier; Somoza, Beatriz; Fernández-Alfonso, María S.
2017-01-01
Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30–65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile. PMID:28203206
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Udink ten Cate, Floris EA; Wiesner, Nathalie; Trieschmann, Uwe; Khalil, Markus; Sreeram, Narayanswami
2010-01-01
A subset of children and adults with Wolff-Parkinson-White (WPW) syndrome develop dilated cardiomyopathy (DCM). Although DCM may occur in symptomatic WPW patients with sustained tachyarrhythmias, emerging evidence suggests that significant left ventricular dysfunction may arise in WPW in the absence of incessant tachyarrhythmias. An invariable electrophysiological feature in this non-tachyarrhythmia type of DCM is the presence of a right-sided septal or paraseptal accessory pathway. It is thought that premature ventricular activation over these accessory pathways induces septal wall motion abnormalities and ventricular dyssynchrony. LV dyssynchrony induces cellular and structural ventricular remodelling, which may have detrimental effects on cardiac performance. This review summarizes recent evidence for development of DCM in asymptomatic patients with WPW, discusses its pathogenesis, clinical presentation, management and treatment. The prognosis of accessory pathway-induced DCM is excellent. LV dysfunction reverses following catheter ablation of the accessory pathway, suggesting an association between DCM and ventricular preexcitation. Accessory pathway-induced DCM should be suspected in all patients presenting with heart failure and overt ventricular preexcitation, in whom no cause for their DCM can be found. PMID:20552060
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Single-Center Experience With HeartMate II Left Ventricular Assist Device Explantation.
Tchantchaleishvili, Vakhtang; Cheyne, Christina; Sherazi, Saadia; Melvin, Amber L; Hallinan, William; Chen, Leway; Todd Massey, Howard
2016-12-01
In patients with continuous flow left ventricular assist devices (CF-LVADs) myocardial recovery is uncommon. Given the heterogeneity of the population implanted and low incidence of recovery, the discovery of native left ventricular (LV) recovery and criteria for explantation of CF-LVAD system is not clearly determined. We sought to analyze the characteristics of the patients who underwent CF-LVAD explantation at our institution. Prospectively collected data on patients supported with CF-LVADs were reviewed retrospectively. Patients who underwent CF-LVAD explants were identified and their characteristics were analyzed with a focus on patient presentation and determinants of explantability. From November 2006 to June 2014, 223 patients (181 male, 42 female) underwent implantation of HeartMate II LVAD. Seven female (16.7%) and one male (0.6%) patients were explanted (P < 0.001). Mean age was 43 ± 9 years and etiology for cardiomyopathy was ischemic in three (37.5%) patients, nonischemic in four (50%) patients, and mixed in the one (12.5%) male patient of the cohort. Five (62.5%) patients presented acutely with significant hemolysis, and were found to have LV improvement as well as reduced, absent, or reversed diastolic flow velocities on echocardiography. Overall, mean lactate dehydrogenase level before explantation was 1709 ± 1168 U/L compared to the mean baseline level of 601 ± 316 U/L (P = 0.048). Mean LV ejection fraction (LVEF) improved from 17 ± 7% preimplant to 56 ± 11% pre-explantation (P < 0.001). Median number of days on CF-LVAD support was 870 (interquartile range, 209-975) while mean duration of follow-up after the CF-LVAD explantation was 276 ± 240 days. Mean LVEF dropped from 46 ± 19% postexplantation to 34 ± 10% during the most recent follow-up (P = 0.015). At our institution, patients who underwent LVAD explants were predominantly women with nonischemic cardiomyopathy. Clinical evidence of hemolysis and echocardiographic evidence of reduced or absent diastolic flow velocities were common findings in these patients. Over time, patient's native LV function declined in the absence of LVAD (after LVAD explantation). Significant challenges remain in predicting LV recovery and identifying those individuals who have recovered myocardial function significant enough to be explanted. Copyright © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
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Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender
2009-02-01
Changes in ventricular extracellular matrix (ECM) composition of pressure overload hypertrophy determine clinical outcomes. The effects of mesenchymal stem cell (MSC) transplantation upon determinants of ECM composition in pressure overload hypertrophy have not been studied. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After an absolute decrease in fractional shortening of 25% from baseline, 1 x 10(6) MSC (n = 28) or PBS (n = 20) was randomly injected intracoronarily. LV protein analysis, including matrix metalloproteinases (MMP-2, MMP-3, MMP-6, MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3), was performed after sacrifice on postoperative day 7, 14, 21 or 28. Left ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 were demonstrated to be decreased in the MSC group compared with controls after 28 days. Expression of MMP-2 and TIMP-2 remained relatively stable in both groups. Successful MSCs delivery was confirmed by histological analysis and visualization of labelled MSCs. In this model of pressure overload hypertrophy, intracoronary delivery of MSCs during heart failure was associated with specific changes in determinants of ECM composition. LV reverse remodeling was associated with decreased ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3, which were upregulated in the control group as heart failure progressed. These effects were most significant at 28 days following injection. (c) 2008 John Wiley & Sons, Ltd.
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Marui, Akira; Nishina, Takeshi; Saji, Yoshiaki; Yamazaki, Kazuhiro; Shimamoto, Takeshi; Ikeda, Tadashi; Sakata, Ryuzo
2010-05-01
Surgical ventricular restoration (SVR) has been introduced to restore the dilated left ventricular (LV) chamber and improve LV systolic function; however, SVR has also been reported to detrimentally affect LV diastolic properties. We sought to investigate the impact of preoperative LV diastolic function on outcomes after SVR in patients with heart failure. Sixty-seven patients (60 +/- 14 years) with LV systolic dysfunction (LV ejection fraction, 0.27 +/- 0.10) underwent SVR. They were evaluated by echocardiography preoperatively, and early (
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Armstrong, Craig; Samuel, Jake; Yarlett, Andrew; Cooper, Stephen-Mark; Stembridge, Mike; Stöhr, Eric J.
2016-01-01
Increased left ventricular (LV) twist and untwisting rate (LV twist mechanics) are essential responses of the heart to exercise. However, previously a large variability in LV twist mechanics during exercise has been observed, which complicates the interpretation of results. This study aimed to determine some of the physiological sources of variability in LV twist mechanics during exercise. Sixteen healthy males (age: 22 ± 4 years, V˙O2peak: 45.5 ± 6.9 ml∙kg-1∙min-1, range of individual anaerobic threshold (IAT): 32–69% of V˙O2peak) were assessed at rest and during exercise at: i) the same relative exercise intensity, 40%peak, ii) at 2% above IAT, and, iii) at 40%peak with hypoxia (40%peak+HYP). LV volumes were not significantly different between exercise conditions (P > 0.05). However, the mean margin of error of LV twist was significantly lower (F2,47 = 2.08, P < 0.05) during 40%peak compared with IAT (3.0 vs. 4.1 degrees). Despite the same workload and similar LV volumes, hypoxia increased LV twist and untwisting rate (P < 0.05), but the mean margin of error remained similar to that during 40%peak (3.2 degrees, P > 0.05). Overall, LV twist mechanics were linearly related to rate pressure product. During exercise, the intra-individual variability of LV twist mechanics is smaller at the same relative exercise intensity compared with IAT. However, the absolute magnitude (degrees) of LV twist mechanics appears to be associated with the prevailing rate pressure product. Exercise tests that evaluate LV twist mechanics should be standardised by relative exercise intensity and rate pressure product be taken into account when interpreting results. PMID:27100099
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Armstrong, Craig; Samuel, Jake; Yarlett, Andrew; Cooper, Stephen-Mark; Stembridge, Mike; Stöhr, Eric J
2016-01-01
Increased left ventricular (LV) twist and untwisting rate (LV twist mechanics) are essential responses of the heart to exercise. However, previously a large variability in LV twist mechanics during exercise has been observed, which complicates the interpretation of results. This study aimed to determine some of the physiological sources of variability in LV twist mechanics during exercise. Sixteen healthy males (age: 22 ± 4 years, [Formula: see text]O2peak: 45.5 ± 6.9 ml∙kg-1∙min-1, range of individual anaerobic threshold (IAT): 32-69% of [Formula: see text]O2peak) were assessed at rest and during exercise at: i) the same relative exercise intensity, 40%peak, ii) at 2% above IAT, and, iii) at 40%peak with hypoxia (40%peak+HYP). LV volumes were not significantly different between exercise conditions (P > 0.05). However, the mean margin of error of LV twist was significantly lower (F2,47 = 2.08, P < 0.05) during 40%peak compared with IAT (3.0 vs. 4.1 degrees). Despite the same workload and similar LV volumes, hypoxia increased LV twist and untwisting rate (P < 0.05), but the mean margin of error remained similar to that during 40%peak (3.2 degrees, P > 0.05). Overall, LV twist mechanics were linearly related to rate pressure product. During exercise, the intra-individual variability of LV twist mechanics is smaller at the same relative exercise intensity compared with IAT. However, the absolute magnitude (degrees) of LV twist mechanics appears to be associated with the prevailing rate pressure product. Exercise tests that evaluate LV twist mechanics should be standardised by relative exercise intensity and rate pressure product be taken into account when interpreting results.
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Meyer, Aaron M; Snider, Sarah F; Campbell, Rachael E; Friedman, Rhonda B
2015-10-01
It has been argued that individuals with logopenic variant primary progressive aphasia (lvPPA) have an impairment of the phonological loop, which is a component of the short-term memory (STM) system. In contrast, this type of impairment is not thought to be present in mild typical Alzheimer's disease (AD). Thus, one would predict that people with lvPPA would score significantly lower than a matched AD group on tasks that require phonological STM. In the current study, an lvPPA group was compared with a mild AD group that was matched on age, education, and general cognitive functioning. For a subset of the tasks that involved pseudowords, the AD and lvPPA groups were compared to a healthy control group that was matched on age and education. The lvPPA group was more impaired than the AD group on all of the tasks that required phonological STM, including the pseudoword tasks, but there were no significant differences between these groups on tasks that required visuospatial STM. Compared to the healthy controls, the lvPPA group performed significantly worse on the repetition and reading of pseudowords, while the AD group did not differ significantly from the controls on these tasks. These findings are consistent with the hypothesis that phonological STM is impaired in lvPPA. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Chen, Mei-Pian; Li, Shu-Na; Lam, Wendy W M; Ho, Yuen-Chi; Ha, Shau-Yin; Chan, Godfrey C F; Cheung, Yiu-Fai
2014-04-12
Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin. In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products. Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.
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Guimaraes, Ana M S; Brandão, Paulo E; de Moraes, Wanderlei; Cubas, Zalmir S; Santos, Leonilda C; Villarreal, Laura Y B; Robes, Rogério R; Coelho, Fabiana M; Resende, Mauricio; Santos, Renata C F; Oliveira, Rosangela C; Yamaguti, Mauricio; Marques, Lucas M; Neto, Renata L; Buzinhani, Melissa; Marques, Regina; Messick, Joanne B; Biondo, Alexander W; Timenetsky, Jorge
2009-06-01
A total of 57 captive neotropical felids (one Leopardus geoffroyi, 14 Leopardus pardalis, 17 Leopardus wiedii, 22 Leopardus tigrinus, and three Puma yagouaroundi) from the Itaipu Binacional Wildlife Research Center (Refúgio Bela Vista, Southern Brazil) were anesthetized for blood collection. Feces samples were available for 44 animals, including one L. geoffroyi, eight L. pardalis, 14 L. wiedii, 20 L. tigrinus, and one P. yagouaroundi. Total DNA and RNA were extracted from blood and feces, respectively, using commercial kits. Blood DNA samples were evaluated by polymerase chain reaction (PCR) for feline leukemia virus (FeLV) proviral DNA, whereas reverse transcriptase-PCR was run on fecal samples for detection of coronavirus RNA. None of the samples were positive for coronaviruses. A male L. pardalis and a female L. tigrinus were positive for FeLV proviral DNA, and identities of PCR products were confirmed by sequencing. This is the first evidence of FeLV proviral DNA in these species in Southern Brazil.
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Sims, J A; Giorgi, M C; Oliveira, M A; Meneghetti, J C; Gutierrez, M A
2018-04-01
Extract directional information related to left ventricular (LV) rotation and torsion from a 4D PET motion field using the Discrete Helmholtz Hodge Decomposition (DHHD). Synthetic motion fields were created using superposition of rotational and radial field components and cardiac fields produced using optical flow from a control and patient image. These were decomposed into curl-free (CF) and divergence-free (DF) components using the DHHD. Synthetic radial components were present in the CF field and synthetic rotational components in the DF field, with each retaining its center position, direction of motion and diameter after decomposition. Direction of rotation at apex and base for the control field were in opposite directions during systole, reversing during diastole. The patient DF field had little overall rotation with several small rotators. The decomposition of the LV motion field into directional components could assist quantification of LV torsion, but further processing stages seem necessary. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Navarro, Jose A; Botella, Francisco; Maruhenda, Antonio; Sastre, Pedro; Sánchez-Pina, M Amelia; Pallas, Vicente
2004-05-01
ABSTRACT Nonisotopic molecular dot blot hybridization technique and multiplex reverse transcription-polymerase chain reaction assay for the specific detection of Lettuce big-vein virus (LBVV) and Mirafiori lettuce virus (MiLV) in lettuce tissue were developed. Both procedures were suitable for the specific detection of both viruses in a range of naturally infected lettuce plants from various Spanish production areas and seven different cultivars. The study of the distribution of both viruses in the plant revealed that the highest concentration of LBVV and MiLV occurred in roots and old leaves, respectively. LBVV infection progress in a lettuce production area was faster than that observed for MiLV. In spite of different rates of virus infection progress, most lettuce plants became infected with both viruses about 100 days posttransplant. The appearance of both viruses in lettuce crops was preceded by a peak in the concentration of resting spores and zoosporangia of the fungus vector Olpidium brassicae in lettuce roots.
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Martorana, Eugenio; Pirola, Giacomo Maria; Scialpi, Michele; Micali, Salvatore; Iseppi, Andrea; Bonetti, Luca Reggiani; Kaleci, Shaniko; Torricelli, Pietro; Bianchi, Giampaolo
2017-07-01
To demonstrate the association between magnetic resonance imaging (MRI) estimated lesion volume (LV), prostate cancer detection and tumour clinical significance, evaluating this variable alone and matched with Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. We retrospectively analysed 157 consecutive patients, with at least one prior negative systematic prostatic biopsy, who underwent transperineal prostate MRI/ultrasonography fusion-targeted biopsy between January 2014 and February 2016. Suspicious lesions were delineated using a 'region of interest' and the system calculated prostate volume and LV. Patients were divided in groups considering LV (≤0.5, 0.5-1, ≥1 mL) and PI-RADS score (1-5). We considered clinically significant prostate cancer as all cancers with a Gleason score of ≥3 + 4 as suggested by PI-RADS v2. A direct comparison between MRI estimated LV (MRI LV) and histological tumour volume (HTV) was done in 23 patients who underwent radical prostatectomy during the study period. Differences between MRI LV and HTV were assessed using the paired sample t-test. MRI LV and HTV concordance was verified using a Bland-Altman plot. The chi-squared test and logistic and ordinal regression models were used to evaluate difference in frequencies. The MRI LV and PI-RADS score were associated both with prostate cancer detection (both P < 0.001) and with significant prostate cancer detection (P < 0.001 and P = 0.008, respectively). When the two variables were matched, increasing LV increased the risk within each PI-RADS group. Prostate cancer detection was 1.4-times higher for LVs of 0.5-1 mL and 1.8-times higher for LVs of ≥1 mL; significant prostate cancer detection was 2.6-times for LVs of 0.5-1 mL and 4-times for LVs of ≥1 mL. There was a positive correlation between MRI LV and HTV (r = 0.9876, P < 0.001). Finally, Bland-Altman analysis showed that MRI LV was underestimated by 4.2% compared to HTV. Study limitations include its monocentric and retrospective design and the limited cohort. This study demonstrates that PI-RADS score and the MRI LV, independently and in combination, are associated with prostate cancer detection and with tumour clinical significance. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.
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Pat, Betty; Killingsworth, Cheryl; Chen, Yuanwen; Gladden, James D; Walcott, Greg; Powell, Pamela C; Denney, Thomas; Gupta, Himanshu; Desai, Ravi; Tillson, Michael; Dillon, A Ray; Dell'italia, Louis J
2010-09-01
Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog. MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were obtained at baseline and after 4 months of MR and magnetic resonance imaging (MRI) was performed at sacrifice. MRI-derived, serial, short-axis LV end-diastolic (ED) and end-systolic (ES) volumes, LVED volume/mass ratio, and LV 3-dimensional radius/wall thickness were increased in MR and MR + MCS dogs compared with normal dogs (n = 6) (P < .05). Interstitial collagen was decreased by 30% in both MR and MR + MCS versus normal dogs (P < .05). LV contractility by LV maximum time-varying elastance was significantly depressed in MR and MR + MCS dogs. Furthermore, cardiomyocyte fractional shortening was decreased in MR versus normal dogs and further depressed in MR + MCS dogs (P < .05). In vitro administration of ketotifen to normal cardiomyocytes also significantly decreased fractional shortening and calcium transients. Chronic mast cell stabilization did not attenuate eccentric LV remodeling or collagen loss in MR. However, MCS therapy had a detrimental effect on LV function because of a direct negative inotropic effect on cardiomyocyte function. Published by Elsevier Inc.
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Gleich, Sabine E; Krieger, Stefan; Hartmann, Katrin
2009-12-01
This study was conducted to determine prevalence and risk factors for retrovirus infection of infected cats in a large cat population in Germany by evaluation of 17,462 client-owned cats that were tested for the presence of feline immunodeficiency virus (FIV) antibodies or feline leukaemia virus (FeLV) antigen. The owners of a subset of 100 cats were contacted to determine their cat's survival times. Prevalence of FIV and FeLV was 3.2% and 3.6%, respectively, remaining stable for FIV, but decreasing for FeLV (6-1%) over 10 years. Median age was 6 years in FIV- and 3 years in FeLV-infected cats. Risk factors for FIV infection were male gender, older age, mixed breed, access to outdoor, aggressive behaviour, and FeLV co-infection; and for FeLV infection contact to other cats, aggressive behaviour, and FIV co-infection. Median survival time of FIV-infected cats was not significantly different to non-infected cats, whereas FeLV-infected cats had significantly shorter median survival times than non-infected cats.
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Television, computer and portable display device use by people with central vision impairment
Woods, Russell L; Satgunam, PremNandhini
2011-01-01
Purpose To survey the viewing experience (e.g. hours watched, difficulty) and viewing metrics (e.g. distance viewed, display size) for television (TV), computers and portable visual display devices for normally-sighted (NS) and visually impaired participants. This information may guide visual rehabilitation. Methods Survey was administered either in person or in a telephone interview on 223 participants of whom 104 had low vision (LV, worse than 6/18, age 22 to 90y, 54 males), and 94 were NS (visual acuity 6/9 or better, age 20 to 86y, 50 males). Depending on their situation, NS participants answered up to 38 questions and LV participants answered up to a further 10 questions. Results Many LV participants reported at least “some” difficulty watching TV (71/103), reported at least “often” having difficulty with computer displays (40/76) and extreme difficulty watching videos on handheld devices (11/16). The average daily TV viewing was slightly, but not significantly, higher for the LV participants (3.6h) than the NS (3.0h). Only 18% of LV participants used visual aids (all optical) to watch TV. Most LV participants obtained effective magnification from a reduced viewing distance for both TV and computer display. Younger LV participants also used a larger display when compared to older LV participants to obtain increased magnification. About half of the TV viewing time occurred in the absence of a companion for both the LV and the NS participants. The mean number of TVs at home reported by LV participants (2.2) was slightly but not significantly (p=0.09) higher than NS participants (2.0). LV participants were equally likely to have a computer but were significantly (p=0.004) less likely to access the internet (73/104) compared to NS participants (82/94). Most LV participants expressed an interest in image enhancing technology for TV viewing (67/104) and for computer use (50/74), if they used a computer. Conclusion In this study, both NS and LV participants had comparable video viewing habits. Most LV participants in our sample reported difficulty watching TV, and indicated an interest in assistive technology, such as image enhancement. As our participants reported that at least half their video viewing hours are spent alone and that there is usually more than one TV per household, this suggests that there are opportunities to use image enhancement on the TVs of LV viewers without interfering with the viewing experience of NS viewers. PMID:21410501
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Wei, Xiumei; Liu, Xiangquan; Yang, Jianmin; Fang, Jinghui; Qiao, Hongjin; Zhang, Ying; Yang, Jialong
2012-01-01
C-type lectins play crucial roles in innate immunity to recognize and eliminate pathogens efficiently. In the present study, two C-type lectins from shrimp Litopenaeus vannamei (designated as LvLectin-1 and LvLectin-2) were identified, and their expression patterns, both in tissues and toward pathogen stimulation, were then characterized. The full-length cDNA of LvLectin-1 and LvLectin-2 was 567 and 625 bp, containing an open reading frame (ORF) of 471 and 489 bp, respectively, and deduced amino acid sequences showed high similarity to other members of C-type lectin superfamily. Both two C-type lectins encoded a single carbohydrate-recognition domain (CRD). The motif of Ca(2+) binding site 2 in CRD, which determined carbohydrate-binding specificity, was QPN (Gln(122)-Pro(123)-Asn(124)) in LvLectin-1, but QPD (Gln(128)-Pro(129)-Asp(130)) in LvLectin-2. Two C-type lectins exhibited similar tissue expression pattern, for their mRNA were both constitutively expressed in all tested tissues, including hepatopancreas, muscle, gill, hemocytes, gonad and heart, furthermore they were both mostly expressed in hepatopancreas, though the expression level of LvLectin-2 was much higher than LvLectin-1. The expression level of two C-type lectins mRNA in hemocytes varied greatly after the challenge of Listonella anguillarum or WSSV. After L. anguillarum challenge, the expression of both C-type lectins were significantly (P<0.01) up-regulated compared with blank group, and LvLectin-1 exhibited higher level than LvLectin-2; while after the stimulation of WSSV, the expression of LvLectin-2 was significantly up-regulated at 6 h (P<0.01) and 12 h (P<0.05), but the expression level of LvLectin-1 down-regulated significantly (P<0.01) to 0.4-fold at 6 and 12 h post-stimulation. The results indicated that the two C-type lectins might be involved in immune response toward pathogen infection, and they might perform different recognition specificity toward bacteria or virus. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Li, Ming; Li, Chaozheng; Ma, Chunxia; Li, Haoyang; Zuo, Hongliang; Weng, Shaoping; Chen, Xiaohan; Zeng, Digang; He, Jianguo; Xu, Xiaopeng
2014-10-01
C-type lectins (CTLs) play crucial roles in innate immune responses in invertebrates by recognizing and eliminating microinvaders. In this study, a CTL from pacific white shrimp Litopenaeus vannamei (LvCTL3) was identified. LvCTL3 contains a single C-type lectin-like domain (CTLD), which shows similarities to those of other shrimp CTLs and has a mutated 'EPD' motif in Ca(2+)-binding site 2. LvCTL3 mRNA can be detected in all tested tissues and expression of LvCTL3 in gills was up-regulated after Lipopolysaccharides, poly (I:C), Vibrio parahaemolyticus and white spot syndrome virus (WSSV) challenges, suggesting activation responses of LvCTL3 to bacterial, virus and immune stimulant challenges. The 5'flanking regulatory region of LvCTL3 was cloned and we identified a NF-κB binding motif in the LvCTL3 promoter region. Dual-luciferase reporter assays indicated that over-expression of L. vannamei dorsal can dramatically up regulate the promoter activity of LvCTL3, suggesting that LvCTL3 expression could be regulated through NF-κB signaling pathway. As far as we know, this is the first report on signaling pathway involve in shrimp CTLs expression. The recombinant LvCTL3 protein was expressed in Escherichia coli and purified by Ni-affinity chromatography. The purified LvCTL3 can agglutinate Gram-negative microbe Vibrio alginolyticus and V. parahaemolyticus and Gram-positive bacteria Bacillus subtilis in the presence of calcium ions, but cannot agglutinate Gram-positive bacteria Streptococcus agalactiae. The agglutination activity of LvCTL3 was abolished when Ca(2+) was chelated with EDTA, suggesting the function of LvCTL3 is Ca(2+)-dependent. In vivo challenge experiments showed that the recombinant LvCTL3 protein can significantly reduce the mortalities of V. parahemolyticus and WSSV infection, indicating LvCTL3 might play significant roles in shrimp innate immunity defense against bacterial and viral infection. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Westman, Mark E; Malik, Richard; Hall, Evelyn; Sheehy, Paul A; Norris, Jacqueline M
2017-02-01
Feline leukaemia virus (FeLV) can be a challenging infection to diagnose due to a complex feline host-pathogen relationship and occasionally unreliable test results. This study compared the accuracy of three point-of-care (PoC) FeLV p27 antigen test kits commonly used in Australia and available commercially worldwide (SNAP FIV/FeLV Combo, Witness FeLV/FIV and Anigen Rapid FIV/FeLV), using detection of FeLV provirus by an in-house real-time polymerase chain reaction (qPCR) assay as the diagnostic gold standard. Blood (n=563) and saliva (n=419) specimens were collected from a population of cats determined to include 491 FeLV-uninfected and 72 FeLV-infected individuals (45 progressive infections [p27 and qPCR positive], 27 regressive infections [p27 negative, qPCR positive]). Sensitivity and specificity using whole blood was 63% and 94% for SNAP Combo, 57% and 98% for Witness, and 57% and 98% for Anigen Rapid, respectively. SNAP Combo had a significantly lower specificity using blood compared to the other two kits (P=0.004 compared to Witness, P=0.007 compared to Anigen Rapid). False-positive test results occurred with all three kits using blood, and although using any two kits in parallel increased specificity, no combination of kits completely eliminated the occurrence of false-positive results. We therefore recommend FeLV proviral PCR testing for any cat that tests positive with a PoC FeLV antigen kit, as well as for any cat that has been potentially exposed to FeLV but tests negative with a FeLV antigen kit, before final assignment of FeLV status can be made with confidence. For saliva testing, sensitivity and specificity was 54% and 100%, respectively, for all three test kits. The reduced sensitivity of saliva testing compared to blood testing, although not statistically significant, suggests saliva testing with the current generation of PoC FeLV antigen kits is unsuitable for screening large populations of cats, such as in shelters. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Bolin, Lisa L; Chandhasin, Chandtip; Lobelle-Rich, Patricia A; Albritton, Lorraine M; Levy, Laura S
2011-05-13
Feline leukemia virus (FeLV)-945, a member of the FeLV-A subgroup, was previously isolated from a cohort of naturally infected cats. An unusual multicentric lymphoma of non-T-cell origin was observed in natural and experimental infection with FeLV-945. Previous studies implicated the FeLV-945 surface glycoprotein (SU) as a determinant of disease outcome by an as yet unknown mechanism. The present studies demonstrate that FeLV-945 SU confers distinctive properties of binding to the cell surface receptor. Virions bearing the FeLV-945 Env protein were observed to bind the cell surface receptor with significantly increased efficiency, as was soluble FeLV-945 SU protein, as compared to the corresponding virions or soluble protein from a prototype FeLV-A isolate. SU proteins cloned from other cohort isolates exhibited increased binding efficiency comparable to or greater than FeLV-945 SU. Mutational analysis implicated a domain containing variable region B (VRB) to be the major determinant of increased receptor binding, and identified a single residue, valine 186, to be responsible for the effect. The FeLV-945 SU protein binds its cell surface receptor, feTHTR1, with significantly greater efficiency than does that of prototype FeLV-A (FeLV-A/61E) when present on the surface of virus particles or in soluble form, demonstrating a 2-fold difference in the relative dissociation constant. The results implicate a single residue, valine 186, as the major determinant of increased binding affinity. Computational modeling suggests a molecular mechanism by which residue 186 interacts with the receptor-binding domain through residue glutamine 110 to effect increased binding affinity. Through its increased receptor binding affinity, FeLV-945 SU might function in pathogenesis by increasing the rate of virus entry and spread in vivo, or by facilitating entry into a novel target cell with a low receptor density.
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Bernheim, Alain M; Kiencke, Stephanie; Fischler, Manuel; Dorschner, Lorenz; Debrunner, Johann; Mairbäurl, Heimo; Maggiorini, Marco; Brunner-La Rocca, Hans Peter
2007-08-01
Altitude-induced pulmonary hypertension has been suggested to cause left ventricular (LV) diastolic dysfunction due to ventricular interaction. In this study, we evaluate the effects of exercise- and altitude-induced increase in pulmonary artery pressures on LV diastolic function in an interventional setting investigating high-altitude pulmonary edema (HAPE) prophylaxis. Among 39 subjects, 29 were HAPE susceptible (HAPE-S) and 10 served as control subjects. HAPE-S subjects were randomly assigned to prophylactic tadalafil (10 mg), dexamethasone (8 mg), or placebo bid, starting 1 day before ascent. Doppler echocardiography at rest and during submaximal exercise was performed at low altitude (490 m) and high altitude (4,559 m). The ratio of early transmitral inflow peak velocity (E) to atrial transmitral inflow peak velocity (A), pulmonary venous flow parameters, and tissue velocity within the septal mitral annulus during early diastole (E') were used to assess LV diastolic properties. LV filling pressures were estimated by E/E'. Systolic right ventricular to atrial pressure gradients (RVPGs) were measured in order to estimate pulmonary artery pressures. At 490 m, E/A decreased similarly with exercise in HAPE-S and control subjects (HAPE-S, 1.5 +/- 0.3 to 1.3 +/- 0.3; control, 1.7 +/- 0.4 to 1.3 +/- 0.3; p = 0.12 between groups) [mean +/- SD], whereas RVPG increased significantly more in HAPE-S subjects (20 +/- 5 to 43 +/- 9 mm Hg vs 18 +/- 3 to 28 +/- 3 mm Hg, p < 0.001). Changes in RVPG levels during exercise did not correlate with changes in E/A (p > 0.1). From 490 to 4,559 m, no correlations between changes in RVPG and changes in E/A or atrial reversal (both p > 0.1) were observed. Neither of the groups showed an increase in E/E' from 490 to 4,559 m. Increased pulmonary artery pressure associated with exercise and acute exposure to 4,559 m appears not to cause LV diastolic dysfunction in healthy subjects. Therefore, ventricular interaction seems not to be of hemodynamic relevance in this setting.
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Munro, Hannah J; Berghuis, Lesley; Lang, Andrew S; Rogers, Laura; Whitney, Hugh
2014-04-01
Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses found within domestic and wild cat populations. These viruses cause severe illnesses that eventually lead to death. Housing cats communally for long periods of time makes shelters at high risk for virus transmission among cats. We tested 548 cats from 5 different sites across the island of Newfoundland for FIV and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV, respectively. Two sites had significantly higher seroprevalence of FeLV infection than the other 3 sites. Analysis of sequences from the FeLV env gene (envelope gene) from 6 positive cats showed that 4 fell within the FeLV subtype-A, while 2 sequences were most closely related to FeLV subtype-B and endogenous feline leukemia virus (en FeLV). Varying seroprevalence and the variation in sequences at different sites demonstrate that some shelters are at greater risk of FeLV infections and recombination can occur at sites of high seroprevalence.
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Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E
2017-05-12
Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O 2 , were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10 6 ) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10 6 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were randomized to tail-vein injection of 2×10 6 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume. Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities. © 2017 American Heart Association, Inc.
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Stöhr, Eric J; McDonnell, Barry; Thompson, Jane; Stone, Keeron; Bull, Tom; Houston, Rory; Cockcroft, John; Shave, Rob
2012-01-01
Individuals with high aerobic fitness have lower systolic left ventricular strain, rotation and twist (‘left ventricular (LV) mechanics’) at rest, suggesting a beneficial reduction in LV myofibre stress and more efficient systolic function. However, the mechanisms responsible for this functional adaptation are not known and the influence of aerobic fitness on LV mechanics during dynamic exercise has never been studied. We assessed LV mechanics, LV wall thickness and dimensions, central augmentation index (AIx), aortic pulse wave velocity (aPWV), blood pressure and heart rate in 28 males (age: 21 ± 2 years SD) with a consistent physical activity level (no change >6 months). Individuals were examined at rest and during exercise (40% peak exercise capacity) and separated post hoc into a moderate and high aerobic fitness group (: 49 ± 5 and 63 ± 7 ml kg−1 min−1, respectively, P < 0.0001). At rest and during exercise, there were no significant differences in gross LV structure, AIx, blood pressure or heart rate (P > 0.05). However, for the same AIx, the high group had significantly lower LV apical rotation (P = 0.002) and LV twist (P = 0.003) while basal rotation and strain indices did not differ between groups (P > 0.05). We conclude that young males with high aerobic fitness have lower LV apical rotation at rest and during submaximal exercise that can occur without changes in gross LV structure, arterial haemodynamics or heart rate. The findings suggest a previously unknown type of physiological adaptation of the left ventricle that may have important implications for exercise training in older individuals and patient populations in which exercise training has previously failed to show clear benefits for LV function. PMID:22431336
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Left ventricular dimensions and mass using magnetic resonance imaging in female endurance athletes
NASA Technical Reports Server (NTRS)
Riley-Hagan, M.; Peshock, R. M.; Stray-Gundersen, J.; Katz, J.; Ryschon, T. W.; Mitchell, J. H.
1992-01-01
Few published studies of left ventricular (LV) mass in female endurance athletes have been performed with M-mode echocardiography, which involves assumptions of LV geometry. Therefore, magnetic resonance imaging, a 3-dimensional technique, was used to examine LV mass, LV end-diastolic volume and mean wall thickness in female long distance runners (n = 13; mean age 29 years), cyclists (n = 12; mean age 26 years) and cross-country skiers (n = 11; mean age 24 years), and the findings were compared with sedentary control subjects (n = 10; mean age 27 years) matched for height and body weight. The physical characteristics for all subjects included height (mean 166 cm, and body weight (mean 56 kg). The percent body fat (mean 11.7) and maximal oxygen uptake (VO2max, mean 63 ml.kg-1.min-1) were similar (p greater than 0.05) among all athletic groups, but significantly different from the control group (body fat, mean 22.5%; VO2max, mean 35 ml.kg-1.min-1). LV mass (mean 159 kg), LV end-diastolic volume (mean 122 ml), and mean wall thickness (mean 11.5 mm) were also similar among the athletic groups and significantly larger than the following control values: LV mass (mean 115 g), LV end-diastolic volume (mean 93 ml) and mean wall thickness (mean 9.8 mm). Ratios of LV mass to lean body weight were similar among all athletic groups, although athletic groups had larger ratios (p less than 0.05) than the sedentary control subjects. LV mass/LV end-diastolic volume ratio was similar (p greater than 0.05) among all groups.(ABSTRACT TRUNCATED AT 250 WORDS).
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Pelzer, Uwe; Blanc, Jean-Frédéric; Melisi, Davide; Cubillo, Antonio; Von Hoff, Daniel D; Wang-Gillam, Andrea; Chen, Li-Tzong; Siveke, Jens T; Wan, Yin; Solem, Caitlyn T; Botteman, Marc F; Yang, Yoojung; de Jong, Floris A; Hubner, Richard A
2017-05-09
In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0. Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4-2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9-1.6 months). Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.
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Beutner, S; May, M; Hoschke, B; Helke, C; Lein, M; Roigas, J; Johannsen, M
2007-01-01
This study investigated whether the therapeutic efficacy and morbidity of three minimally invasive techniques for varicocele correction--laparoscopic varicocelectomy (LV), antegrade sclerotherapy (AS), and retrograde embolization (RE)--differed between children and adults. During a 10-year period, 356 procedures for varicocele correction, including 122 cases of LV, 108 cases of AS, and 126 cases of RE, were performed for 314 patients at our institution. Of these patients, 223 were 19 years of age or younger (group 1), and 133 were older than 19 years (group 2). Diagnosis and postoperative results were established clinically and with the use of Doppler ultrasonography. The failure rates and complications for each procedure were retrospectively evaluated and compared between the two age groups. The median follow-up period was 69 months (range, 6-122 months). For 25 patients (19.8%), RE was not feasible for technical reasons. In both groups, LV had a lower failure rate than AS or RE, but the difference between LV and AS was not significant in group 1 (7.7(% vs 11.9%; p > 0.5). Also in group 1, AS was associated with fewer complications than LV 1 (4.5% vs 15.4%; p < 0.05). In group 2, LV was significantly more effective in correcting varicoceles than the other two techniques (p < 0.01). In this group, the complication rates for all three procedures did not differ significantly (p > 0.05). In our experience, LV was more effective than AS or RE in correcting varicoceles. For children and adolescents, AS may be more indicated because of the slightly lower complication rate and similar recurrence rates, as compared with LV, for this age group. The higher incidence of postoperative hydrocele formation after LV warrants more refined techniques such as the lymphatic-sparing approach.
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An Integrin from Shrimp Litopenaeus vannamei Mediated Microbial Agglutination and Cell Proliferation
Zhang, Ying; Wang, Leilei; Wang, Lingling; Wu, Ning; Zhou, Zhi; Song, Linsheng
2012-01-01
Background Integrins are a family of adhesion receptors which regulate cell proliferation, differentiation, leukocyte migration, and complement receptor-dependent phagocytosis. In invertebrates, as a cell adhesion receptor, β integrins play an important role for the balanced activation of immune defense responses especially during the encounter of infections. The present study attempts to characterize the immune functions of shrimp integrin (LvIntegrin) to have better understanding on the immune system and its regulation mechanisms in shrimps. Methodology A shrimp integrin was identified from the Pacific white shrimp Litopenaeus vannamei (designated as LvIntegrin). Its full-length cDNA was of 2621 bp with an open reading frame (ORF) of 2439 bp encoding a polypeptide of 812 amino acids. The mRNA expression of LvIntegrin was significantly up-regulated at 3, 6 and 12 h after Listonella anguillarum challenge. The cDNA fragment encoding β integrin domains (βA and hybrid domain) of LvIntegrin was recombined and expressed in Escherichia coli BL21(DE3)-pLysS. The recombinant protein (rLvIntegrin) could significantly agglutinate the tested microbe including E. coli JM109, L. anguillarum, Micrococcus luteus and Candida dattiladattila in the presence of divalent cations. Moreover, when NIH3T3 cells were cultured with rLvIntegrin, the proliferation rate increased significantly in a dose-dependent manner. Conclusions LvIntegrin, a shrimp β integrin was identified from L. vannamei, shared several highly conserved features. LvIntegrin exhibited broad-spectrum agglutination activity towards both bacteria and fungi and could improve the proliferation of NIH3T3 cells, indicating that LvIntegrin is involved in the immune response against microbe challenge and regulation of cell proliferation as a cell adhesion receptor in shrimp. PMID:22792387
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Zhang, Ying; Wang, Leilei; Wang, Lingling; Wu, Ning; Zhou, Zhi; Song, Linsheng
2012-01-01
Integrins are a family of adhesion receptors which regulate cell proliferation, differentiation, leukocyte migration, and complement receptor-dependent phagocytosis. In invertebrates, as a cell adhesion receptor, β integrins play an important role for the balanced activation of immune defense responses especially during the encounter of infections. The present study attempts to characterize the immune functions of shrimp integrin (LvIntegrin) to have better understanding on the immune system and its regulation mechanisms in shrimps. A shrimp integrin was identified from the Pacific white shrimp Litopenaeus vannamei (designated as LvIntegrin). Its full-length cDNA was of 2621 bp with an open reading frame (ORF) of 2439 bp encoding a polypeptide of 812 amino acids. The mRNA expression of LvIntegrin was significantly up-regulated at 3, 6 and 12 h after Listonella anguillarum challenge. The cDNA fragment encoding β integrin domains (βA and hybrid domain) of LvIntegrin was recombined and expressed in Escherichia coli BL21(DE3)-pLysS. The recombinant protein (rLvIntegrin) could significantly agglutinate the tested microbe including E. coli JM109, L. anguillarum, Micrococcus luteus and Candida dattiladattila in the presence of divalent cations. Moreover, when NIH3T3 cells were cultured with rLvIntegrin, the proliferation rate increased significantly in a dose-dependent manner. LvIntegrin, a shrimp β integrin was identified from L. vannamei, shared several highly conserved features. LvIntegrin exhibited broad-spectrum agglutination activity towards both bacteria and fungi and could improve the proliferation of NIH3T3 cells, indicating that LvIntegrin is involved in the immune response against microbe challenge and regulation of cell proliferation as a cell adhesion receptor in shrimp.
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Aminian, Farimah; Esmaeilzadeh, Maryam; Moladoust, Hassan; Maleki, Majid; Shahrzad, Soraya; Emkanjoo, Zahra; Sadeghpour, Anita
2014-08-01
The aim of this study was to determine the impact of manifest accessory pathway on left ventricle (LV) twist physiology in Wolff-Parkinson-White (WPW) patients. Although this issue was addressed in 1 study based on speckle tracking method, there was no comparative study with a different technique. We planned to use velocity vector imaging (VVI) to find out how much an accessory pathway can affect LV twist mechanics. Thirty patients were enrolled regarding inclusion and exclusion criteria. Two serial comprehensive transthoracic echocardiography evaluations were performed before and after radiofrequency catheter ablation (RFCA) within 24 hours. Stored cine loops were analyzed using VVI technique and LV twist and related parameters were extracted. Comparing pre- and post-RFCA data, no significant changes were observed in LV systolic and diastolic dimensions, LV ejection fraction (LVEF), and Doppler and tissue Doppler-related parameters. VVI study revealed remarkable rise in peak LV apical rotation (10.3º ± 3.0º to 13.8º ± 3.6º, P < 0.001) and basal rotation (-6.0 ± 1.8º to -7.7 ± 1.8º, P < 0.001) after RFCA. Subsequently LV twist showed a surge from 14.7º ± 3.9º to 20.2º ± 4.4º (P < 0.001). LV untwisting rate changed significantly from -96 ± 67 to -149.0 ± 47.5°/sec (P < 0.001) and apical-basal rotation delay showed a remarkable decline after RFCA (106 ± 81 vs. 42.8 ± 26.0 msec, P < 0.001). Accessory pathways have a major impact on LV twist mechanics. © 2013, Wiley Periodicals, Inc.
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Kato, Nobusuke; Kawaguchi, Akira T; Kishida, Akio; Yamaoka, Tetsuji
2013-07-01
Although static cardiomyoplasty prevents the left ventricle (LV) from dilatation, it may interfere with diastolic relaxation, or cause restriction. We developed a synthetic net with dual elasticity and tested its effect late after myocardial infarction in the rat. LV pressure-volume relationships (PVR) were successively analyzed before, after intravenous volume load, and 10 minutes after occlusion of the left anterior descending artery. Rats were then randomized into groups receiving synthetic net wrapping around the heart (NET+, n = 8) and only partially behind LV (NET-, n = 9), and they underwent the same PVR studies 6 weeks later. End-diastolic and end-systolic PVR were defined, and LV size and function were compared under standardized loading conditions. Although there was no difference in Day 0, increase in LV end-diastolic and end-systolic volumes were significantly attenuated in NET+ rats 6 weeks later when there was a significant correlation between LV volumes by PVR estimation and actual measurements, with significant differences in both measures between the groups: NET+ < NET-. The presence or absence of net did not show restrictive hemodynamics under acute volume load. Static cardiomyoplasty using a synthetic elastic net significantly attenuated LV dilatation and dysfunction without restriction late after myocardial infarction in the rat. © 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
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Li, Chaozheng; Chen, Yixiao; Weng, Shaoping; Li, Sedong; Zuo, Hongliang; Yu, Xiaoqiang; Li, Haoyang; He, Jianguo; Xu, Xiaopeng
2014-02-01
The toll-like receptor (TLR)/NF-κB signaling pathways play critical roles in the innate immune system. The intracellular signal transduction of most TLR pathways in invertebrate cells is triggered by formation of a heterotrimeric complex composed of MyD88, Tube and Pelle. In this study, we identified a Litopenaeus vannamei Pelle (LvPelle) and an isoform of L. vannamei Tube (LvTube) designated as LvTube-1. The interactions among LvPelle, LvTube/LvTube-1 and LvMyD88/LvMyD88-1 were elucidated and their functions during pathogen infections were investigated. Knockdowns of LvPelle and LvTube/LvTube-1 using RNAi strategy led to higher mortalities of shrimps during Vibrio parahemolyticus infection, and could reduce the genome copy number of white spot syndrome virus (WSSV) in the infected muscle tissue but did not affect the mortality caused by WSSV infection. The effects of LvPelle and LvTube/LvTube-1 on promoters containing NF-κB binding motifs were analyzed by dual-luciferase reporter assays and the results demonstrated that LvTube-1 could activate the NF-κB activity to significantly higher level than LvTube did. Moreover, tissue distributions of LvTube and LvTube-1 mRNAs and their expression profiles during pathogen and immune stimulant challenges were different, indicating that they could play different roles in immune responses. This is the first report of Tube isoforms in invertebrates. Together with our previous study on LvMyD88 isoforms, our results suggest that various isoforms of adaptor components may be involved in various regulatory patterns of signal transduction in invertebrate TLR/NF-κB pathway and this could be a strategy adopted by invertebrates to modulate immune responses. Copyright © 2013 Elsevier Ltd. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hatakenaka, Masamitsu, E-mail: mhatakenaka@sapmed.ac.jp; Department of Diagnostic Radiology, School of Medicine, Sapporo Medical University, Sapporo; Yonezawa, Masato
2012-05-01
Purpose: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer. Methods and Materials: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parametermore » ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean {+-} SE. Results: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% {+-} 2.98% vs. 59.8% {+-} 2.56% vs. 60.6% {+-} 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 {+-} 2.93 vs. 57.0 {+-} 3.23 mL/m{sup 2}), LV stroke volume index (38.6 {+-} 1.56 vs. 29.9 {+-} 1.60 mL/m{sup 2}), and LV ejection fraction (56.9% {+-} 1.79% vs. 52.8% {+-} 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 {+-} 3.05 vs. 72.4 {+-} 4.04 vs. 85.4 {+-} 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 {+-} 0.54 vs. 4.78 {+-} 0.43 vs. 4.79 {+-} 0.50 mm), 9 (6.88 {+-} 0.45 vs. 5.04 {+-} 0.38 vs. 5.27 {+-} 0.47 mm), and 10 (9.22 {+-} 0.48 vs. 8.08 {+-} 0.34 vs. 8.19 {+-} 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference (p < 0.05) after CCRT between the groups. Conclusions: Concurrent chemoradiotherapy for esophageal cancer impairs LVF from an early treatment stage. This impairment is prominent in patients with high LV dose.« less
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Liang, Gao-Feng; Liang, Yan; Xue, Qinggang; Lu, Jin-Feng; Cheng, Jun-Jun; Huang, Jie
2015-03-01
Cytokines play a critical role in innate and adaptive immunity. Astakines represent a group of invertebrate cytokines that are related to vertebrate prokineticin and function in promoting hematopoiesis in crustaceans. We have identified an astakine from the white shrimp Litopeneaus vannamei and named it LvAST in a previous research. In the present research, we investigated the interactions among LvAST, the envelope protein VP37 of white spot syndrome virus (i.e., WSSV), and the β subunit of F1-ATP synthase (ATPsyn-β) of the white shrimp (i.e., BP53) using binding assays and co-precipitations. We also examined the effects of LvAST on shrimp susceptibility to WSSV. We found that LvAST and VP37 competitively bound to BP53, but did not bind to each other. Shrimps that had been injected with recombinant LvAST exhibited significantly lower mortality and longer survival time in experimental infections by WSSV. In contrast, shrimps whose LvAST gene expression had been inhibited by RNA interference showed significantly higher WSSV infection intensity and shorter survival time following viral challenges. These results suggested that LvAST and WSSV both likely use ATPsyn-β as a receptor and LvAST plays a role in shrimp defense against WSSV infection. This represented the first research showing the involvement of astakines in host antiviral immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Lutale, JJK; Thordarson, H; Gulam-Abbas, Z; Vetvik, K; Gerdts, E
2008-01-01
Summary Background Left ventricular hypertrophy (LV H) has been demonstrated to be a powerful predictor of cardiovascular (CV) morbidity and mortality in diabetic as well as hypertensive patients. However, less is known about the prevalence of electrocardiographic LV H (ECG-LV H) and its relation to other CV risk factors in diabetic patients in sub-Saharan Africa. Therefore, the aim was to assess the prevalence of ECG-LV H in diabetic patients in Dar es Salaam, Tanzania, and its relation to other cardiovascular risk factors. Methods Two hundred and thirty-seven consecutive patients attending the Muhimbili diabetic clinic were studied. ECG-LVH was diagnosed by Sokolow-Lyon voltage and Cornell voltage-duration product criteria. Q waves, ST-segment deviation, T-wave abnormalities and intraventricular conduction defects were classified by the Minnesota codes. Blood pressure (BP), serum creatinine, cholesterol and triglyceride levels, and HbA1c and urinary albumin and creatinine concentrations were determined. Results The prevalence of LV H in patients was 16% by either ECG criteria; 12.2% by Sokolow-Lyon and 5.1% by Cornell product criteria. Patients with LV H had significantly higher systolic and mean BP and pulse pressure, and a higher prevalence of ST-segment abnormalities, T-wave inversion and albuminuria than those without LV H (all p < 0.05). In multivariate logistic regression analysis, systolic BP was the only independent predictor of ECG-LV H. The prevalence of ECG-LV H increased by 15% per 10 mmHg higher systolic BP [OR 1.151 (95% CI 1.00921.314), p < 0.05]. Clustering of cardiovascular risk factors differed significantly between type 1 and type 2 diabetes patients. On average, type 1 patients had 0.8 and type 2 had 2.2 additional CV risk factors. Conclusion ECG-LV H was present in 16% of diabetic patients in Tanzania. Systolic BP was the most important predictor of ECG-LV H. Clustering of CV risks was significantly higher in type 2 than in type 1 diabetics, demonstrating the need for systematic multiple risk-factor assessment in these patients. PMID:18320079
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Dobson, Laura E; Musa, Tarique A; Uddin, Akhlaque; Fairbairn, Timothy A; Bebb, Owen J; Swoboda, Peter P; Haaf, Philip; Foley, James; Garg, Pankaj; Fent, Graham J; Malkin, Christopher J; Blackman, Daniel J; Plein, Sven; Greenwood, John P
2017-02-22
Left bundle branch block (LBBB) is common following trans-catheter aortic valve replacement (TAVR) and has been linked to increased mortality, although whether this is related to less favourable cardiac reverse remodeling is unclear. The aim of the study was to investigate the impact of TAVR induced LBBB on cardiac reverse remodeling. 48 patients undergoing TAVR for severe aortic stenosis were evaluated. 24 patients with new LBBB (LBBB-T) following TAVR were matched with 24 patients with a narrow post-procedure QRS (nQRS). Patients underwent cardiovascular magnetic resonance (CMR) prior to and 6 m post-TAVR. Measured cardiac reverse remodeling parameters included left ventricular (LV) size, ejection fraction (LVEF) and global longitudinal strain (GLS). Inter- and intra-ventricular dyssynchrony were determined using time to peak radial strain derived from CMR Feature Tracking. In the LBBB-T group there was an increase in QRS duration from 96 ± 14 to 151 ± 12 ms (P < 0.001) leading to inter- and intra-ventricular dyssynchrony (inter: LBBB-T 130 ± 73 vs nQRS 23 ± 86 ms, p < 0.001; intra: LBBB-T 118 ± 103 vs. nQRS 13 ± 106 ms, p = 0.001). Change in indexed LV end-systolic volume (LVESVi), LVEF and GLS was significantly different between the two groups (LVESVi: nQRS -7.9 ± 14.0 vs. LBBB-T -0.6 ± 10.2 ml/m 2 , p = 0.02, LVEF: nQRS +4.6 ± 7.8 vs LBBB-T -2.1 ± 6.9%, p = 0.002; GLS: nQRS -2.1 ± 3.6 vs. LBBB-T +0.2 ± 3.2%, p = 0.024). There was a significant correlation between change in QRS and change in LVEF (r = -0.434, p = 0.002) and between change in QRS and change in GLS (r = 0.462, p = 0.001). Post-procedure QRS duration was an independent predictor of change in LVEF and GLS at 6 months. TAVR-induced LBBB is associated with less favourable cardiac reverse remodeling at medium term follow up. In view of this, every effort should be made to prevent TAVR-induced LBBB, especially as TAVR is now being extended to a younger, lower risk population.
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Zhang, Huijie; Zhang, Tao; Li, Shengxu; Guo, Yajun; Shen, Wei; Fernandez, Camilo; Harville, Emily; Bazzano, Lydia A; Urbina, Elaine M; He, Jiang; Chen, Wei
2017-05-12
Childhood adiposity is associated with cardiac structure in later life, but little is known regarding to what extent childhood body weight affects adult left ventricular geometric patterns through adult body size and blood pressure (BP). Determine quantitatively the mediation effect of adult body weight and BP on the association of childhood body mass index (BMI) with adult left ventricular (LV) hypertrophy. This longitudinal study consisted of 710 adults, aged 26 to 48 years, who had been examined for BMI and BP measured ≥4× during childhood and ≥2× during adulthood, with a mean follow-up period of 28.0 years. After adjusting for age, race, and sex, adult BMI had a significant mediation effect (76.4%; P <0.01) on the childhood BMI-adult LV mass index association. The mediation effects of adult systolic BP (15.2%), long-term burden (12.1%), and increasing trends of systolic BP (7.9%) were all significant ( P <0.01). Furthermore, these mediators also had significant mediation effects on the association of childhood BMI with adult LV hypertrophy, eccentric hypertrophy, and concentric hypertrophy. Importantly, the mediation effects of adult BMI were all significantly stronger than those of adult systolic BP on LV mass index, LV hypertrophy, and LV remodeling patterns ( P <0.01). Additionally, the mediation effect of systolic BP on concentric hypertrophy was significantly stronger than that on eccentric hypertrophy ( P <0.01). These findings suggest that increased childhood BMI has long-term adverse impact on subclinical changes in adult cardiac structure, and early life excessive body weight and adult LV hypertrophy are linked through later life excessive body weight and elevated BP. © 2017 American Heart Association, Inc.
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Di Marco, Giovana Seno; Reuter, Stefan; Kentrup, Dominik; Grabner, Alexander; Amaral, Ansel Philip; Fobker, Manfred; Stypmann, Jörg; Pavenstädt, Hermann; Wolf, Myles; Faul, Christian; Brand, Marcus
2014-01-01
Background Activation of fibroblast growth factor receptor (FGFR)-dependent signalling by FGF23 may contribute to the complex pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease (CKD). Pan FGFR blockade by PD173074 prevented development of LVH in the 5/6 nephrectomy rat model of CKD, but its ability to treat and reverse established LVH is unknown. Methods CKD was induced in rats by 5/6 nephrectomy. Two weeks later, rats began treatment with vehicle (0.9% NaCl) or PD173074, 1 mg/kg once-daily for 3 weeks. Renal function was determined by urine and blood analyses. Left ventricular (LV) structure and function were determined by echocardiography, histopathology, staining for myocardial fibrosis (Sirius-Red) and investigating cardiac gene expression profiles by real-time PCR. Results Two weeks after inducing CKD by 5/6 nephrectomy, rats manifested higher (mean ± SEM) systolic blood pressure (208 ± 4 versus 139 ± 3 mmHg; P < 0.01), serum FGF23 levels (1023 ± 225 versus 199 ± 9 pg/mL; P < 0.01) and LV mass (292 ± 9 versus 220 ± 3 mg; P < 0.01) when compared with sham-operated animals. Thereafter, 3 weeks of treatment with PD173074 compared with vehicle did not significantly change blood pressure, kidney function or metabolic parameters, but significantly reduced LV mass (230 ± 14 versus 341 ± 33 mg; P < 0.01), myocardial fibrosis (2.5 ± 0.7 versus 5.4 ± 0.95% staining/field; P < 0.01) and cardiac expression of genes associated with pathological LVH, while significantly increasing ejection fraction (18 versus 2.5% post-treatment increase; P < 0.05). Conclusions FGFR blockade improved cardiac structure and function in 5/6 nephrectomy rats with previously established LVH. These data support FGFR activation as a potentially modifiable, blood pressure-independent molecular mechanism of LVH in CKD. PMID:24875663
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Smith, Danielle N; Bonagura, John D; Culwell, Nicole M; Schober, Karsten E
2012-03-01
The presence of left ventricular (LV) systolic dysfunction may influence prognosis or therapy in dogs with chronic mitral regurgitation (MR). Assessment of LV function in MR by conventional echocardiography is confounded by altered ventricular loading. Myocardial deformation (strain) imaging might offer more sensitive estimates of LV function in this disease. Prospectively measure myocardial strain in dogs with asymptomatic MR compared to a control group. Forty healthy dogs (3.5-11.5 kg): 20 Controls; 20 dogs with MR and LV remodeling (Stage B2), were evaluated in this study. LV size and function were assessed in a short-axis plane. Segmental radial strain and strain rate and global circumferential strain were measured using a 2D echocardiographic speckle-tracking algorithm (GE EchoPAC). Groups were compared using Bonferroni t-tests. Influences of heart rate and body weight were explored with linear regression. The MR group had significantly greater mean values for heart rate, LV size, and LV systolic function. Specifically, LV diastolic diameter, diastole area, shortening fraction, averaged peak systolic and early diastolic radial strain, global circumferential strain, and averaged radial strain rate were significantly greater in the MR group (p < 0.015 to p < 0.001). Strain was unrelated to weight, but weakly correlated with heart rate. Similar to conventional indices, Stage B2 dogs with MR demonstrate hyperdynamic deformation in the short-axis plane. Short-axis strain variables measured by 2D speckle tracking are greater than for controls of similar age and weight. These results imply either preserved LV systolic function or that LV dysfunction is masked by altered ventricular loading. Copyright © 2012 Elsevier B.V. All rights reserved.
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Cao, Yuan-Yuan; Su, Yan-Gang; Bai, Jin; Wang, Wei; Wang, Jing-Feng; Qin, Sheng-Mei; Ge, Jun-Bo
2015-01-01
Loss of left ventricular (LV) capture may lead to deterioration of heart failure in patients with cardiac resynchronization therapy (CRT). Recognition of loss of LV capture in time is important in clinical practice. A total of 422 electrocardiograms were acquired and analyzed from 53 CRT patients at 8 different pacing settings (LV only, right ventricle [RV] only, biventricular [BV] pacing with LV preactivation of 60, 40, 20, and 0 milliseconds and RV preactivation of 20 and 40 milliseconds). A modified Ammann algorithm by adding a third step-presence of Q (q, or QS) wave-to the original 2-step Ammann algorithm and a QRS axis shift method were devised to identify the loss of LV capture. The accuracy of modified Ammann algorithm was significantly higher than that of Ammann algorithm (78.9% vs. 69.1%, P < 0.001). The accuracy of the axis shift method was 66.4%, which was significantly lower than the modified Ammann algorithm (P < 0.001) and similar to the original one (P = 0.412). However, in the ECGs with QRS axis shift, 96.8% were correctly classified. LV preactivation or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall could elevate the accuracies of the modified Ammann algorithm and the QRS axis shift method. The accuracy of the modified Ammann algorithm is greatly improved. The QRS axis shift method can help diagnose LV capture. The LV preactivation, or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall can increase the diagnostic power of the modified Ammann algorithm and QRS axis shift method. © 2014 Wiley Periodicals, Inc.
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Palit, Arnab; Bhudia, Sunil K; Arvanitis, Theodoros N; Turley, Glen A; Williams, Mark A
2015-02-26
Majority of heart failure patients who suffer from diastolic dysfunction retain normal systolic pump action. The dysfunction remodels the myocardial fibre structure of left-ventricle (LV), changing its regular diastolic behaviour. Existing LV diastolic models ignored the effects of right-ventricular (RV) deformation, resulting in inaccurate strain analysis of LV wall during diastole. This paper, for the first time, proposes a numerical approach to investigate the effect of fibre-angle distribution and RV deformation on LV diastolic mechanics. A finite element modelling of LV passive inflation was carried out, using structure-based orthotropic constitutive law. Rule-based fibre architecture was assigned on a bi-ventricular (BV) geometry constructed from non-invasive imaging of human heart. The effect of RV deformation on LV diastolic mechanics was investigated by comparing the results predicted by BV and single LV model constructed from the same image data. Results indicated an important influence of RV deformation which led to additional LV passive inflation and increase of average fibre and sheet stress-strain in LV wall during diastole. Sensitivity of LV passive mechanics to the changes in the fibre distribution was also examined. The study revealed that LV diastolic volume increased when fibres were aligned more towards LV longitudinal axis. Changes in fibre angle distribution significantly altered fibre stress-strain distribution of LV wall. The simulation results strongly suggest that patient-specific fibre structure and RV deformation play very important roles in LV diastolic mechanics and should be accounted for in computational modelling for improved understanding of the LV mechanics under normal and pathological conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Henderson, L E; Sowder, R; Copeland, T D; Smythers, G; Oroszlan, S
1984-01-01
The structural proteins of murine type C retroviruses are proteolytic cleavage products of two different precursor polyproteins coded by the viral gag and env genes. To further investigate the nature and number of proteolytic cleavages involved in virus maturation, we quantitatively isolated the structural proteins of the Rauscher and Moloney strains of type C murine leukemia virus (R-MuLV and M-MuLV, respectively) by reversed-phase high-pressure liquid chromatography. Proteins and polypeptides isolated from R-MuLV included p10, p12, p15, p30, p15(E), gp69, and gp71 and three previously undescribed virus components designated here as p10', p2(E), and p2(E). Homologous proteins and polypeptides were isolated from M-MuLV. Complete or partial amino acid sequences of all the proteins listed above were either determined in this study or were available in previous reports from this laboratory. These data were compared with those from the translation of the M-MuLV proviral DNA sequence (Shinnick et al., Nature [London] 293:543-548, 1981) to determine the exact nature of proteolytic cleavages for all the structural proteins described above and to determine the origin of p10' and p2(E)s. The results showed that, during proteolytic processing of gp80env from M-MuLV (M-gp 80env), a single Arg residue was excised between gp70 and p15(E) and a single peptide bond was cleaved between p15(E) and p2(E). The structure of M-gPr80env is gp70-(Arg)-p15(E)-p2(E). The data suggest that proteolytic cleavage sites in R-gp85env are identical to corresponding cleavage sites in M-gp80env. The p2(E)s are shown to be different genetic variants of p2(E) present in the uncloned-virus preparations. The data for R- and M-p10's shows that they are cleavage products of the gag precursor with the structure p10-Thr-Leu-Asp-Asp-OH. The complete structure of Pr65gag is p15-p12-p30-p10'. Stoichiometries of the gag and env cleavage products in mature R- and M-MuLV were determined. In each virus, gag cleavage products (p15, p12, p30, and p10 plus p10') were found in equimolar amounts and p15(E)s were equimolar with p2(E)s. The stoichiometry of gag to env cleavage products was 4:1. These data are consistent with the proposal that proteolytic processing of precursor polyproteins occurs after virus assembly and that the C-terminal portion of Pr15(E) [i.e., p15(E)-p2(E)] is located on the inner side of the lipid bilayer of the virus. Images PMID:6333515
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Kang, Soo Jung; Cho, Young Sun; Hwang, Seo Jung; Kim, Hyo Jin
2017-12-01
To evaluate the outcomes of left ventricular (LV) function according to treatment response for a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Echocardiograms of 21 preterm infants born at gestational age < 31 weeks obtained at term-equivalent age were retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation after failure of pharmacological closure (ligation group) and 6 experienced successful pharmacological closure (medication group). Six preterm infants without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal systolic strain (ε) of each infant was retrospectively obtained from echocardiograms using velocity vector imaging, along with neonatal outcomes. Pharmacological closures were attempted at postnatal day 2-3. In the ligation group, the median postnatal age at ligation was 20 days. In the ligation group, LV peak longitudinal systolic ε was significantly decreased at term-equivalent age compared to the other groups. Between the medication and no-hsPDA groups, LV peak longitudinal systolic ε did not differ significantly. Among the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC) showed significantly decreased LV peak longitudinal systolic ε compared to the infants who did not experience NEC . We speculate that in preterm infants with an hsPDA, in cases of medical treatment failure, early PDA ligation at less than 20 days of postnatal age would be beneficial for preserving LV systolic function.
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Zreik, Majd; Lessmann, Nikolas; van Hamersvelt, Robbert W; Wolterink, Jelmer M; Voskuil, Michiel; Viergever, Max A; Leiner, Tim; Išgum, Ivana
2018-02-01
In patients with coronary artery stenoses of intermediate severity, the functional significance needs to be determined. Fractional flow reserve (FFR) measurement, performed during invasive coronary angiography (ICA), is most often used in clinical practice. To reduce the number of ICA procedures, we present a method for automatic identification of patients with functionally significant coronary artery stenoses, employing deep learning analysis of the left ventricle (LV) myocardium in rest coronary CT angiography (CCTA). The study includes consecutively acquired CCTA scans of 166 patients who underwent invasive FFR measurements. To identify patients with a functionally significant coronary artery stenosis, analysis is performed in several stages. First, the LV myocardium is segmented using a multiscale convolutional neural network (CNN). To characterize the segmented LV myocardium, it is subsequently encoded using unsupervised convolutional autoencoder (CAE). As ischemic changes are expected to appear locally, the LV myocardium is divided into a number of spatially connected clusters, and statistics of the encodings are computed as features. Thereafter, patients are classified according to the presence of functionally significant stenosis using an SVM classifier based on the extracted features. Quantitative evaluation of LV myocardium segmentation in 20 images resulted in an average Dice coefficient of 0.91 and an average mean absolute distance between the segmented and reference LV boundaries of 0.7 mm. Twenty CCTA images were used to train the LV myocardium encoder. Classification of patients was evaluated in the remaining 126 CCTA scans in 50 10-fold cross-validation experiments and resulted in an area under the receiver operating characteristic curve of 0.74 ± 0.02. At sensitivity levels 0.60, 0.70 and 0.80, the corresponding specificity was 0.77, 0.71 and 0.59, respectively. The results demonstrate that automatic analysis of the LV myocardium in a single CCTA scan acquired at rest, without assessment of the anatomy of the coronary arteries, can be used to identify patients with functionally significant coronary artery stenosis. This might reduce the number of patients undergoing unnecessary invasive FFR measurements. Copyright © 2017 Elsevier B.V. All rights reserved.
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Left ventricular rotation and torsion in patients with perimembranous ventricular septal defect.
Zhuang, Yan; Yong, Yong-hong; Yao, Jing; Ji, Ling; Xu, Di
2014-03-01
Assessment of left ventricular (LV) rotation has become an important approach for quantifying LV function. In this study, we sought to analyze LV rotation and twist using speckle tracking imaging (STI) in adult patients with isolated ventricular septal defects. Using STI, the peak rotation and time to peak rotation of 6 segments in basal and apical short-axis were measured, respectively, in 32 patients with ventricular septal defect and 30 healthy subjects as controls. The global rotation of the 6 segments in basal and apical and LV twist versus time profile were drawn, the peak rotation and twist of LV were calculated. All the time to peak rotation/twist were expressed as a percentage of end-systole (end-systole = 100%). Left ventricular ejection fraction was measured by biplane Simpson method. In patients group, the peak rotation of posterior, inferior, and postsept wall in basal was higher(P ≤ 0.05) and LV twist was also higher (P ≤ 0.05) than healthy controls. There were no significant differences between 2 groups in the peak rotation of the other 9 segments and left ventricular ejection fraction. Different from the control group, the time to peak rotation of the 6 segments in basal were delayed and the global rotation of the base was delayed (P ≤ 0.05) in ventricular septal defect group. Left ventricular volume overload due to ventricular septal defect has significant effect on LV rotation and twist, and LV rotation and twist may be a new index predicting LV systolic function. © 2013, Wiley Periodicals, Inc.
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Yang, Linwei; Niu, Shengwen; Gao, Jiefeng; Zuo, Hongliang; Yuan, Jia; Weng, Shaoping; He, Jianguo; Xu, Xiaopeng
2018-02-01
The single whey acidic protein (WAP) domain (SWD)-containing proteins, also called type III crustins, are a group of antimicrobial peptides (AMPs) in crustaceans. At present, a number of SWDs have been identified in shrimp, which showed essential antibacterial activities. However, the roles of SWDs in antiviral immune responses have not been reported up to now. In this study, a novel SWD (LvSWD3) was identified from Pacific white shrimp, Litopenaeus vannamei, which contained a typical single WAP domain homologous to those of other crustacean SWDs. Although lacking the pro and arg-rich region between the signal peptide and the WAP domain, LvSWD3 was closely clustered with other shrimp SWDs in the phylogenetic tree. Similar to many shrimp SWDs, the highest expression of LvSWD3 was detected in hemocytes. The LvSWD3 expression exhibited only limited changes after challenges with Vibrio parahaemolyticus, Poly (I:C) and lipopolysaccharide, but was significantly up-regulated after white spot syndrome virus (WSSV) infection. Silencing of LvSWDs significantly accelerated the death of the WSSV-infected but not the V. parahaemolyticus-infected shrimp. The recombinant LvSWD3 protein did not show proteinase inhibitory and antibacterial activities but could significantly postpone the death of WSSV-infected shrimp and reduce the viral load in tissues. These suggested that LvSWD3 was a novel SWD with antiviral activity. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Hamabe, L; Kim, S; Yoshiyuki, R; Fukayama, T; Nakata, T M; Fukushima, R; Tanaka, R
2015-01-01
Closure of PDA can be associated with echocardiographic changes including deterioration of LV systolic function. Although PDA is commonly encountered in dogs, few comprehensive reports of echocardiographic changes in dogs with PDA closure are available. To evaluate the short-term echocardiographic changes observed after PDA closure in dogs using strain analysis. Seventeen client-owned dogs with left-to-right PDA. Echocardiographic evaluations, including standard echocardiography and two-dimensional tissue tracking (2DTT), were performed before and within 3 days of PDA closure. Preclosure examination showed LV and left atrial dilatation indicating volume overload as a result of PDA. Closure of PDA resulted in significant reduction of LVIDd (<.0001) and LA/Ao (0.01) without change in LVIDs, suggestive of decreased preload. Postclosure LV systolic dysfunction was observed with significant decreased in FS (<.0001) and strain values (P = .0039 for radial strains, P = .0005 for circumferential strains). Additionally, significant LV dyssynchrony (P = .0162) was observed after closure of PDA. Closure of PDA resulted in decreased preload as a result of alleviation of LV volume overload, which in turn caused transient deterioration of LV systolic function. Additionally, this study demonstrated that strain analysis is load dependent. Therefore, care should be taken when interpreting strain measurements as an indicator of LV systolic function. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.
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Chantler, Paul D; Nussbacher, Amit; Gerstenblith, Gary; Schulman, Steven P; Becker, Lewis C; Ferrucci, Luigi; Fleg, Jerome L; Lakatta, Edward G; Najjar, Samer S
2011-05-01
The coupling between arterial elastance (E(A); net afterload) and left ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, E(A) was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV) did not differ between old (70 ± 8 yr, n = 15) and young (30 ± 5 yr, n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 ± 3.1 mmHg/ml) versus young (11.4 ± 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 ± 0.11) versus young (0.16 ± 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction in E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.
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Lord, Rachel; MacLeod, David; George, Keith; Oxborough, David; Shave, Rob; Stembridge, Mike
2018-04-01
What is the central question of this study? A reduction in left ventricular (LV) filling, and concomitant increase in heart rate, augments LV mechanics to maintain stroke volume (SV); however, the impact of reduced LV filling in isolation on SV and LV mechanics is currently unknown. What is the main finding and its importance? An isolated decrease in LV filling did not provoke a compensatory increase in mechanics to maintain SV; in contrast, LV mechanics and SV were reduced. These data indicate that when LV filling is reduced without changes in heart rate, LV mechanics do not compensate to maintain SV. An acute non-invasive reduction in preload has been shown to augment cardiac mechanics to maintain stroke volume and cardiac output. Such interventions induce concomitant changes in heart rate, whereas blood volume extraction reduces preload without changes in heart rate. Therefore, the purpose of this study was to determine whether a preload reduction in isolation resulted in augmented stroke volume achieved via enhanced cardiac mechanics. Nine healthy volunteers (four female, age 29 ± 11 years) underwent echocardiography for the assessment of left ventricular (LV) volumes and mechanics in a supine position at baseline and end extraction after the controlled removal of 25% of total blood volume (1062 ± 342 ml). Arterial blood pressure was monitored continuously by a pressure transducer attached to an indwelling radial artery catheter. Heart rate and total peripheral resistance were unchanged from baseline to end extraction, but systolic blood pressure was reduced (from 148 to 127 mmHg). From baseline to end extraction there were significant reductions in left ventricular end-diastolic volume (from 89 to 71 ml) and stroke volume (from 56 to 37 ml); however, there was no change in LV twist, basal or apical rotation. In contrast, LV longitudinal strain (from -20 to -17%) and basal circumferential strain (from -22 to -19%) were significantly reduced from baseline to end extraction. In conclusion, a reduction in preload during blood volume extraction does not result in compensatory changes in stroke volume or cardiac mechanics. Our data suggest that LV strain is dependent on LV filling and consequent geometry, whereas LV twist could be mediated by heart rate. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.
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Follistatin-like 1 in Chronic Systolic Heart Failure: A Marker of Left Ventricular Remodeling
El-Armouche, Ali; Ouchi, Noriyuki; Tanaka, Komei; Doros, Gheorghe; Wittköpper, Katrin; Schulze, Thomas; Eschenhagen, Thomas; Walsh, Kenneth; Sam, Flora
2011-01-01
Background Follistatin-like 1 (FSTL1) is an extracellular glycoprotein that is found in human serum. Recent work suggests that FSTL1 is secreted in response to ischemic injuries and that its overexpression is protective in the heart and vasculature. Methods and Results Here, we examined serum FSTL1 levels in patients with chronic heart failure with left ventricular (LV) ejection fraction <40% (n=86). The distribution of the sample, from these chronic heart failure patients, was separated into three tertiles of low, medium and high FSTL1 levels. Serum FSTL1 levels were increased 56% above age- and gender-matched, healthy controls. Diabetes mellitus, brain natriuretic peptide level, left atrial size, LV posterior wall thickness, LV end-diastolic diameter and LV mass were significant determinants of FSTL1 serum levels by bivariate analysis. After controlling for significant covariates, FSTL1 levels predicted LV hypertrophy (as measured by LV mass index) by multivariate linear regression analysis (P<0.001). Unadjusted survival analysis demonstrated increased mortality in patients with increasing FSTL1 levels (P=0.09). After adjusting for significant parameters, patients with increased FSTL1 remained at the highest risk of death [hazard ratio (95% confidence limits) 1.028, (0.98 and 1.78)]; (P=0.26). To determine whether elevated FSTL1 may be derived from the myocardium, FSTL1 protein expression was measured in samples from explanted, failing (n=18) and non-failing human hearts (n=7). LV failing hearts showed 2.5-fold higher FSTL1 protein levels than non-failing control hearts (P<0.05). Conclusions Elevated serum FSTL1 in human heart failure patients was associated with LV hypertrophy. Further studies on the role of FSTL1 as a biomarker in chronic systolic heart failure are warranted. PMID:21622850
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Nagase, Hideki; Nakagawa, Fumio; Uchida, Junji
2018-01-01
A phase 3 trial of S-1, leucovorin (LV), and oxaliplatin for treating gastric cancer is now underway. However, the antitumor efficacy of the combination has not yet been examined in an in vivo preclinical study. This study examined the antitumor efficacy of combination therapy consisting of S-1, LV, and oxaliplatin against 4 human gastric cancer xenografts: NUGC-4, St-40, SC-2, and SC-4. The antitumor efficacy was evaluated using human gastric cancer xenograft-bearing nude mice. S-1 and LV were administered orally once daily on days 1-7 at doses of 6.9 and 10 mg/kg, respectively. Oxaliplatin was administered intravenously at a dose of 8.3 mg/kg on day 1. The tumor volume was measured on day 15, and the relative tumor volume (RTV) was calculated. In all 4 xenograft models, S-1 alone and oxaliplatin alone, but not LV alone, had significant antitumor activities (p < 0.001). Combination therapy consisting of S-1 and LV resulted in a significantly smaller RTV than S-1 alone (p < 0.001). Combination therapy consisting of S-1 and oxaliplatin also resulted in a significantly smaller RTV than either S-1 alone (p < 0.001) or oxaliplatin alone (p < 0.001). Furthermore, combination therapy consisting of S-1, LV, and oxaliplatin resulted in the highest antitumor activity in these models (p < 0.001 vs. S-1 + LV; p < 0.001 or p = 0.003 vs. S-1 + oxaliplatin). Combination therapy consisting of S-1, LV, and oxaliplatin administered according to a 1-week-on/1-week-off schedule may be useful for the treatment of patients with gastric cancer. © 2018 S. Karger AG, Basel.
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Altered LV inotropic reserve and mechanoenergetics early in the development of heart failure.
Prabhu, S D; Freeman, G L
2000-03-01
To test the hypothesis that alterations in left ventricular (LV) mechanoenergetics and the LV inotropic response to afterload manifest early in the evolution of heart failure, we examined six anesthetized dogs instrumented with LV micromanometers, piezoelectric crystals, and coronary sinus catheters before and after 24 h of rapid ventricular pacing (RVP). After autonomic blockade, the end-systolic pressure-volume relation (ESPVR), myocardial O(2) consumption (MVO(2)), and LV pressure-volume area (PVA) were defined at several different afterloads produced by graded infusions of phenylephrine. Short-term RVP resulted in reduced preload with proportionate reductions in stroke work and the maximum first derivative of LV pressure but with no significant reduction in baseline LV contractile state. In response to increased afterload, the baseline ESPVR shifted to the left with maintained end-systolic elastance (E(es)). In contrast, after short-term RVP, in response to comparable increases in afterload, the ESPVR displayed reduced E(es) (P < 0.05) and significantly less leftward shift compared with control (P < 0.05). Compared with the control MVO(2)-PVA relation, short-term RVP significantly increased the MVO(2) intercept (P < 0.05) with no change in slope. These results indicate that short-term RVP produces attenuation of afterload-induced enhancement of LV performance and increases energy consumption for nonmechanical processes with maintenance of contractile efficiency, suggesting that early in the development of tachycardia heart failure, there is blunting of length-dependent activation and increased O(2) requirements for excitation-contraction coupling, basal metabolism, or both. Rather than being adaptive mechanisms, these abnormalities may be primary defects involved in the progression of the heart failure phenotype.
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Kurt, C
2015-09-01
This study aimed to compare the effect of local vibration (LV) and whole body vibration (WBV) on lower body flexibility and to assess whether vibration treatments were more effective than traditionally used static and dynamic stretching methods. Twenty-four well-trained male combat athletes (age: 22.7 ± 3.3 years) performed four exercise protocols - LV (30 Hz, 4 mm), WBV (30 Hz, 4 mm), static stretching (SS), and dynamic stretching (DS) - in four sessions of equal duration 48 hours apart in a randomized, balanced order. During a 15-minute recovery after each protocol, subjects performed the stand and reach test (S&R) at the 15th second and the 2(nd), 4(th), 6(th), 8(th), 10(th) and 15(th) minute. There was a similar change pattern in S&R scores across the 15-minute recovery after each protocol (p = 0.572), remaining significantly elevated throughout the recovery. A significant main protocol effect was found for absolute change in S&R scores relative to baseline (p = 0.015). These changes were statistically greater in LV than WBV and DS. Changes in SS were not significantly different from LV, but were consistently lower than LV with almost moderate effect sizes. After LV, a greater percentage of subjects increased flexibility above the minimum detectable change compared to other protocols. Subjects with high flexibility (n = 12) benefited more from LV compared with other methods (effect size ≥ 0.862). In conclusion, LV was an effective alternative exercise modality to acutely increase lower extremity flexibility for well-trained athletes compared with WBV and traditional stretching exercises.
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Stiermaier, Thomas; Pöss, Janine; Eitel, Charlotte; de Waha, Suzanne; Fuernau, Georg; Desch, Steffen; Thiele, Holger; Eitel, Ingo
2018-05-16
Left ventricular hypertrophy (LVH) has been suggested as a determinant of outcome in patients with ST-segment elevation myocardial infarction (STEMI). However, available data are inconclusive and the underlying mechanisms remain unclear. Therefore, the aim of this study was to evaluate the impact of LVH on myocardial injury and clinical outcome in a large multicenter STEMI population. Cardiovascular magnetic resonance was performed in 795 patients within 10 days after STEMI to assess left ventricular (LV) mass and parameters of myocardial injury. Gender-specific cutoff values of indexed LV mass were used to define LVH (67 g/m 2 for men and 61 g/m 2 for women). Rates of major adverse cardiac events (MACE) were determined at 12-month follow-up. LVH was present in 438 patients (55%) and associated with a significantly larger infarct size [18.3% of LV mass (%LV) versus 14.0%LV; p < 0.01], a lower myocardial salvage index (47.8 versus 54.4; p < 0.01), larger extent of microvascular obstruction (0.4 versus 0%LV; p < 0.01) and lower LV ejection fraction (47.9 versus 53.2%; p < 0.01) compared to STEMI patients without LVH. The effect of LVH on LV ejection fraction, infarct size and myocardial salvage index remained statistically significant after adjustment for baseline characteristics (p < 0.01 for all). MACE rates at 12 months were numerically higher in patients with versus without LVH without reaching statistical significance (7.5 versus 5.6%; p = 0.32). In STEMI patients, LVH is associated with more pronounced structural and functional alterations in CMR imaging as an indicator for adverse clinical outcomes in STEMI survivors.
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Zelveian, P A; Buniatian, M S; Oshchenkova, E V; Rogoza, A N; Sergakova, L M
2002-01-01
To study correlations between structural changes of the left ventricle (LV) in patients with mild and moderate arterial hypertension (AH) and severity of hypoxic night episodes. The examination of 50 patients (mean age 52 +/- 1 year) with mild and moderate hypertension included echocardiographic measurement of LV myocardial mass, calculation of LV myocardial mass index. LV hypertrophy was stated in the index 125 g/m2 for men and 110 g/m2 for women. 24-h monitoring of arterial pressure (TM-2425) and night monitoring of hemoglobin saturation of arterial blood with oxygen (SaO2) using pulsoxymeter NONIN 8500M were made. The data processing was performed with the use of original program ARM-SaO2. Dissaturation was stated if SaO2 fell by 4% and more compared to the previous stable level at initial SaO2 level above 90%. The patients were divided into two groups according to the number of dissaturation episodes: group 1 (more than 20 dissaturation episodes) and group 2 (less than 20 episodes). The groups were comparable by gender, duration of hypertension, body mass index, systolic and diastolic arterial pressure, heart rate. In group I, pulse arterial pressure, systolic arterial pressure load for 14 hours, day and night were significantly higher. Patients with dissaturation had a significantly higher LV myocardial mass and more frequent LV hypertrophy (128 +/- 6 and 106 +/- 5 g/m2 and 56 and 20%, respectively). The correlation and multifactor regression analysis showed a predictive value not only of the pressor parameters but also of indices of night hypoxia in relation to structural changes of LV myocardium. The presence of significant hypoxic episodes in sleep in AH patients indicates risk to develop structural changes of LV myocardium.
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Impact of obstructive sleep apnea on cardiac organ damage in patients with acute ischemic stroke.
Mattaliano, Paola; Lombardi, Carolina; Sangalli, Davide; Faini, Andrea; Corrà, Barbara; Adobbati, Laura; Branzi, Giovanna; Mariani, Davide; Silani, Vincenzo; Parati, Gianfranco
2018-06-01
Both obstructive sleep apnea (OSA) and cardiac organ damage have a crucial role in acute ischemic stroke. Our aim is to explore the relationship between OSA and cardiac organ damage in acute stroke patients. A total of 130 consecutive patients with acute ischemic stroke were enrolled. Patients underwent full multichannel 24-h polysomnography for evaluation of OSA and echocardiography to evaluate left ventricle (LV) mass index (LV mass/BSA, LV mass/height), thickness of interventricular septum (IVS) and posterior wall (LVPW), LV ejection fraction and left atrium enlargement. Information on occurrence of arterial hypertension and its treatment before stroke was obtained from patients' history. 61.9% (70) of patients, mostly men (67.1%), with acute stroke had OSA (AHI > 10). Patients with acute stroke and OSA showed a significant increase (P < 0.05) of LV mass index, IVS and LVPW thickness and a significant left atrial enlargement as compared with patients without OSA. LV ejection fraction was not significantly different in stroke patients with and without OSA and was within normal limits. No relationship was found among cardiac alterations, occurrence of OSA and history of hypertension. Acute stroke patients with OSA had higher LV mass and showed greater left atrial enlargement than patients without OSA. This study confirms the high prevalence of OSA in stroke patients, suggesting also an association between OSA and cardiac target organ damage. Our finding of structural LV abnormalities in acute stroke patients with OSA suggests a potential role of OSA as contributing factor in determining both cerebrovascular and cardiac damage, even in absence of clear link with a history of blood pressure elevation.
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Maruggi, Giulietta; Porcellini, Simona; Facchini, Giulia; Perna, Serena K; Cattoglio, Claudia; Sartori, Daniela; Ambrosi, Alessandro; Schambach, Axel; Baum, Christopher; Bonini, Chiara; Bovolenta, Chiara; Mavilio, Fulvio; Recchia, Alessandra
2009-01-01
The integration characteristics of retroviral (RV) vectors increase the probability of interfering with the regulation of cellular genes, and account for a tangible risk of insertional mutagenesis in treated patients. To assess the potential genotoxic risk of conventional or self-inactivating (SIN) γ-RV and lentiviral (LV) vectors independently from the biological consequences of the insertion event, we developed a quantitative assay based on real-time reverse transcriptase—PCR on low-density arrays to evaluate alterations of gene expression in individual primary T-cell clones. We show that the Moloney leukemia virus long terminal repeat (LTR) enhancer has the strongest activity in both a γ-RV and a LV vector context, while an internal cellular promoter induces deregulation of gene expression less frequently, at a shorter range and to a lower extent in both vector types. Downregulation of gene expression was observed only in the context of LV vectors. This study indicates that insertional gene activation is determined by the characteristics of the transcriptional regulatory elements carried by the vector, and is largely independent from the vector type or design. PMID:19293778
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Workup and management of patients with frequent premature ventricular contractions.
Giles, Katie; Green, Martin S
2013-11-01
Premature ventricular contractions (PVCs) are a frequently encountered entity in clinical cardiology. They rarely affect prognosis or management. However, they might produce bothersome symptoms and, in select individuals with a high PVC burden, they might contribute to left ventricular (LV) dysfunction. Workup of patients with very frequent PVCs consists of a thorough history and physical examination to screen for underlying cardiac disease and potential triggers. Routine investigations include a standard 12-lead electrocardiogram, as well as an echocardiogram. A Holter monitor should be performed in those with severe symptoms, a history of syncope, or a malignant family history. Exercise stress testing has a role in evaluating for ischemia and in the assessment of patients with exertional symptoms. More advanced testing is not warranted if these initial investigations are reassuring. Referral to an arrhythmia specialist should be considered in patients with LV dysfunction whose PVC burden exceeds 15%. Frequent ventricular ectopy represents a rare, but reversible cause of LV dysfunction and these patients should be further evaluated for possible catheter ablation. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Schober, Karsten E; Fuentes, Virginia Luis
2002-05-01
To evaluate left ventricular (LV) diastolic function in boxer dogs with aortic stenosis (AS). LV relaxation, elastic recoil, filling and stiffness have been found to be abnormal in people with AS and were related to disease severity, clinical signs and prognosis. 2-D, M-mode and Doppler echocardiography was done in 74 boxers with AS (55 with mild AS, 7 with moderate AS and 12 with severe AS) and compared with reference values from 66 normal boxers. Measurements included isovolumic relaxation time (IVRT), peak early (E) and late (A) transmitral filling velocities, mitral E wave deceleration time, peak systolic, and early and late (AR) diastolic pulmonary wenous flow velocities and related variables. In addition, left atrial (LA) function, LV dimensions and hypertrophy and LV systolic performance were assessed. Eight dogs (15%) with mild AS had abnormal LV diastolic function, compared with 16 dogs (84%) with moderate or severe AS. Two dogs (3%) had also systolic abnormalities. The flow pattern of delayed relaxation, pseudonormal mitral inflow and restrictive flow were found in 10, 11 and 3 dogs, respectively. IVRT and E:A were heterogeneous in dogs with moderate or severe AS, being either high, normal, or low. Peak AR velocity was significantly higher (p
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Olivotto, Iacopo; Maron, Martin S; Autore, Camillo; Lesser, John R; Rega, Luigi; Casolo, Giancarlo; De Santis, Marcello; Quarta, Giovanni; Nistri, Stefano; Cecchi, Franco; Salton, Carol J; Udelson, James E; Manning, Warren J; Maron, Barry J
2008-08-12
Our aim was to assess the distribution and clinical significance of left ventricular (LV) mass in patients with hypertrophic cardiomyopathy (HCM). Hypertrophic cardiomyopathy is defined echocardiographically by unexplained left ventricular wall thickening. Left ventricular mass, quantifiable by modern cardiovascular magnetic resonance techniques, has not been systematically assessed in this disease. In 264 HCM patients (age 43 +/- 18 years; 75% men), LV mass by cardiovascular magnetic resonance was measured, indexed by body surface area, and compared with that in 606 healthy control subjects. The LV mass index in HCM patients significantly exceeded that of control subjects (104 +/- 40 g/m(2) vs. 61 +/- 10 g/m(2) in men and 89 +/- 33 g/m(2) vs. 47 +/- 7 g/m(2) in women; both p < 0.0001). However, values were within the normal range (< or = mean +2 SDs for control subjects) in 56 patients (21%), and only mildly increased (mean +2 to 3 SDs) in 18 (16%). The LV mass index showed a modest relationship to maximal LV thickness (r(2) = 0.38; p < 0.001), and was greater in men (104 +/- 40 g/m(2) vs. 89 +/- 33 g/m(2) in women; p < 0.001) and in patients with resting outflow obstruction (121 +/- 43 g/m(2) vs. 96 +/- 37 g/m(2) in nonobstructives; p < 0.001). During a 2.6 +/- 0.7-year follow-up, markedly increased LV mass index proved more sensitive in predicting outcome (100%, with 39% specificity), whereas maximal wall thickness >30 mm was more specific (90%, with 41% sensitivity). In distinction to prior perceptions, LV mass index was normal in about 20% of patients with definite HCM phenotype. Therefore, increased LV mass is not a requirement for establishing the clinical diagnosis of HCM. The LV mass correlated weakly with maximal wall thickness, and proved more sensitive in predicting outcome.
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Estimation of the effects of multipoint pacing on battery longevity in routine clinical practice.
Akerström, Finn; Narváez, Irene; Puchol, Alberto; Pachón, Marta; Martín-Sierra, Cristina; Rodríguez-Mañero, Moisés; Rodríguez-Padial, Luis; Arias, Miguel A
2017-09-23
Multipoint pacing (MPP) permits simultaneous multisite pacing of the left ventricle (LV); initial studies suggest haemodynamic and clinical benefits over conventional (single LV site) cardiac resynchronization therapy (CRT). The aim of this study was to estimate the impact of MPP activation on battery longevity in routine clinical practice. Patient (n = 46) and device data were collected from two centres at least 3 months after MPP-CRT device implantation. Multipoint pacing programming was based on the maximal possible anatomical LV1/LV2 separation according to three predefined LV pacing capture threshold (PCT) cut-offs (≤1.5 V; ≤4.0 V; and ≤6.5 V). Estimated battery longevity was calculated using the programmed lower rate limit, lead impedances, outputs, and pacing percentages. Relative to the longevity for conventional CRT using the lowest PCT (8.9 ± 1.2 years), MPP activation significantly shortened battery longevity for all three PCT cut-offs (≤1.5 V, -5.6%; ≤4.0 V, -16.9%; ≤6.5 V, -21.3%; P's <0.001). When compared with conventional CRT based on longest right ventricle-LV delay (8.3 ± 1.3 years), battery longevity was significantly shortened for the MPP ≤ 4.0 V and ≤6.5 V cut-offs (-10.8 and -15.7%, respectively; P's <0.001). Maximal LV1/LV2 spacing was possible in 23.9% (≤1.5 V), 56.5% (≤4.0 V), and 69.6% (≤6.5 V) of patients. Multipoint pacing activation significantly reduces battery longevity compared with that for conventional CRT configuration. When reasonable MPP LV vector PCTs (≤4.0 V) are achieved, the decrease in battery longevity is relatively small which may prompt the clinician to activate MPP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
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NASA Technical Reports Server (NTRS)
Qin, J. X.; Shiota, T.; McCarthy, P. M.; Firstenberg, M. S.; Greenberg, N. L.; Tsujino, H.; Bauer, F.; Travaglini, A.; Hoercher, K. J.; Buda, T.;
2000-01-01
BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.
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Bunting, Ethan; Lambrakos, Litsa; Kemper, Paul; Whang, William; Garan, Hasan; Konofagou, Elisa
2017-01-01
Current electrocardiographic and echocardiographic measurements in heart failure (HF) do not take into account the complex interplay between electrical activation and local wall motion. The utilization of novel technologies to better characterize cardiac electromechanical behavior may lead to improved response rates with cardiac resynchronization therapy (CRT). Electromechanical wave imaging (EWI) is a noninvasive ultrasound-based technique that uses the transient deformations of the myocardium to track the intrinsic EW that precedes myocardial contraction. In this paper, we investigate the performance and reproducibility of EWI in the assessment of HF patients and CRT. EWI acquisitions were obtained in five healthy controls and 16 HF patients with and without CRT pacing. Responders (n = 8) and nonresponders (n = 8) to CRT were identified retrospectively on the basis of left ventricular (LV) reverse remodeling. Electromechanical activation maps were obtained in all patients and used to compute a quantitative parameter describing the mean LV lateral wall activation time (LWAT). Mean LWAT was increased by 52.1 ms in HF patients in native rhythm compared to controls (P < 0.01). For all HF patients, CRT pacing initiated a different electromechanical activation sequence. Responders exhibited a 56.4-ms ± 28.9-ms reduction in LWAT with CRT pacing (P < 0.01), while nonresponders showed no significant change. In this initial feasibility study, EWI was capable of characterizing local cardiac electromechanical behavior as it pertains to HF and CRT response. Activation sequences obtained with EWI allow for quantification of LV lateral wall electromechanical activation, thus providing a novel method for CRT assessment. © 2016 Wiley Periodicals, Inc.
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Goo, Hyun Woo; Park, Sang-Hyub
2015-12-01
To assess agreement between two semi-automatic, three-dimensional (3D) computed tomography (CT) ventricular volumetry methods with different user interactions in patients with congenital heart disease. In 30 patients with congenital heart disease (median age 8 years, range 5 days-33 years; 20 men), dual-source, multi-section, electrocardiography-synchronized cardiac CT was obtained at the end-systolic (n = 22) and/or end-diastolic (n = 28) phase. Nineteen left ventricle end-systolic (LV ESV), 28 left ventricle end-diastolic (LV EDV), 22 right ventricle end-systolic (RV ESV), and 28 right ventricle end-diastolic volumes (RV EDV) were successfully calculated using two semi-automatic, 3D segmentation methods with different user interactions (high in method 1, low in method 2). The calculated ventricular volumes of the two methods were compared and correlated. A P value <0.05 was considered statistically significant. LV ESV (35.95 ± 23.49 ml), LV EDV (88.76 ± 61.83 ml), and RV ESV (46.87 ± 47.39 ml) measured by method 2 were slightly but significantly smaller than those measured by method 1 (41.25 ± 26.94 ml, 92.20 ± 62.69 ml, 53.61 ± 50.08 ml for LV ESV, LV EDV, and RV ESV, respectively; P ≤ 0.02). In contrast, no statistically significant difference in RV EDV (122.57 ± 88.57 ml in method 1, 123.83 ± 89.89 ml in method 2; P = 0.36) was found between the two methods. All ventricular volumes showed very high correlation (R = 0.978, 0.993, 0.985, 0.997 for LV ESV, LV EDV, RV ESV, and RV EDV, respectively; P < 0.001) between the two methods. In patients with congenital heart disease, 3D CT ventricular volumetry shows good agreement and high correlation between the two methods, but method 2 tends to slightly underestimate LV ESV, LV EDV, and RV ESV.
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Fairbairn, Timothy A; Steadman, Christopher D; Mather, Adam N; Motwani, Manish; Blackman, Daniel J; Plein, Sven; McCann, Gerry P; Greenwood, John P
2013-01-01
Objective To compare the effects of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) on aortic valve haemodynamics, ventricular reverse remodelling and myocardial fibrosis (MF) by cardiovascular magnetic resonance (CMR) imaging. Design A 1.5 T CMR scan was performed preoperatively and 6 months postoperatively. Setting University hospitals of Leeds and Leicester, UK. Patients 50 (25 TAVI, 25 SAVR; age 77±8 years) high-risk severe symptomatic aortic stenosis (AS) patients. Main outcome measures Valve haemodynamics, ventricular volumes, ejection fraction (EF), mass and MF. Results Patients were matched for gender and AS severity but not for age (80±6 vs 73±7 years, p=0.001) or EuroSCORE (22±14 vs 7±3, p<0.001). Aortic valve mean pressure gradient decreased to a greater degree post-TAVI compared to SAVR (21±8 mm Hg vs 35±13 mm Hg, p=0.017). Aortic regurgitation reduced by 8% in both groups, only reaching statistical significance for TAVI (p=0.003). TAVI and SAVR improved (p<0.05) left ventricular (LV) end-systolic volumes (46±18 ml/m2 vs 41±17 ml/m2; 44±22 ml/m2 vs32±6 ml/m2) and mass (83±20 g/m2 vs 65±15 g/m2; 74±11 g/m2 vs 59±8 g/m2). SAVR reduced end-diastolic volumes (92±19 ml/m2 vs 74±12 ml/m2, p<0.001) and TAVI increased EF (52±12% vs 56±10%, p=0.01). MF reduced post-TAVI (10.9±6% vs 8.5±5%, p=0.03) but not post-SAVR (4.2±2% vs 4.1±2%, p=0.98). Myocardial scar (p≤0.01) and baseline ventricular volumes (p<0.001) were the major predictors of reverse remodelling. Conclusions TAVI was comparable to SAVR at LV reverse remodelling and superior at reducing the valvular pressure gradient and MF. Future work should assess the prognostic importance of reverse remodelling and fibrosis post-TAVI to aid patient selection. PMID:23749779
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Mao, Shuai; Zhang, Xiaoxuan; Shao, Biying; Hu, Xiyan; Hu, Yanan; Li, Winny; Guo, Liheng; Zhang, Minzhou
2016-06-01
Left ventricular (LV) remodeling following myocardial infarction (MI) is an established prognostic factor for adverse cardiovascular events and the leading cause of heart failure. Empirical observations have suggested that Baduanjin exercise, an important component of traditional Chinese Qigong, may exert potential benefits on cardiopulmonary function. However, the impact of a Baduanjin exercise-based cardiac rehabilitation program for patients recovering from a recent MI has yet to be assessed. The aim of this trial is to evaluate the potential role of Baduanjin exercise in preventing the maladaptive progression to adverse LV remodeling in patients post-MI. A total of 110 clinically stable patients following an MI after undergoing successful infarct-related artery reperfusion will be randomly assigned to the Baduanjin exercise group or usual exercise control group. In addition to usual physical activity, participants in the Baduanjin exercise group will participate in a 45 min Baduanjin exercise training session twice a week, for a total of 12 weeks. The primary endpoint will be the percentage change in LV end-diastolic volume index (LVEDVi) assessed using echocardiography from baseline to 6 months. The results of this study may provide novel evidence on the efficacy of Baduanjin exercise therapy in post-MI patients in reversing adverse LV remodeling and improving clinical outcome. Clinical Trials.gov: NCT02693795.
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Imbriaco, M; Pisani, A; Spinelli, L; Cuocolo, A; Messalli, G; Capuano, E; Marmo, M; Liuzzi, R; Visciano, B; Cianciaruso, B; Salvatore, M
2009-07-01
Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. This study aimed to assess the long-term effects of ERT with recombinant alpha-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease. Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson-Fabry disease.
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Redetzke, Rebecca A.; Gerdes, A. Martin
2012-01-01
Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390
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Kueh, Shaw-Hua Anthony; Gabriel, Ruvin S; Lund, Mayanna; Sutton, Tim; Bradley, Joshua; Kerr, Andrew J; Looi, Jen-Li
2016-11-01
Amphetamine-associated cardiomyopathy (AAC) is becoming an increasingly recognised entity. The characteristics and outcomes of these patients are poorly understood. Thirty patients admitted with heart failure and echocardiographic evidence of cardiomyopathy between 2005 and 2014 and who had a documented history of amphetamine abuse that was considered an important factor in the causation of their cardiomyopathy were retrospectively identified. Mean age at presentation was 40±10 years with a male predominance (n=25, 83%). The majority were of indigenous Maori ethnicity. At presentation, four patients were in cardiogenic shock. Five patients required intensive care unit (ICU) admission for inotropic support and mechanical ventilation. Fifteen had severe left ventricular (LV) dilation (mean LV end-diastolic dimension 6.8±1.0cm) and all patients had severe LV dysfunction (mean LV ejection fraction 22±8%). Despite optimal heart failure therapy, LV size remained significantly dilated with minimal improvement in LV function. During median follow-up of 18 months, five patients died from end-stage heart failure and 17 had at least one readmission with decompensated heart failure. Amphetamine-associated cardiomyopathy was seen predominantly in young indigenous Maori men. They presented with severe cardiomyopathy, often requiring ICU admission. Severe LV dilation and significant LV dysfunction persisted despite treatment and mortality was high. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
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Rapid and sensitive insulated isothermal PCR for point-of-need feline leukaemia virus detection.
Wilkes, Rebecca P; Anis, Eman; Dunbar, Dawn; Lee, Pei-Yu A; Tsai, Yun-Long; Lee, Fu-Chun; Chang, Hsiao-Fen G; Wang, Hwa-Tang T; Graham, Elizabeth M
2018-04-01
Objectives Feline leukaemia virus (FeLV), a gamma retrovirus, causes diseases of the feline haematopoietic system that are invariably fatal. Rapid and accurate testing at the point-of-need (PON) supports prevention of virus spread and management of clinical disease. This study evaluated the performance of an insulated isothermal PCR (iiPCR) that detects proviral DNA, and a reverse transcription (RT)-iiPCR that detects both viral RNA and proviral DNA, for FeLV detection at the PON. Methods Mycoplasma haemofelis, feline coronavirus, feline herpesvirus, feline calicivirus and feline immunodeficiency virus were used to test analytical specificity. In vitro transcribed RNA, artificial plasmid, FeLV strain American Type Culture Collection VR-719 and a clinical FeLV isolate were used in the analytical sensitivity assays. A retrospective study including 116 clinical plasma and serum samples that had been tested with virus isolation, real-time PCR and ELISA, and a prospective study including 150 clinical plasma and serum samples were implemented to evaluate the clinical performances of the iiPCR-based methods for FeLV detection. Results Ninety-five percent assay limit of detection was calculated to be 16 RNA and five DNA copies for the RT-iiPCR, and six DNA copies for the iiPCR. Both reactions had analytical sensitivity comparable to a reference real-time PCR (qPCR) and did not detect five non-target feline pathogens. The clinical performance of the RT-iiPCR and iiPCR had 98.82% agreement (kappa[κ] = 0.97) and 100% agreement (κ = 1.0), respectively, with the qPCR (n = 85). The agreement between an automatic nucleic extraction/RT-iiPCR system and virus isolation to detect FeLV in plasma or serum was 95.69% (κ = 0.95) and 98.67% (κ = 0.85) in a retrospective (n = 116) and a prospective (n = 150) study, respectively. Conclusions and relevance These results suggested that both RT-iiPCR and iiPCR assays can serve as reliable tools for PON FeLV detection.
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Innocent, Neal; Livingstone, Phil D.; Hone, Arik; Kimura, Atsuko; Young, Tracey; Whiteaker, Paul; McIntosh, J. Michael; Wonnacott, Susan
2008-01-01
A recently developed α-conotoxin, α-CtxArIB[V11L,V16D] is a potent and selective competitive antagonist at rat recombinant α7 nicotinic acetylcholine receptors (nAChRs), making it an attractive probe for this receptor subtype. α7 nAChRs are potential therapeutic targets that are widely expressed in both neuronal and non-neuronal tissues where they are implicated in a variety of functions. Here we evaluate this toxin at rat and human native nAChRs. Functional α7 nAChR responses were evoked by choline plus the allosteric potentiator PNU-120596 in rat PC12 cells and human SHSY5Y cells loaded with calcium indicators. α-CtxArIB[V11L,V16D] specifically inhibited α7 nAChR-mediated increases in Ca2+ in PC12 cells. Responses to other stimuli (5-iodo-A-85380, nicotine or KCl) that did not activate α7 nAChRs were unaffected. Human α7 nAChRs were also sensitive to α-CtxArIB[V11L,V16D]: ACh-evoked currents in X. laevis oocytes expressing human α7 nAChRs were inhibited by α-CtxArIB[V11L,V16D] (IC50 3.4 nM) in a slowly reversible manner, with full recovery taking 15 min. This is consistent with the timecourse of recovery from blockade of rat α7 nAChRs in PC12 cells. α-CtxArIB[V11L,V16D] inhibited human native α7 nAChRs in SHSY5Y cells, activated by either choline or AR-R17779 plus PNU-120596. Rat brain α7 nAChRs contribute to dopamine release from striatal minces: α-CtxArIB[V11L,V16D] (300 nM) selectively inhibited choline-evoked dopamine release without affecting responses evoked by nicotine that activates heteromeric nAChRs. This study establishes that α-CtxArIB[V11L,V16D] selectively inhibits human and rat native α7 nAChRs with comparable potency, making this a potentially useful antagonist for investigating α7 nAChR functions. PMID:18664588
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Solomon, Scott D; Appelbaum, Evan; Manning, Warren J; Verma, Anil; Berglund, Tommy; Lukashevich, Valentina; Cherif Papst, Cheraz; Smith, Beverly A; Dahlöf, Björn
2009-02-03
Left ventricular (LV) hypertrophy, a marker of cardiac end-organ damage, is associated with an increased risk of cardiovascular morbidity and mortality. Inhibitors of the renin-angiotensin-aldosterone system may reduce LV mass to a greater extent than other antihypertensive agents. We compared the effect of aliskiren, the first orally active direct renin inhibitor, the angiotensin-receptor blocker losartan, and their combination on the reduction of LV mass in hypertensive patients. We randomized 465 patients with hypertension, increased ventricular wall thickness, and body mass index >25 kg/m(2) to receive aliskiren 300 mg, losartan 100 mg, or their combination daily for 9 months. Patients were treated to standard blood pressure targets with add-on therapy, excluding other inhibitors of the renin-angiotensin-aldosterone system and beta-blockers. Patients underwent cardiovascular magnetic resonance imaging for assessment of LV mass at baseline and at study completion. The primary objective was to compare change in LV mass index from baseline to follow-up in the combination and losartan arms; the secondary objective was to determine whether aliskiren was noninferior to losartan in reducing LV mass index from baseline to follow-up. Systolic and diastolic blood pressures were reduced similarly in all treatment groups (6.5+/-14.9/3.8+/-10.1 mm Hg in the aliskiren group; 5.5+/-15.6/3.7+/-10.7 mm Hg in the losartan group; 6.6+/-16.6/4.6+/-10.5 mm Hg in the combination arm; P<0.0001 within groups, P=0.81 between groups). LV mass index was reduced significantly from baseline in all treatment groups (4.9-, 4.8-, and 5.8 g/m(2) reductions in the aliskiren, losartan, and combination arms, respectively; P<0.0001 for all treatment groups). The reduction in LV mass index in the combination group was not significantly different from that with losartan alone (P=0.52). Aliskiren was as effective as losartan in reducing LV mass index (P<0.0001 for noninferiority). Safety and tolerability were similar across all treatment groups. Aliskiren was as effective as losartan in promoting LV mass regression. Reduction in LV mass with the combination of aliskiren plus losartan was not significantly different from that with losartan monotherapy, independent of blood pressure lowering. These findings suggest that aliskiren was as effective as an angiotensin receptor blocker in attenuating this measure of myocardial end-organ damage in hypertensive patients with LV hypertrophy.
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Cho, Young Sun; Hwang, Seo Jung; Kim, Hyo Jin
2017-01-01
Background To evaluate the outcomes of left ventricular (LV) function according to treatment response for a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Methods Echocardiograms of 21 preterm infants born at gestational age < 31 weeks obtained at term-equivalent age were retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation after failure of pharmacological closure (ligation group) and 6 experienced successful pharmacological closure (medication group). Six preterm infants without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal systolic strain (ε) of each infant was retrospectively obtained from echocardiograms using velocity vector imaging, along with neonatal outcomes. Results Pharmacological closures were attempted at postnatal day 2–3. In the ligation group, the median postnatal age at ligation was 20 days. In the ligation group, LV peak longitudinal systolic ε was significantly decreased at term-equivalent age compared to the other groups. Between the medication and no-hsPDA groups, LV peak longitudinal systolic ε did not differ significantly. Among the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC) showed significantly decreased LV peak longitudinal systolic ε compared to the infants who did not experience NEC . Conclusion We speculate that in preterm infants with an hsPDA, in cases of medical treatment failure, early PDA ligation at less than 20 days of postnatal age would be beneficial for preserving LV systolic function. PMID:29333220
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Enzyme replacement therapy with agalsidase beta improves cardiac involvement in Fabry's disease.
Spinelli, L; Pisani, A; Sabbatini, M; Petretta, M; Andreucci, M V; Procaccini, D; Lo Surdo, N; Federico, S; Cianciaruso, B
2004-08-01
Fabry's disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase that results in an accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. Fabry cardiomyopathy, characterized by progressive severe concentric left ventricular (LV) hypertrophy, is very frequent and is the most important cause of death in affected patients. Enzyme replacement therapy (ERT) allows a specific treatment for this disease, however, there are very few data on the effectiveness of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were studied on basal condition and after 6 and 12 months of treatment with algasidase beta (Fabrazyme). A complete clinical, electrocardiographic and echocardiographic evaluation was performed in all patients. Interpretable Doppler recordings of transmitral flow and pulmonary flow velocity curves were also acquired. At baseline, the patients with Fabry's disease had increased LV septum and posterior wall thickness, normal LV fractional shortening, LV ejection fraction, normal Doppler parameters of mitral inflow but a duration of pulmonary vein flow velocity wave exceeding that of the mitral wave at atrial systole. ERT did not affect heart rate and arterial pressure. LV internal diameters did not change, there was a slight but not significant decrease in the LV posterior wall thickening and a progressive decrease in the interventricular septum thickening (p < 0.025) and in LV mass (p < 0.001) The difference in duration between pulmonary vein flow velocity wave and mitral wave at atrial systole significantly decreased (p < 0.001). These results suggest that ERT in patients with Fabry cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness. Copyright 2004 Blackwell Munksgaard
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Jankauskienė, Edita; Orda, Paulius; Barauskienė, Greta; Mickuvienė, Narseta; Brožaitienė, Julija; Vaškelytė, Jolanta Justina; Bunevičius, Robertas
2016-04-01
Low free triiodothyronine (fT3) levels following acute myocardial infarction (AMI) are associated with greater impairment in cardiac mechanics compared with patients with AMI who have normal values of thyroid hormones. The objectives are to investigate left ventricular (LV) function and mechanics during a 6-month follow-up after myocardial infarction and to evaluate their prognostic implication using two-dimensional (2D) echocardiography and 2D speckle-tracking echocardiography in patients with low fT3 levels. The study design is prospective cohort study. One hundred forty patients with first-onset AMI were grouped according to serum fT3 levels: low fT3 group (fT3 <3.2 pmol/L; n = 44) and control group (fT3 >3.2 pmol/L; n = 96). Low levels of fT3 were associated with greater LV diameters and LV end-diastolic volume, and decreased systolic LV function. Systolic apical and basal rotation, peak systolic global longitudinal strain and strain rate, and LV twist and torsion were significantly decreased in the low fT3 group. The prognostic implication for predicting low fT3 levels was evaluated using ROC analysis. LV end-diastolic diameter index is the most sensitive (94.12 %), but has low specificity (37.93 %; area = 0.659, p = 0.01). By contrast, LV end-systolic volume is the most specific (94.03 %), but has low sensitivity (26.32 %; area = 0.594, p = 0.04). Low fT3 levels are significantly associated with worse LV mechanics. Low fT3 levels are important for prediction of LV structure, function, rotation, and deformation parameters during the late post-myocardial infarction period.
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Gowing, Lucy; Forsey, Jonathan; Ramanujam, Paramanantham; Miller, Felicity; Stuart, A Graham; Williams, Craig A.
2015-01-01
Background left ventricular (LV) and right ventricular (RV) myocardial reserve during exercise in adolescents has not been directly characterized. The aim of this study was to quantify myocardial performance response to exercise by using two-dimensional (2-D) speckle tracking echocardiography and describe the relationship between myocardial reserve, respiratory, and metabolic exercise parameters. A total of 23 healthy boys and girls (mean age 13.2 ± 2.7 yr; stature 159.1 ± 16.4 cm; body mass 49.5 ± 16.6 kg; BSA 1.47 ± 0.33 m2) completed an incremental cardiopulmonary exercise test (25 W·3 min increments) with simultaneous acquisition of 2-D transthoracic echocardiography at rest, each exercise stage up to 100 W, and in recovery at 2 min and 10 min. Two-dimensional LV (LV Sl) and RV (RV Sl) longitudinal strain and LV circumferential strain (LV Sc) were analyzed to define the relationship between myocardial performance reserve and metabolic exercise parameters. Participants achieved a peak oxygen uptake (V̇o2peak) of 40.6 ± 8.9 ml·kg−1·min−1 and a work rate of 154 ± 42 W. LV Sl and LV Sc and RV Sl increased significantly across work rates (P < 0.05). LV Sl during exercise was significantly correlated to resting strain, V̇o2peak, oxygen pulse, and work rate (0.530 ≤ r ≤ 0.784, P < 0.05). This study identifies a positive and moderate relationship between LV and RV myocardial performance and metabolic parameters during exercise by using a novel methodology. Relationships detected present novel data directly describing myocardial adaptation at different stages of exercise and recovery that in the future can help directly assess cardiac reserve in patients with cardiac pathology. PMID:26475589
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Jeong, Young-Hoon; Yun, Tae-Jin; Song, Jong-Min; Park, Jung-Jun; Seo, Dong-Man; Koh, Jae-Kon; Lee, Se-Whan; Kim, Mi-Jeong; Kang, Duk-Hyun; Song, Jae-Kwan
2007-09-01
Left ventricular (LV) remodeling and predictors of LV systolic function late after closure of patent ductus arteriosus (PDA) in adults remain to be clearly demonstrated. In 45 patients with PDA, including 28 patients who received successful occlusion using the Amplatzer device (AD group) (AGA, Golden Valley, MN) and 17 patients who received surgical closure (OP group), echocardiography studies were performed before closure and 1 day (AD group) or within 7 days (OP group) after closure, and then were repeated at > or = 6 months (17 +/- 13 months). In both groups, LV ejection fraction (EF) and end-diastolic volume index were significantly decreased immediately after closure, whereas end-systolic volume index did not change. During the long-term follow-up period, end-systolic as well as end-diastolic volume indices decreased significantly in both groups and LV EF recovered compared to the immediate postclosure state. However, LV EF remained low compared to the preclosure state. Five patients (11.1%) including 3 patients in the AD group and 2 patients in the OP group showed persistent late LV systolic dysfunction (EF <50%). In stepwise, multiple logistic regression analysis, preclosure EF was the only independent predictor of late normal postclosure EF (odds ratio, 1.230; 95% CI, 1.054-1.434; P = .008). Receiver operating characteristic curve analysis showed that preclosure EF > or = 62% had a sensitivity of 72% and a specificity of 83% for predicting late normal LV EF after closure. Left ventricular EF remains low late after PDA closure compared with preclosure state in adults. Preclosure LV EF is the best index to predict late postclosure LV EF.
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Mafi Rad, Masih; Blaauw, Yuri; Dinh, Trang; Pison, Laurent; Crijns, Harry J; Prinzen, Frits W; Vernooy, Kevin
2014-11-01
Current targeted left ventricular (LV) lead placement strategy is directed at the latest activated region during intrinsic activation. However, cardiac resynchronization therapy (CRT) is most commonly applied by simultaneous LV and right ventricular (RV) pacing without contribution from intrinsic conduction. Therefore, targeting the LV lead to the latest activated region during RV pacing might be more appropriate. We investigated the difference in LV electrical activation sequence between left bundle-branch block (LBBB) and RV apex (RVA) pacing using coronary venous electro-anatomic mapping (EAM). Twenty consecutive CRT candidates with LBBB underwent intra-procedural coronary venous EAM during intrinsic activation and RVA pacing using EnSite NavX. Left ventricular lead placement was aimed at the latest activated region during LBBB according to current recommendations. In all patients, LBBB was associated with a circumferential LV activation pattern, whereas RVA pacing resulted in activation from the apex of the heart to the base. In 10 of 20 patients, RVA pacing shifted the latest activated region relative to LBBB. In 18 of 20 patients, the LV lead was successfully positioned in the latest activated region during LBBB. For the whole study population, LV lead electrical delay, expressed as percentage of QRS duration, was significantly shorter during RVA pacing than during LBBB (72 ± 13 vs. 82 ± 5%, P = 0.035). Right ventricular apex pacing alters LV electrical activation pattern in CRT patients with LBBB, and shifts the latest activated region in a significant proportion of these patients. These findings warrant reconsideration of the current practice of LV lead targeting for CRT. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.
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The influence of adrenergic stimulation on sex differences in left ventricular twist mechanics.
Williams, Alexandra M; Shave, Rob E; Cheyne, William S; Eves, Neil D
2017-06-15
Sex differences in left ventricular (LV) mechanics occur during acute physiological challenges; however, it is unknown whether sex differences in LV mechanics are fundamentally regulated by differences in adrenergic control. Using two-dimensional echocardiography and speckle tracking analysis, this study compared LV mechanics in males and females matched for LV length during post-exercise ischaemia (PEI) and β 1 -adrenergic receptor blockade. Our data demonstrate that while basal rotation was increased in males, LV twist was not significantly different between the sexes during PEI. In contrast, during β 1 -adrenergic receptor blockade, LV apical rotation, twist and untwisting velocity were reduced in males compared to females. Significant relationships were observed between LV twist and LV internal diameter and sphericity index in females, but not males. These findings suggest that LV twist mechanics may be more sensitive to alterations in adrenergic stimulation in males, but more highly influenced by ventricular structure and geometry in females. Sex differences in left ventricular (LV) mechanics exist at rest and during acute physiological stress. Differences in cardiac autonomic and adrenergic control may contribute to sex differences in LV mechanics and LV haemodynamics. Accordingly, this study aimed to investigate sex differences in LV mechanics with altered adrenergic stimulation achieved through post-handgrip-exercise ischaemia (PEI) and β 1 -adrenergic receptor (AR) blockade. Twenty males (23 ± 5 years) and 20 females (22 ± 3 years) were specifically matched for LV length (males: 8.5 ± 0.5 cm, females: 8.2 ± 0.6 cm, P = 0.163), and two-dimensional speckle-tracking echocardiography was used to assess LV structure and function at baseline, during PEI and following administration of 5 mg bisoprolol (β 1 -AR antagonist). During PEI, LV end-diastolic volume and stroke volume were increased in both groups (P < 0.001), as was end-systolic wall stress (P < 0.001). LV twist and apical rotation were not altered from baseline or different between the sexes; however, basal rotation increased in males (P = 0.035). During β 1 -AR blockade, LV volumes were unchanged but blood pressure and heart rate were reduced in both groups (P < 0.001). LV apical rotation (P = 0.036) and twist (P = 0.029) were reduced in males with β 1 -AR blockade but not females, resulting in lower apical rotation (males: 6.8 ± 2.1 deg, females: 8.8 ± 2.3 deg, P = 0.007) and twist (males: 8.6 ± 1.9 deg, females: 10.7 ± 2.8 deg, P = 0.008), and slower untwisting velocity (males: 68.2 ± 22.1 deg s -1 , females: 82.0 ± 18.7 deg s -1 , P = 0.046) compared to females. LV twist mechanics are reduced in males compared to females during reductions to adrenergic stimulation, providing preliminary evidence that LV twist mechanics may be more sensitive to adrenergic control in males than in females. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.
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Bonios, Michael J; Koliopoulou, Antigone; Wever-Pinzon, Omar; Taleb, Iosif; Stehlik, Josef; Xu, Weining; Wever-Pinzon, James; Catino, Anna; Kfoury, Abdallah G; Horne, Benjamin D; Nativi-Nicolau, Jose; Adamopoulos, Stamatis N; Fang, James C; Selzman, Craig H; Bax, Jeroen J; Drakos, Stavros G
2018-04-01
Impaired qualitative and quantitative left ventricular (LV) rotational mechanics predict cardiac remodeling progression and prognosis after myocardial infarction. We investigated whether cardiac rotational mechanics can predict cardiac recovery in chronic advanced cardiomyopathy patients. Sixty-three patients with advanced and chronic dilated cardiomyopathy undergoing implantation of LV assist device (LVAD) were prospectively investigated using speckle tracking echocardiography. Acute heart failure patients were prospectively excluded. We evaluated LV rotational mechanics (apical and basal LV twist, LV torsion) and deformational mechanics (circumferential and longitudinal strain) before LVAD implantation. Cardiac recovery post-LVAD implantation was defined as (1) final resulting LV ejection fraction ≥40%, (2) relative LV ejection fraction increase ≥50%, (iii) relative LV end-systolic volume decrease ≥50% (all 3 required). Twelve patients fulfilled the criteria for cardiac recovery (Rec Group). The Rec Group had significantly less impaired pre-LVAD peak LV torsion compared with the Non-Rec Group. Notably, both groups had similarly reduced pre-LVAD LV ejection fraction. By receiver operating characteristic curve analysis, pre-LVAD peak LV torsion of 0.35 degrees/cm had a 92% sensitivity and a 73% specificity in predicting cardiac recovery. Peak LV torsion before LVAD implantation was found to be an independent predictor of cardiac recovery after LVAD implantation (odds ratio, 0.65 per 0.1 degrees/cm [0.49-0.87]; P =0.014). LV rotational mechanics seem to be useful in selecting patients prone to cardiac recovery after mechanical unloading induced by LVADs. Future studies should investigate the utility of these markers in predicting durable cardiac recovery after the explantation of the cardiac assist device. © 2018 American Heart Association, Inc.
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Usefulness of Epicardial Area in the Short Axis to Identify Elevated Left Ventricular Mass in Men.
Fitzpatrick, Jesse K; Cohen, Beth E; Rosenblatt, Andrew; Shaw, Richard E; Schiller, Nelson B
2018-06-15
Left ventricular (LV) hypertrophy is strongly associated with increased cardiovascular morbidity and mortality. The 2-dimensional LV mass algorithms suffer from measurement variability that can lead to misclassification of patients with LV hypertrophy as normal, or vice versa. Among the 4 echocardiographic measurements required by the 2-dimensional LV mass algorithms, epicardial and endocardial area have the lowest interobserver variation and could be used to corroborate LV mass calculations. We sought cut-off values that are able to discriminate between elevated and normal LV mass based on endocardial or epicardial area alone. Using data from 664 men enrolled in the Mind Your Heart Study, we calculated the correlation of LV mass index with epicardial area and endocardial area. We then used receiver operator characteristic curves to identify epicardial and endocardial area cut-points that could discriminate subjects with normal LV mass and LV hypertrophy. LV mass index was more strongly correlated with epicardial area compared with endocardial area, r = 0.70 versus r = 0.27, respectively. Epicardial area had a significantly higher area under the receiver operator characteristic curve (p <0.001) compared with endocardial area, 0.90 (95% confidence interval 0.86 to 0.93) versus 0.63 (95% confidence interval 0.57 to 0.71). An epicardial area cut-point of ≥38.0 cm 2 corresponded to a sensitivity of 95.0% and specificity of 54.4% for detecting LV hypertrophy. In conclusion, epicardial area showed promise as a method of rapid screening for LV hypertrophy and could be used to validate formal LV mass calculations. Copyright © 2018 Elsevier Inc. All rights reserved.
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Bolin, Lisa L; Ahmad, Shamim; Levy, Laura S
2011-10-15
Feline leukemia virus (FeLV) is a natural retrovirus of domestic cats associated with degenerative, proliferative and malignant diseases. Studies of FeLV infection in a cohort of naturally infected cats were undertaken to examine FeLV variation, the selective pressures operative in FeLV infection that lead to predominance of natural variants, and the consequences for infection and disease progression. A unique variant, designated FeLV-945, was identified as the predominant isolate in the cohort and was associated with non-T-cell diseases including multicentric lymphoma. FeLV-945 was assigned to the FeLV-A subgroup based on sequence analysis and receptor utilization, but was shown to differ in sequence from a prototype member of FeLV-A, designated FeLV-A/61E, in the long terminal repeat (LTR) and the surface glycoprotein gene (SU). A unique sequence motif in the FeLV-945 LTR was shown to function as a transcriptional enhancer and to confer a replicative advantage. The FeLV-945 SU protein was observed to differ in sequence as compared to FeLV-A/61E within functional domains known to determine receptor selection and binding. Experimental infection of newborn cats was performed using wild type FeLV-A/61E or recombinant FeLV-A/61E in which the LTR (61E/945L) or LTR and SU (61E/945SL) were exchanged for that of FeLV-945. Infection with either FeLV-A/61E or 61E/945L resulted in T-cell lymphoma of the thymus, although 61E/945L caused disease significantly more rapidly. In contrast, infection with 61E/945SL resulted in the rapid induction of a multicentric lymphoma of B-cell origin, thus recapitulating the outcome of natural infection and implicating FeLV-945 SU as a determinant of disease outcome. Recombinant FeLV-B was detected infrequently and at low levels in multicentric lymphomas, and was thereby not implicated in disease induction. Preliminary studies of receptor interaction indicated that virus particles bearing FeLV-945 SU bind to the FeLV-A receptor more efficiently than do particles bearing FeLV-A/61E SU, and that soluble SU proteins expressed from the viruses demonstrate the same differential binding phenotype. Preliminary mutational analysis of FeLV-945 was performed by exchanging regions containing either the primary receptor binding determinant, VRA, the secondary determinant, VRB, or a proline-rich region, PRR, with that of FeLV-A/61E. Results implicated a region containing VRA as a minor contributor, while a region containing VRB largely conferred increased binding efficiency. Copyright © 2011 Elsevier B.V. All rights reserved.
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Left ventricular mass in elite olympic weight lifters.
Lalande, Sophie; Baldi, James Christopher
2007-10-01
The existence of resistance training-induced left ventricular (LV) concentric hypertrophy is equivocal. Although some have described significant LV hypertrophy, others have suggested that training-induced LV hypertrophy is proportional to increased fat free mass (FFM) and thus a normal physiologic response to training. Method limitations, steroid use, and type of training may contribute to discrepant findings. Thus, LV structure and volumes are determined using magnetic resonance imaging. Body composition was determined using dual-energy x-ray absorptiometry in 9 elite Olympic weight lifters and 10 age- and weight-matched recreationally active controls. LV structure and volumes were determined by acquiring 6 short- and 3 long-axis magnetic resonance imaging scans of the left ventricle, whereas LV wall thickness was defined as the average of 6 midventricular segment thickness measurements. Weight lifters had the same age, weight, and FFM, but were shorter and had a greater body mass index than controls. LV mass was not different in weight lifters and controls, but was lower in weight lifters when indexed to FFM (2.56 +/- 0.07 vs 2.30 +/- 0.05, p = 0.01). LV mass correlated with FFM (r = 0.49, p = 0.04). However, LV mass was lower in weight lifters for a given FFM. LV wall thickness, as well as end-diastolic, end-systolic, and stroke volumes, were not different between groups. In conclusion, these results refute the hypothesis that resistance training induces LV concentric hypertrophy and suggest that Olympic weight lifting is associated with increases in FFM without a concomitant increase in LV mass.
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NASA Technical Reports Server (NTRS)
Radharkrishnan, Krishnan; Kaiser, Peter K.
2011-01-01
By both fractal (D1) and branching (Lv) analysis, macular arterial density oscillated with progression from mild NPDR to PDR. Results are consistent with out study reported recently for the entire arterial and venous branching trees within 50 degree FAs by VESGEN generational branching analysis. Current and previous results are important for advances in early-stage regenerative DR therapies, for which reversal of DR progression to a normal vessel density may be possible. For example, potential use of regenerative angiogenesis stimulators to reverse vascular dropout during mild and severe NPDR is not indicated for treatment of moderate NPDR.
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Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F; Salton, Carol J; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J
2014-04-01
To determine sex-specific reference values for left ventricular (LV) volumes, mass, and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. We examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses, we stratified participants by age-decade and tested for linear trend across age groups. The reference group comprised 685 adults (423F; 61 ± 9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all P = 0.001). Women had greater EF (73 ± 6 versus 71 ± 6%; P = 0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. We present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF, and geometry, whereas mass differs between sexes but not age groups. Copyright © 2013 Wiley Periodicals, Inc.
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Chuang, Michael L.; Gona, Philimon; Hautvast, Gilion L.T.F.; Salton, Carol J.; Breeuwer, Marcel; O’Donnell, Christopher J.; Manning, Warren J.
2013-01-01
Purpose To determine sex-specific reference values for left ventricular (LV) volumes, mass and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. Methods and Methods We examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses we stratified participants by age-decade and tested for linear trend across age groups. Results The reference group comprised 685 adults (423F; 61±9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all p<0.001). Women had greater EF (73±6 vs. 71±6%, p=0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. Conclusion We present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF and geometry, while mass differs between sexes but not age groups. PMID:24123369
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Foxe, David; Leyton, Cristian E; Hodges, John R; Burrell, James R; Irish, Muireann; Piguet, Olivier
2016-10-01
Logopenic progressive aphasia (lv-PPA) is a form of primary progressive aphasia and is predominantly associated with Alzheimer's disease (AD) pathology. The neuropsychological profiles of lv-PPA and typical clinical AD are, however, distinct. In particular, these two syndromes differ on attention span measures, where auditory attention span is more impaired in lv-PPA than in AD and visuospatial span appears more impaired in AD than in lv-PPA. The neural basis of these span profiles, however, remains unclear. Sixteen lv-PPA and 21 AD matched patients, and 15 education-matched healthy controls were recruited. All participants were assessed by a neurologist and completed a neuropsychological assessment that included the Wechsler Memory Scale-III Digit and Spatial Span tasks, and underwent a high-resolution structural brain MRI to conduct cortical thickness analyses. Patient groups were impaired on all span tasks compared to Controls. In addition, performance on Digit Span Forward (DSF) was significantly lower in the lv-PPA than the AD group, while Spatial Span Forward (SSF) was significantly lower in the AD than the lv-PPA group. No differences were found between patient groups on the Digit or Spatial Span Backward tasks. Neuroimaging analyses revealed that reduced DSF performance correlated to thinning of the left superior temporal gyrus in the lv-PPA group, whereas reduced SSF performance was related to bilateral precentral sulcus and parieto-occipital thinning in the AD group. Analyses of the backward span tasks revealed that reduced Spatial Span Backward (SSB) performance in the lv-PPA group related to cortical thinning of the left superior parietal lobule. This study demonstrates that while lv-PPA and AD commonly share the same underlying neuropathology, their span profiles are distinct and are mediated by divergent patterns of cortical degeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Maiello, Maria; Zito, Annapaola; Carbonara, Santa; Ciccone, Marco Matteo; Palmiero, Pasquale
2017-10-01
Coronary artery disease (CAD) is quite common among diabetic patients, our study goal is to detect the prevalence of left ventricular (LV) adverse changes in geometry, mass and diastolic function on diabetic, but not hypertensive patients, with coronary artery disease(CAD) and LV ejection fraction(LVEF)>45%, actually unknown, because of current guidelines that do not include echocardiographic assessment for follow up of diabetic patients. 665 consecutive diabetic patients (443 females, mean age 66±9years), performed a complete echocardiographic assessment according to current ASE echo-guidelines: diastolic dysfunction (DD), eccentric hypertrophy (EH), concentric hypertrophy (CH) and concentric remodeling (CR) of LV were reported. CAD was assessed only by reports of bypass surgery, angioplasty or patients hospitalized for acute myocardial infarction. 218 patients (32.8%) presented LV changes: LVDD 49 (7.4%), LVEH 68 (10.2%), LVDD and EH 46 (6.9%), LVDD and CH 36 (5.4%), LVDD and CR 19 (2.9%). 447 (67.2%) had no LV changes. 81 (12.1%) patients with CAD, presented: LVDD 17 (21%), LVEH 32 (39.5%), LVDD and EH 9 (11.1%), LVDD and CH 7 (8.6%), LVDD and CR 8 (9.9%), 8 (9.9%) had no LV adverse changes. There were among CAD patients, a significantly higher prevalence of LVDD (p<0.02), LV eccentric hypertrophy (EH) (p<0.05), DD and LVEH (p<0.04), DD and LV concentric hypertrophy(CH) (p<0.03) and DD and LV concentric remodeling (p<0.02), when compared with those patients without CAD. CAD is related to all different patterns of LV adverse changes in mass, geometry and diastolic function, with a significantly higher prevalence in our population of diabetic patients with normal systolic function. These changes however remain unrecognized until they undergo to a conventional echocardiographic assessment. We support this tool need to be included into future guidelines concerning follow-up of diabetic patients. Copyright © 2017 Elsevier Inc. All rights reserved.
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Stabile, Giuseppe; Pepi, Patrizia; Palmisano, Pietro; D'Onofrio, Antonio; De Simone, Antonio; Caico, Salvatore Ivan; Pecora, Domenico; Rapacciuolo, Antonio; Arena, Giuseppe; Marini, Massimiliano; Pieragnoli, Paolo; Badolati, Sandra; Savarese, Gianluca; Maglia, Gianpiero; Iuliano, Assunta; Botto, Giovanni Luca; Malacrida, Maurizio; Bertaglia, Emanuele
2018-04-14
Professional guidelines are based on the best available evidence. However, patients treated in clinical practice may differ from those included in reference trials. The aim of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in a large population of patients implanted with a CRT device stratified in accordance with the 2016 European heart failure (HF) guidelines. We collected data on 930 consecutive patients from the Cardiac Resynchronization Therapy MOdular REgistry. The primary end point was a composite of death and HF hospitalization. Five hundred sixty-three (60.5%) patients met class I indications, 145 (15.6%) class IIa, 108 (11.6%) class IIb, and 114 (12.3%) class III. After a median follow-up of 1001 days, 120 patients who had an indication for CRT implantation had died and 71 had been hospitalized for HF. The time to the end point was longer in patients with a class I indication (hazard ratio 0.55; 95% confidence interval 0.39-0.76; P = .0001). After 12 months, left ventricular (LV) end-systolic volume had decreased by ≥15% in 61.5% of patients whereas in 57.5% of patients the absolute LV ejection fraction improvement was ≥5%. Adherence to class I was also associated with an absolute LV ejection fraction increase of >5% (P = .0142) and an LV end-systolic volume decrease of ≥15% (P = .0055). In our population, ∼60% of patients underwent implantation according to the 2016 European HF guidelines class I indication. Adherence to class I was associated with a lower death and HF hospitalization rate and better LV reverse remodeling. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
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Abidov, A; Hachamovitch, R; Berman, D S
2004-12-01
Congestive heart failure (CHF) has become a large social burden in modern Western society, with very high morbidity and mortality and extremely large financial costs. The largest cause of CHF is coronary heart disease, with ventricular dysfunction that may or may not be reversible by revascularization. Thus, evaluation of the viable myocardial tissue in patients with ischemic left ventricular (LV) dysfunction has important clinical and therapeutic implications. Furthermore, since patients with ventricular dysfunction are at higher operative risk, cardiologists and cardiac surgeons are commonly faced with issues regarding the balance between the potential risk vs benefit of revascularization procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and positron emission tomography (PET)] provide objective information that augments standard clinical and angiographic assessments of patients with ventricular dysfunction with respect to diagnosis (etiology), prognosis, and potential benefit from intervention. Development of the technology and methodology of gated MPS, now the routine method for MPS, allows assessment of the extent and severity of inducible ischemia as well as hypoperfused but viable myocardium, and also provides measurements of LV ejection fraction, regional wall motion, LV volume measurements, diastolic function and LV geometry. With PET, myocardial metabolism and blood flow reserve can be added to the measurements provided by nuclear cardiology procedures. This paper provides insight into the current evidence regarding settings in which nuclear cardiac imaging procedures are helpful in assessment of patients in the setting of coronary artery disease with severe LV dysfunction. A risk-benefit approach to MPS results is proposed, with principal focus on identifying patients at risk for major cardiac events who may benefit from myocardial revascularization.
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NASA Technical Reports Server (NTRS)
Sitges, Marta; Shiota, Takahiro; Lever, Harry M.; Qin, Jian Xin; Bauer, Fabrice; Drinko, Jeannie K.; Agler, Deborah A.; Martin, Maureen G.; Greenberg, Neil L.; Smedira, Nicholas G.;
2003-01-01
Both percutaneous transcoronary alcohol septal reduction (ASR) and surgical myectomy are effective treatments to relieve left ventricular (LV) outflow tract obstruction in obstructive hypertrophic cardiomyopathy (HC). LV diastolic function was assessed by echocardiography in 57 patients with obstructive HC at baseline and 5 +/- 4 months after ASR (n = 37) or surgical myectomy (n = 20). LV outflow tract pressure gradient decreased from 65 +/- 40 to 23 +/- 21 mm Hg (p <0.01) after treatment. The ratio of the early-to-late peak diastolic LV inflow velocities, and the ratio of the early peak diastolic LV inflow velocity to the lateral mitral annulus early diastolic velocity determined by tissue Doppler imaging significantly decreased after the procedures (1.6 +/- 1.7 vs 1.0 +/- 0.7 and 15 +/- 8 vs 11 +/- 5, respectively), whereas LV inflow propagation velocity significantly increased (60 +/- 24 vs 71 +/- 36 cm/s). Left atrial size decreased from 29 +/- 7 to 25 +/- 6 cm(2) (p <0.05). Patients had a significant improvement in New York Heart Association functional class and in exercise performance. When comparing ASR with myectomy, no difference was found in the degree of change in any parameter of diastolic function. Thus, diastolic function indexes obtained by echocardiography changed after septal reduction interventions in patients with obstructive HC; this change was similar to that after surgical myectomy and ASR.
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Duong, Le T; Crawford, Randy; Scott, Kevin; Winkelmann, Christopher T; Wu, Gouxin; Szczerba, Pete; Gentile, Michael A
2016-12-01
Odanacatib (ODN) a selective and reversible cathepsin K inhibitor, inhibits bone resorption, increases bone mass and reduces fracture risk in women with osteoporosis. A 16-month (~7-remodeling cycles) study was carried out in treatment mode to assess the effects of ODN versus ALN on bone mass, remodeling status and biomechanical properties of lumbar vertebrae (LV) and femur in ovariectomized (OVX) rabbits. This study also evaluated the impact of discontinuing ODN on these parameters. Rabbits at 7.5months post-OVX were dosed for 16-months with ODN (7.5μM·h 0-24 , in food) or ALN (0.2mg/kg/wk, s.c.) and compared to vehicle-treated OVX- (OVX+Veh) or Sham-operated animals. After 8months, treatment was discontinued in half of the ODN group. ODN treatment increased in vivo LV aBMD and trabecular (Tb) vBMD until reaching plateau at month 12 by 16% and 23% vs. baseline, respectively, comparable levels to that in Sham and significantly above OVX+Veh. LV BMD was also higher in ALN that plateaued around month 8 to levels below that in ODN or Sham. ODN treatment resulted in higher BMD, structure and improved biomechanical strength of LV and central femur (CF) to levels similar to Sham. ALN generally showed less robust efficacy compared to ODN. Neither ODN nor ALN influenced material properties at these bone sites following ODN or ALN treatment for 7 remodeling cycles in rabbits. ODN and ALN persistently reduced the bone resorption marker urinary helical peptide over study duration. While ALN reduced the bone formation marker BSAP, ODN treatment did not affect this marker. ODN also preserved histomorphometry-based bone formation indices in LV trabecular, CF endocortical and intracortical surfaces, at the levels of OVX+Veh. Discontinuation of ODN returned bone mass, structure and strength parameters to the comparable respective levels in OVX+Veh. Together, these data demonstrate efficacy and bone safety profile of ODN and suggests the potential long-term benefits of this agent over ALN with respect to accrued bone mass without long-term effects on bone formation. Copyright © 2016 Elsevier Inc. All rights reserved.
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Huang, Chun-kai; Chen, Bi-yi; Guo, Ang; Chen, Rong; Zhu, Yan-qi; Kutschke, William; Hong, Jiang; Song, Long-sheng
2016-01-01
Aim: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits. Methods: A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg·kg−1·d−1, sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results: TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R2=0.74, P<0.01) and global LV function (R2=0.47, P<0.01). Conclusion: Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure. PMID:26972492
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Ehara, Shoichi; Okuyama, Takuhiro; Shirai, Nobuyuki; Sugioka, Kenichi; Oe, Hiroki; Itoh, Toshihide; Matsuoka, Toshiyuki; Ikura, Yoshihiro; Ueda, Makiko; Naruko, Takahiko; Hozumi, Takeshi; Yoshiyama, Minoru
2009-08-01
Previous studies have shown a correlation between coronary artery cross-sectional diameter and left ventricular (LV) mass. However, no studies have examined the correlation between actual coronary artery volume (CAV) and LV mass. In the present study, measurements of CAV by 64-multislice computed tomography (MSCT) were validated and the relationship between CAV and LV mass was investigated. First, coronary artery phantoms consisting of syringes filled with solutions of contrast medium moving at simulated heart rates were scanned by 64-MSCT. Display window settings permitting accurate calculation of small volumes were optimized by evaluating volume-rendered images of the segmented contrast medium at different window settings. Next, 61 patients without significant coronary artery stenosis were scanned by 64-MSCT with the same protocol as for the phantoms. Coronary arteries were segmented on a workstation and the same window settings were applied to the volume-rendered images to calculate total CAV. Significant correlations between total CAV and LV mass (r=0.660, P<0.0001) were found, whereas an inverse relation was present between total CAV per 100 g of LV mass and LV mass. The novel concept of "CAV" for the characterization of coronary arteries may prove useful for future research, particularly on the causes of LV hypertrophy.
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Gürbak, İsmail; Yıldız, İbrahim; Panç, Cafer
2018-01-29
The assessment of left ventricular (LV) structure and function is important in the evaluation of hypertensive heart disease, as it provides information on the cardiovascular morbidity and mortality. Aortic knob width (AKW) is a measurement of radiographic structure formed by the foreshortened aortic arch and a portion of the descending aorta. The main aim of this study was to investigate the relation between AKW on the routine chest radiography and subclinical LV dysfunction in hypertensive patients. A total of 144 patients with hypertension admitted to the cardiology outpatients clinic were enrolled consecutively. The patients were divided into two groups according to tissue Doppler-derived myocardial performance index (MPI): subclinical LV dysfunction group (abnormal MPI ≥ 0.5, n = 85) and absence of subclinical LV dysfunction group (normal MPI< 0.5, n = 59). Patients with subclinical LV dysfunction were older (60 ± 8 vs. 54 ± 8, p = 0.001). Left ventricular mass index (LVMI) (96 ± 27 vs. 74 ± 24, p < 0.001) and prevalence of LV hypertrophy (28 vs. 8%, p = 0.011) were significantly different between two groups. Patients with subclinical LV dysfunction had higher AKW (42 ± 6 vs. 34 ± 5, p < 0.001) compared with patients without subclinical LV dysfunction. There was a significant correlation between MPI and AKW (r = 0.7, p < 0.001). Multiple logistic regression analysis showed that AKW (β = 0.617, p = 0.001) and posterior wall thickness (PWth) (β = 1.189, p = 0.021) were independently associated with subclinical LV dysfunction. Analysis using the Receiver Operating Characteristic (ROC) curve has demonstrated that aortic knob of 37 mm constitutes the cutoff value for the presence of subclinical LV dysfunction with 85.9% sensitivity and 86.4% specificity (The Area under the Curve ± Standard Error (AUC±SE) = 0.916 ± 0.024, p < 0.001). AKW may provide important predictive information on subclinical LV dysfunction in patients with hypertension.
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2014-01-01
Background Although increased volume of pericardial fat has been associated with decreased cardiac function, it is unclear whether this association is mediated by systemic overall obesity or direct regional fat interactions. We hypothesized that if local effects dominate, left ventricular (LV) function would be most strongly associated with pericardial fat that surrounds the left rather than the right ventricle (RV). Methods Female obese subjects (n = 60) had cardiovascular magnetic resonance (CMR) scans to obtain measures of LV function and pericardial fat volumes. LV function was obtained using the cine steady state free precession imaging in short axis orientation. The amount of pericardial fat was determined volumetrically by the cardiac gated T1 black blood imaging and normalized to body surface area. Results In this study cohort, LV fat correlated with several LV hemodynamic measurements including cardiac output (r = -0.41, p = 0.001) and stroke volume (r = -0.26, p = 0.05), as well as diastolic functional parameters including peak-early-filling rate (r = -0.38, p = 0.01), early late filling ratio (r = -0.34, p = 0.03), and time to peak-early-filling (r = 0.34, p = 0.03). These correlations remained significant even after adjusting for the body mass index and the blood pressure. However, similar correlations became weakened or even disappeared between RV fat and LV function. LV function was not correlated with systemic plasma factors, such as C-reactive protein (CRP), B-type natriuretic peptide (BNP), Interleukin-6 (IL-6), resistin and adiponectin (all p > 0.05). Conclusions LV hemodynamic and diastolic function was associated more with LV fat as compared to RV or total pericardial fat, but not with systemic inflammatory markers or adipokines. The correlations between LV function and pericardial fat remained significant even after adjusting for systemic factors. These findings suggest a site-specific influence of pericardial fat on LV function, which could imply local secretion of molecules into the underlying tissue or an anatomic effect, both mechanisms meriting future evaluation. PMID:24884541
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Bande, Faruku; Arshad, Siti Suri; Hassan, Latiffah; Zakaria, Zunita; Sapian, Nurul Asyikin; Rahman, Noor Alimah; Alazawy, Amer
2012-03-22
Feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) are major causes of morbidity and mortality in domestic and wild felids. Despite the clinical importance of feline retroviruses and the growing interest in cats as pets, information about FeLV and FIV in Malaysia is presently insufficient to properly advise veterinarians and pet owners. A cross-sectional study was carried out from January 2010 to December 2010 to determine the prevalence and risk factors associated with FeLV and FIV among domestic cats in peninsular Malaysia. Plasma samples were harvested from the blood of 368 domestic cats and screened for evidence of FeLV p27 antigen and FIV antibodies, using an immunochromatographic kit. Additionally, data on cat demographics and health were collected using a structured questionnaire, and were evaluated as potential risk factors for FeLV or FIV status. Of the 368 cats that were evaluated in this study, 12.2% (45/368; 95% CI = 8.88 - 15.58) were positive for FeLV p27 antigen, 31.3%, (115/368; 95% CI = 26.51 - 35.99) were seropositive to FIV antibodies, and 4.3% (16/368; 95% CI = 2.27 - 6.43) had evidence of both viruses. Factors found to significantly increase the risk for FeLV seropositivity include sex, age, behaviour, sickness, and living in a multi-cat household. Seropositive response to FIV was significantly associated with sex, neuter status, age, behaviour, and health status. The present study indicates that FeLV and FIV are common among domestic cats in peninsular Malaysia, and that factors related to cat demographics and health such as age, sex, behaviour, health status and type of household are important predictors for seropositive status to FeLV or FIV in peninsular Malaysia. High prevalence of FeLV or FIV observed in our study is of concern, in view of the immunosuppressive potentials of the two pathogens. Specific measures for control and prevention such as screening and routine vaccination are needed to ensure that FeLV and FIV are controlled in the cat population of peninsular Malaysia.
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Hong, Sung-Jin; Shim, Chi Young; Kim, Darae; Cho, In-Jeong; Hong, Geu-Ru; Moon, Sun-Ha; Lee, Hyun-Jin; Lee, Jin-Kyung; Choi, Donghoon; Jang, Yangsoo; Ha, Jong-Won
2018-01-01
We hypothesized that the absence of a decrease in minimal left ventricular (LV) pressure during exercise would be associated with impaired LV apical back rotation during exercise. A total of 21 patients (59 ± 10 years) underwent invasive LV pressure measurements and simultaneous echocardiography at rest and during submaximal supine bicycle exercise. Patients were classified according to the changes in minimal LV pressure from rest to maximal exercise (Δminimal LVP); Group 1 (n = 8) had a decrease in minimal LV pressure with exercise, whereas Group 2 (n = 13) had an increase in minimal LV pressure. LV apical back-rotation parameters by speckle-tracking echocardiography at rest and during 50 W of exercise were compared. At rest, there were no differences in LV pressure and echocardiographic parameters between groups. However, at 50 W of exercise, Group 2 had higher LV early and end-diastolic pressures and a prolonged time constant of LV relaxation. In Group 2, e' velocity was lower and E/e' was higher. Apical back rotation at the mitral valve opening (MVO) was reduced and minimal apical back-rotation velocity was lower in Group 2. Δminimal LVP significantly correlated with apical back rotation at MVO (r = -0.77, P = 0.009) and minimal apical back-rotation velocity at 50 W (r = 0.69, P = 0.028). The lack of decrease in minimal LV pressure during exercise, a manifestation of impaired LV suction in early diastole, is linked closely with impaired LV apical back rotation during exercise. Dynamic changes in LV apical back rotation during exercise can be used as a non-invasive parameter of diastolic suction during exercise. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
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Ikeo, T; Nagao, T
1985-10-01
We compared the effects of denopamine (TA-064) and isoproterenol on hemodynamics, myocardial oxygen consumption and the left ventricular (LV) dimension in halothane-N2O anesthetized dogs. Denopamine (0.25-1 micrograms/kg/min, i.v., infusion X 15 min) produced a maximum increase in LV dp/dtmax by 64% of the control, without affecting aortic pressure significantly. Doses of isoproterenol (0.01-0.04 micrograms/kg/min, i.v., infusion X 15 min) were selected to produce a positive inotropic action similar to that of denopamine. Denopamine produced significantly less increasing effects in heart rate, cardiac output and myocardial oxygen consumption and had more reducing effects in LV internal diameter than isoproterenol, while isoproterenol tended to produce a more potent increase in coronary blood flow, but a smaller decrease in LV end-diastolic pressure than denopamine. PQ interval was similarly reduced. Denopamine caused no substantial increase in myocardial oxygen consumption at a lower dose, at which LV dp/dtmax was significantly increased. A weak effect of denopamine on myocardial oxygen consumption may result partly from a weak positive chronotropic effect and partly from a reduction of preload and cardiac size.
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NASA Technical Reports Server (NTRS)
Tabata, T.; Oki, T.; Yamada, H.; Abe, M.; Onose, Y.; Thomas, J. D.
2000-01-01
BACKGROUND: Tissue Doppler imaging (TDI) is a recently developed technique that allows the instantaneous measurement of intrinsic regional myocardial motion velocity. Pulsed TDI is capable of separately assessing left ventricular (LV) regional motion velocity caused by circumferential and longitudinal fiber contraction. This particular feature of function is still controversial in patients with hypertrophic cardiomyopathy (HC). METHODS: To better characterize intrinsic circumferential and longitudinal LV systolic myocardial function in HC, we used pulsed TDI to measure short- and long-axis LV motion velocities, respectively. The subendocardial motion velocity patterns at the middle of the LV posterior wall (PW) and ventricular septum (IVS) in LV parasternal and apical long-axis views were recorded by pulsed TDI in 19 patients with nonobstructive HC and in 21 normal controls (NC). RESULTS: Peak short- and long-axis systolic subendocardial velocities in both the LV PW and IVS were significantly smaller in the HC group than in the NC group, and the time to peak velocity was significantly delayed. Furthermore, peak PW systolic velocity was significantly greater along the long axis than along the short axis in the NC group (8.8 +/- 1.5 cm/s vs 8.2 +/- 1.4 cm/s, P <.05), whereas the opposite was observed in the HC group (6.1 +/- 1.2 cm/s vs 7.5 +/- 1.0 cm/s, P <.0001). No significant differences were found in either group between the long- and short-axis IVS velocities (HC: 5.9 +/- 1.4 cm/s vs 5.5 +/- 1.3 cm/s; NC: 7.8 +/- 1.3 cm/s vs 7.9 +/- 1.6 cm/s). CONCLUSIONS: By using the capability of pulsed TDI for the evaluation of intrinsic myocardial velocity instantaneously in a specific region and direction, we found impairment of LV myocardial systolic function in patients with HC not only in the hypertrophied IVS but also in the nonhypertrophied LV PW. We also found a greater decrease in LV PW velocities along the long axis than the short axis, suggesting greater impairment of long-axis contraction in patients with HC. Because our HC patients did not appear to have excessive intracavitary pressure, these results suggest that the relatively normal-appearing PW is directly affected by the HC pathologic process.
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DNA electrotransfer into the skin using a combination of one high- and one low-voltage pulse.
Pavselj, N; Préat, V
2005-09-02
Electroporation is an effective alternative to viral methods to significantly improve DNA transfection after intradermal and topical delivery. The aim of the study was to check whether a combination of a short high-voltage pulse (HV) to permeabilize the skin cells and a long low-voltage pulse (LV) to transfer DNA by electrophoresis was more efficient to enhance DNA expression than conventional repeated HV or LV pulses alone after intradermal injection of DNA plasmid. GFP and luciferase expressions in the skin were enhanced by HV+LV protocol as compared to HV or LV pulses alone. The expression lasted for up to 10 days. Consistently, HV+LV protocol induced a higher Th2 immune response against ovalbumin than HV or LV pulses. Standard methods were used to assess the effect of electric pulses on skin: the application of a combination of HV and LV pulses on rat skin fold delivered by plate electrodes was well tolerated. These data demonstrate that a combination of one HV (700 to 1000 V/cm; 100 micros) followed by one LV (140 to 200 V/cm; 400 ms) is an efficient electroporation protocol to enhance DNA expression in the skin.
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Systolic Intrinsic Frequency and Various Measures of Left Ventricle Contractility
NASA Astrophysics Data System (ADS)
Pahlevan, Niema
2017-11-01
There has been growing interest during past six decades to introduce new indices for quantifying left ventricular (LV) contractility. We have recently introduced a new method, called intrinsic frequency (IF), for analyzing the dynamics of systemic circulation. IF method models LV and arterial network as an object rotating around an origin where the angular velocity of the rotation during systole (when LV and arterial network are coupled) and diastole (when arterial network is decoupled) are intrinsic frequencies, ω1 and ω2 respectively. ω1 and ω2 can be extracted from a carotid pulse waveform using IF method. In this study, Huntington Medical Research Institutes heart study data have been used to compare ω1 with various measures of LV contractility such as ejection fraction, mean velocity of circumferential fiber shortening, LV end-systolic meridional wall stress, and maximal LV power corrected for end-diastolic volume. Here, LV contractility indices were computed noninvasively from cardiac MRI and tonometry data. The results indicate that ω1 can be used as a surrogate of LV contractility. This is clinically significant since ω1 can be accurately obtained by a standard iPhone camera.
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Beneficial role of tamoxifen in isoproterenol-induced myocardial infarction.
Rayabarapu, Nihar; Patel, Bhoomika M
2014-10-01
ER-α and ER-β agonist 17β-estradiol is reported to attenuate cardiac hypertrophy. Tamoxifen is a selective estrogen receptor modulator. Hence, the objective of this study was to investigate the effects of tamoxifen in myocardial infarction. For this, tamoxifen was administered to Sprague-Dawley rats for 1-14 days, and isoproterenol (ISO) (100 mg·(kg body mass)(-1)·day(-1)) was administered subcutaneously on the 13th and 14th days of the study in order to induce myocardial infarction, after which, various biochemical, cardiac, and morphometric parameters were evaluated. ISO produced significant dyslipidemia, hypertension, bradycardia, oxidative stress, and an increase in serum cardiac markers. Treatment with tamoxifen significantly controlled dyslipidemia, hypertension, bradycardia, oxidative stress, and reduced serum cardiac markers. The ISO control rats exhibited significant increases in the infarct size of the left ventricle (LV), LV cavity area, cardiac and LV hypertrophic indices, LV-wall thickness, cardiomyocyte diameter, and area. Treatment with tamoxifen significantly reduced infarction as well as hypertrophic and morphometric parameters. ISO also produced significant increases in the LV collagen level, decreases in Na(+)K(+) ATPase activity, and a reduction in the rate of pressure development and decay, which were prevented by tamoxifen treatment. The protective effect of tamoxifen on myocardial infarct was further confirmed by histopathological examination. Our data thus suggest that tamoxifen exerts beneficial effects in ISO-induced myocardial infarction.
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Zhao, Ying-Zheng; Tian, Xin-Qiao; Zhang, Ming; Cai, Lu; Ru, Ao; Shen, Xiao-Tong; Jiang, Xi; Jin, Rong-Rong; Zheng, Lei; Hawkins, Kyle; Charkrabarti, Subrata; Li, Xiao-Kun; Lin, Qian; Yu, Wen-Ze; Ge, Shuping; Lu, Cui-Tao; Wong, Ho Lun
2014-07-28
Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats. bFGF-loaded NP (bFGF-NP) were prepared with Poloxamer 188-grafted heparin copolymer using water-in-water technique, and the morphology, encapsulation efficiency, and bioactivity of bFGF-NP were studied. The cellular uptake and cytotoxicity of bFGF-NP were evaluated with primary cultures of the left ventricular (LV) cardiomyocytes in vitro. Therapeutic effects of bFGF-NP/UTMD on the heart of DCM rats were studied by measuring LV systolic and diastolic functions, hemodynamic characteristics and indicators of cardiac remodeling including myocardial collagen volume fraction and capillary density. Results demonstrated that bFGF-NP showed good round morphology, efficient bFGF encapsulation and stable bioactivity of bFGF in vitro. bFGF-NP/UTMD combined treatment significantly enhanced the efficiency of bFGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements (P<0.05) in both cardiac functions and tissue morphology in the DCM rats were observed in bFGF-NP/UTMD group. These were not achievable using free bFGF, bFGF-NP or UTMD treatment alone. Our results show that combining a non-viral vector with UTMD technique is an effective strategy to deliver bFGF to the heart, and the resulting growth factor therapy has demonstrated potential to reverse the progress of DCM by restoring the cardiac functions and even the structure of damaged cardiac tissues. Copyright © 2014 Elsevier B.V. All rights reserved.
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NASA Technical Reports Server (NTRS)
Qin, J. X.; Jones, M.; Shiota, T.; Greenberg, N. L.; Tsujino, H.; Firstenberg, M. S.; Gupta, P. C.; Zetts, A. D.; Xu, Y.; Ping Sun, J.;
2000-01-01
OBJECTIVES: To validate the accuracy of real-time three-dimensional echocardiography (RT3DE) for quantifying aneurysmal left ventricular (LV) volumes. BACKGROUND: Conventional two-dimensional echocardiography (2DE) has limitations when applied for quantification of LV volumes in patients with LV aneurysms. METHODS: Seven aneurysmal balloons, 15 sheep (5 with chronic LV aneurysms and 10 without LV aneurysms) during 60 different hemodynamic conditions and 29 patients (13 with chronic LV aneurysms and 16 with normal LV) underwent RT3DE and 2DE. Electromagnetic flow meters and magnetic resonance imaging (MRI) served as reference standards in the animals and in the patients, respectively. Rotated apical six-plane method with multiplanar Simpson's rule and apical biplane Simpson's rule were used to determine LV volumes by RT3DE and 2DE, respectively. RESULTS: Both RT3DE and 2DE correlated well with actual volumes for aneurysmal balloons. However, a significantly smaller mean difference (MD) was found between RT3DE and actual volumes (-7 ml for RT3DE vs. 22 ml for 2DE, p = 0.0002). Excellent correlation and agreement between RT3DE and electromagnetic flow meters for LV stroke volumes for animals with aneurysms were observed, while 2DE showed lesser correlation and agreement (r = 0.97, MD = -1.0 ml vs. r = 0.76, MD = 4.4 ml). In patients with LV aneurysms, better correlation and agreement between RT3DE and MRI for LV volumes were obtained (r = 0.99, MD = -28 ml) than between 2DE and MRI (r = 0.91, MD = -49 ml). CONCLUSIONS: For geometrically asymmetric LVs associated with ventricular aneurysms, RT3DE can accurately quantify LV volumes.
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Cosyns, Bernard; Droogmans, Steven; Weytjens, Caroline; Lahoutte, Tony; Van Camp, Guy; Schoors, Danny; Franken, Philippe R
2007-01-01
Background Recent studies have suggested that diabetes mellitus (DM) may cause left ventricular (LV) dysfunction directly resulting in increased susceptibility to heart failure. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The present study was aimed to assess this new imaging technique for quantifying LV function and remodeling from the Streptozotocin (STZ) rat model compared to controls. Methods Twenty one rats were randomly assigned to control or diabetic group. Six months after the induction of diabetes by STZ, Pinhole 99 m Tc-sestamibi gated SPECT was performed for determining rat LV volumes and function. Post-mortem histopathologic analysis was performed to evaluate the determinant of LV remodeling in this model. Results After six months, the normalized to body weight LV End-systolic volume was significantly different in diabetic rats compared to controls (0.46 ± 0.02 vs 0.33 ± 0.03 μL/g; p = 0.01). The normalized LV End-diastolic volume was also different in both groups (1.51 ± 0.03 vs 0.88 ± 0.05 μL/g; p = 0.001) and the normalized stroke volume was significantly higher in STZ-rats (1.05 ± 0.02 vs 0.54 ± 0.06 μL/g; p = 0.001). The muscular fibers were thinner at histology in the diabetic rats (0.44 ± 0.07 vs 0.32 ± 0.06 AU; p = 0.01). Conclusion Pinhole 99 m Tc-sestamibi gated SPECT can successfully be applied for the evaluation of cardiac function and remodeling in STZ-induced diabetic rats. In this model, LV volumes were significantly changed compared to a control population, leading to a LV dysfunction. These findings were consistent with the histopathological abnormalities. Finally, these data further suggest the presence of diabetes cardiomyopathy. PMID:17937784
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Larghat, Abdulghani M; Swoboda, Peter P; Biglands, John D; Kearney, Mark T; Greenwood, John P; Plein, Sven
2014-12-01
Type 2 diabetes mellitus is an independent risk factor for the development of heart failure. To better understand the mechanism by which this occurs, we investigated cardiac structure, function, and perfusion in patients with and without diabetes. Sixty-five patients with no stenosis >30% on invasive coronary angiography were categorized into diabetes (19) and non-diabetes (46) which was further categorized into prediabetes (30) and controls (16) according to the American Diabetes Association guidelines. Each patient underwent comprehensive cardiovascular magnetic resonance assessment. Left-ventricular (LV) mass, relative wall mass (RWM), Lagrangian circumferential strain, LV torsion, and myocardial perfusion reserve (MPR) were calculated. LV mass was higher in diabetics than non-diabetics (112.8 ± 39.7 vs. 91.5 ± 21.3 g, P = 0.01) and in diabetics than prediabetics (112.8 ± 39.7 vs. 90.3 ± 18.7 g, P = 0.02). LV torsion angle was higher in diabetics than non-diabetics (9.65 ± 1.90 vs. 8.59 ± 1.91°, P = 0.047), and MPR was lower in diabetics than non-diabetics (2.10 ± 0.76 vs. 2.84 ± 1.25 mL/g/min, P = 0.01). There was significant correlation between MPR and early diastolic strain rate (r = -0.310, P = 0.01) and LV torsion (r = -0.306, P = 0.01). In multivariable linear regression analysis, non-diabetics waist-hip ratio, but not body mass index, had a significant association with RWM (Beta = 0.34, P = 0.02). Patients with diabetes have increased LV mass, LV torsion, and decreased MPR. There is a significant association between decreased MPR and increased LV torsion suggesting a possible mechanistic link between microvascular disease and cardiac dysfunction in diabetes. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Marui, Akira; Kimura, Takeshi; Nishiwaki, Noboru; Mitsudo, Kazuaki; Komiya, Tatsuhiko; Hanyu, Michiya; Shiomi, Hiroki; Tanaka, Shiro; Sakata, Ryuzo
2014-10-01
Coronary heart disease is a major risk factor for left ventricular (LV) systolic dysfunction. However, limited data are available regarding long-term benefits of percutaneous coronary intervention (PCI) in the era of drug-eluting stent or coronary artery bypass grafting (CABG) in patients with LV systolic dysfunction with severe coronary artery disease. We identified 3,584 patients with 3-vessel and/or left main disease of 15,939 patients undergoing first myocardial revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Of them, 2,676 patients had preserved LV systolic function, defined as an LV ejection fraction (LVEF) of >50% and 908 had impaired LV systolic function (LVEF≤50%). In patients with preserved LV function, 5-year outcomes were not different between PCI and CABG regarding propensity score-adjusted risk of all-cause and cardiac deaths. In contrast, in patients with impaired LV systolic function, the risks of all-cause and cardiac deaths after PCI were significantly greater than those after CABG (hazard ratio 1.49, 95% confidence interval 1.04 to 2.14, p=0.03 and hazard ratio 2.39, 95% confidence interval 1.43 to 3.98, p<0.01). In both patients with moderate (35%
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Alam, Mahboob; Zhang, Lily; Stampehl, Mark; Lakkis, Nasser; Dokainish, Hisham
2013-07-15
The acute impact of hypertensive crisis, and changes after treatment, on left ventricular (LV) systolic and diastolic function using comprehensive echocardiography, including speckle tracking, has not been well characterized. Thirty consecutive patients admitted to the hospital from the emergency room with hypertensive crisis underwent Doppler echocardiography at baseline and after blood pressure optimization. The mean age of the patients was 54 ± 13 years, with 19 men (63%). The most common presenting symptoms included dyspnea (70%), chest pain (43%), and altered mental status (13%). Mean systolic and diastolic blood pressures at presentation were 198 ± 12 and 122 ± 12 mm Hg, decreasing to 143 ± 15 and 77 ± 12 mm Hg (p <0.001 for both) after treatment. There was no significant change in LV ejection fraction between baseline and follow-up (48 ± 18% vs 46 ± 18%, p = 0.50); however, global longitudinal LV systolic strain (-10 ± 4% to -12 ± 4%, p = 0.01) and global systolic strain rate (-1.0 ± 0.4 vs -1.4 ± 0.6 s(-1), p = 0.01) significantly improved. Mean global early diastolic strain (-7.2 ± 4.0% to -9.4 ± 2.9%, p = 0.004) and early diastolic strain rate (0.3 ± 0.2 to 0.5 ± 0.4 s(-1), p = 0.05) also improved after treatment. On multivariate analysis, the independent predictors of LV longitudinal strain at follow-up were LV ejection fraction (p <0.001), heart rate (p = 0.005), systolic blood pressure (p = 0.04), and left atrial volume index (p = 0.05). In conclusion, as opposed to LV ejection fraction, LV systolic strain and strain rate were depressed during hypertensive crisis and significantly improved after medical treatment. LV diastolic function, assessed using conventional and speckle-tracking parameters, was also depressed and significantly improved after treatment. Copyright © 2013 Elsevier Inc. All rights reserved.
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Prevalence of feline leukaemia provirus DNA in feline lymphomas.
Weiss, Alexander Th A; Klopfleisch, Robert; Gruber, Achim D
2010-12-01
A significant drop in the prevalence of feline leukaemia virus (FeLV) antigenaemic cats and antigen-associated lymphomas has been observed after the introduction of FeLV vaccination and antigen-testing with removal of persistently antigenaemic cats. However, recent reports have indicated that regressively infected cats may contain FeLV provirus DNA and that lymphoma development may be associated with the presence of provirus alone. In the present study, we investigated the presence of FeLV antigen and provirus DNA in 50 lymphomas by immunohistochemistry and semi-nested polymerase chain reaction, respectively. Interestingly, almost 80% of T-cell lymphomas and 60% of B-cell lymphomas contained provirus DNA while only 21% of T-cell lymphomas and 11% of B-cell lymphomas expressed FeLV antigen. In conclusion, our results support previous hypotheses that vaccination and removal of persistently antigenaemic cats have led to a drop in FeLV antigen-expressing lymphomas. However, FeLV provirus DNA is still present in a high percentage of feline lymphomas. Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
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Chakkaramakkil Verghese, Santhosh; Goloviznina, Natalya A; Kurre, Peter
2016-11-19
Fanconi anemia (FA) is an autosomal-recessive disorder associated with hematopoietic failure and it is a candidate for hematopoietic stem cell (HSC)-directed gene therapy. However, the characteristically reduced HSC numbers found in FA patients, their ineffective mobilization from the marrow, and re-oxygenation damage during ex vivo manipulation have precluded clinical success using conventional in vitro approaches. We previously demonstrated that lentiviral vector (LV) particles reversibly attach to the cell surface where they gain protection from serum complement neutralization. We reasoned that cellular delivery of LV to the bone marrow niche could avoid detrimental losses during FA HSC mobilization and in vitro modification. Here, we demonstrate that a VSV-G pseudotyped lentivector, carrying the FANCC transgene, can be transmitted from carrier to bystander cells. In cell culture and transplantation models of FA, we further demonstrate that LV carrier cells migrate along SDF-1α gradients and transfer vector particles that stably integrate and phenotypically correct the characteristic DNA alkylator sensitivity in murine and human FA-deficient target bystander cells. Altogether, we demonstrate that cellular homing mechanisms can be harnessed for the functional phenotype correction in murine FA hematopoietic cells.
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Farag, El-Sayed M; Al-Daydamony, Mohammad M; Gad, Marwa M
2017-03-01
Heart failure (HF) is a major health problem. Hypertension is an important cause of HF. Most hypertensive patients have some degree of left ventricular (LV) diastolic dysfunction. The 6-minute walk test (6MWT) provides objective data about the exercise tolerance. We aimed to find the association between the degree of LV diastolic dysfunction and the functional capacity assessed by 6MWT in hypertensive patients. The study included 200 asymptomatic hypertensive patients. All patients had undergone full history taking, complete clinical examination, electrocardiography, echocardiography for assessment of LV dimensions, systolic and diastolic dysfunction, and 6MWT. Patients were classified into two groups according to the presence or absence of LV diastolic dysfunction. Clinical and echocardiographic data were comparable between the two groups. Regarding 6MWT, at the end of the test, patients with diastolic dysfunction had significantly higher systolic (P = .0088) and diastolic (P = .019) blood pressure and higher Borg score for dyspnea (P < .00001). The distant walked and percentage of the distance to predicted value were significantly lower in patients with diastolic dysfunction (P = .0322 and .0002, respectively). Incidence of abnormal 6MWT was significantly higher in patients with diastolic dysfunction (P = .00041). Compared to patients with grades I and II, patients with grade III diastolic dysfunction had significantly higher Borg score (P = .013), lower distance walked (P = .039), and lower percentage of distance to predicted vale (P = .009). Independent predictors for abnormal 6MWT were as follows: E/E' ≥15 (P = .0022), E'/A' <1 (P = .0081), and deceleration time of E-wave <160 (P = .013). The presence of LV diastolic dysfunction in hypertensive patients has a bad effect on 6MWT. The degree of LV diastolic dysfunction was correlated with 6MWT results. It may be important to investigate LV diastolic function in asymptomatic hypertensive patients. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
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Bunting, Ethan; Lambrakos, Litsa; Kemper, Paul; Whang, William; Garan, Hasan; Konofagou, Elisa
2016-01-01
Background Current electrocardiographic and echocardiographic measurements in heart failure (HF) do not take into account the complex interplay between electrical activation and local wall motion. The utilization of novel technologies to better characterize cardiac electromechanical behavior may lead to improved response rates with cardiac resynchronization therapy (CRT). Electromechanical Wave Imaging (EWI) is a non-invasive ultrasound-based technique that uses the transient deformations of the myocardium to track the intrinsic electromechanical wave that precedes myocardial contraction. In this paper, we investigate the performance and reproducibility of EWI in the assessment of HF patients and CRT. Methods EWI acquisitions were obtained in 5 healthy controls and 16 HF patients with and without CRT pacing. Responders (n=8) and non-responders (n=8) to CRT were identified retrospectively on the basis of left ventricular (LV) reverse remodeling. Electromechanical activation maps were obtained in all patients and used to compute a quantitative parameter describing the mean activation time of the LV lateral wall (LWAT). Results Mean LWAT was increased by 52.1 ms in HF patients in native rhythm compared to controls (p<0.01). For all HF patients, CRT pacing initiated a different electromechanical activation sequence. Responders exhibited a 56.4±28.9 ms reduction in LWAT with CRT pacing (p<0.01), while non-responders showed no significant change. Conclusion In this initial feasibility study, EWI was capable of characterizing local cardiac electromechanical behavior as it pertains to HF and CRT response. Activation sequences obtained with EWI allow for quantification of LV lateral wall electromechanical activation, thus providing a novel method for CRT assessment. PMID:27790723
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Reddy, Yogesh N V; Obokata, Masaru; Dean, Patrick G; Melenovsky, Vojtech; Nath, Karl A; Borlaug, Barry A
2017-06-21
Short-term studies have reported left ventricular (LV) dilatation following surgical creation of arteriovenous fistulas (AVF) or arteriovenous grafts (AVGs), but chronic cardiac structural and functional changes have not been examined or related to clinical outcomes following AVF/AVG. We sought to characterize the long-term changes in cardiac structure and function in patients undergoing shunt creation for haemodialysis. A retrospective analysis was performed of patients undergoing echocardiography before and after surgical AVF/AVG creation for the initiation of haemodialysis. 137 patients underwent echocardiographic examinations prior to AVF and 2.6 years (median) after AVF creation. Following AVF and dialysis initiation, there were reductions in blood pressure, body weight and estimated plasma volume coupled with modest reverse LV remodelling. In contrast, AVF/AVG creation was associated with significant right ventricular (RV) dilatation and deterioration in RV function. Incident heart failure (HF) developed in 43% of patients in tandem with greater RV remodeling. The development of RV dilation following surgical AVF/AVG was independently associated with increased risk of death [HR 3.9, 95% CI (1.7-9.2), P = 0.001]. In long-term follow-up, RV remodelling and dysfunction develop following AVF/AVG creation and dialysis initiation, despite improved control of LV pressure load through dialysis. Deleterious effects on right heart structure and function are coupled with development of incident HF and increased risk of death. Further study is required to identify patients at greatest risk for detrimental AVF/AVG changes who may benefit from alternate forms of dialysis or potentially ligation of existing AVF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
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Left ventricular long-axis function in treated haemochromatosis.
Davidsen, Einar Skulstad; Hervig, Tor; Omvik, Per; Gerdts, Eva
2009-03-01
We recently demonstrated reduced exercise capacity in treated genetic haemochromatosis, in spite of normal radial left ventricular (LV) systolic function assessed by 2-dimensional echocardiography at rest. It remains unknown if haemochromatosis-related impairment of LV long-axis function can be demonstrated also at rest. LV long-axis function was assessed by echocardiography including spectral tissue Doppler of systolic (S') and early (E') diastolic velocities in 105 treated haemochromatosis patients and 50 controls. Patients had higher body mass index, systolic atrioventricular excursion, and smaller LV end-systolic diameter (all P < 0.05). Other conventional echocardiographic variables did not differ. S' was normal in both groups, though significantly higher among the patients (11.1 vs. 9.9 cm/s, P < 0.001). In multiple regression analysis, higher S' was associated with having haemochromatosis, independently of significant contributions from higher atrioventricular excursion and LV length, and lower body mass index and E/E'-ratio (multiple R(2) = 0.44, P < 0.001). E' did not differ between patients and controls. However, in multivariate analysis lower E' was associated with having haemochromatosis independently of significant contributions from higher age and diastolic blood pressure, and lower transmitral E and end-diastolic LV length (multiple R(2) = 0.57, P < 0.001). The long-axis function in the haemochromatosis group was normal. Still haemochromatosis, even in this group of patients treated with regular phlebotomy, influenced both systolic and early diastolic long-axis function, and was associated with higher atrioventricular excursion and S', and with lower E'.
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Schlecht-Louf, Géraldine; Mangeney, Marianne; El-Garch, Hanane; Lacombe, Valérie; Poulet, Hervé; Heidmann, Thierry
2014-01-01
We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins that is critical for virus propagation in vivo. The envelope-mediated immunosuppression was assessed by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation (i) specifically abolishes immunosuppressive activity without affecting the "mechanical" function of the envelope protein and (ii) significantly enhances humoral and cellular immune responses elicited against the virus. The objective of this work was to study the immunosuppressive activity of the envelope protein (p15E) of feline leukemia virus (FeLV) and evaluate the effect of its abolition on the efficacy of a vaccine against FeLV. Here we demonstrate that the FeLV envelope protein is immunosuppressive in vivo and that this immunosuppressive activity can be "switched off" by targeted mutation of a specific amino acid. As a result of the introduction of the mutated envelope sequence into a previously well characterized canarypox virus-vectored vaccine (ALVAC-FeLV), the frequency of vaccine-induced FeLV-specific gamma interferon (IFN-γ)-producing cells was increased, whereas conversely, the frequency of vaccine-induced FeLV-specific interleukin-10 (IL-10)-producing cells was reduced. This shift in the IFN-γ/IL-10 response was associated with a higher efficacy of ALVAC-FeLV against FeLV infection. This study demonstrates that FeLV p15E is immunosuppressive in vivo, that the immunosuppressive domain of p15E can modulate the FeLV-specific immune response, and that the efficacy of FeLV vaccines can be enhanced by inhibiting the immunosuppressive activity of the IS domain through an appropriate mutation.
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May, Matthias; Johannsen, Manfred; Beutner, Sabine; Helke, Christian; Braun, Kay P; Lein, Michael; Roigas, Jan; Hoschke, Bernd
2006-02-01
Both laparoscopic surgery and antegrade sclerotherapy are effective treatment options in the management of varicoceles. However, very limited data comparing these two approaches are available in the literature. We present our experience regarding outcome and complications with each treatment modality. During a 10-year period, 122 cases of laparoscopic varicocelectomy (LV) and 108 cases of antegrade sclerotherapy (AS) were performed in our institution. Diagnosis and postoperative results were established clinically and using Doppler ultrasonography. Data regarding failure rate, complications, operative time and length of hospital stay of each procedure were retrospectively evaluated. Median follow-up was 59 months (5-130). Failure rates for LV and AS were 4.9% and 15.7%, respectively (p < 0.01). Complications occurred in 13.1% after LV, including 13 cases (10.7%) of hydrocele formation, and 4.6% after AS. Hydroceles following LV were significantly more frequent in patients with compared to patients without previous inguinal surgery (27.8% vs. 8.5%; p < 0.05). There was no significant difference between LV and AS regarding operative time (36 vs. 34 min, p > 0.05) and hospital stay (2.2 vs. 2.1 days, p > 0.5). In our experience, LV was more effective than AS in correcting varicoceles. Complications other than hydroceles were higher after AS. The higher incidence of postoperative hydrocele formation following LV warrants strategies such as the lymphatic sparing approach, especially in patients with previous inguinal surgery.
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Feinberg, M S; Scheinowitz, M; Laron, Z
2000-01-15
Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.
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Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients.
Eide, Per K
2008-11-01
Data from intracranial pressure (ICP) recordings in patients with hydrocephalus were reviewed to determine whether intracranial pulsatility within the cerebrospinal fluid (CSF) of cerebral ventricles (ICP(LV)) may differ from that within the brain parenchyma (ICP(PAR)), and whether pulsatility may differ between noncommunicating ventricles. The authors retrieved data from recordings previously obtained in 7 patients with hydrocephalus (noncommunicating in 4 and communicating in 3) and shunt failure who received both an external ventricular drainage (EVD) and an ICP sensor as part of surveillance during intensive care. Simultaneous ICP(LV) and ICP(PAR) signals were available in 6 cases, and simultaneous signals from the lateral and fourth ventricles (ICP(LV) and ICP4V, respectively) were recorded in 1 case. The recordings with both signals were parsed into 6-second time windows. Pulsatility was characterized by the wave amplitude and rise time coefficient, and differences in pulsatility between the ICP(LV) and ICP(PAR) signals (6 cases) or ICP(LV) and ICP4V signals (1 case) were determined. There was uneven distribution of intracranial pulsatility in all 7 patients, shown as significantly elevated pulsatility (that is, higher wave amplitudes and rise time coefficients) within the ventricles (ICP(LV)) than within brain parenchyma (ICP(PAR)) in 6 patients, and significantly higher pulsatility in the fourth (ICP4V) than in the lateral (ICP(LV)) ventricles in 1 patient. Differences > or = 1 mm Hg in ICP wave amplitude were found in 0.5-100% (median 9.4%) of observations in the 7 patients (total number of 6-second time windows, 68,242). The present observations demonstrate uneven distribution of intracranial pulsatility in patients with hydrocephalus, higher pulse pressure amplitudes within the ventricular CSF (ICP(LV)) than within the brain parenchyma (ICP(PAR)). This may be one mechanism behind ventricular enlargement in hydrocephalus.
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Soorappan, Rajasekaran Namakkal; Ahmad, Shama; Mariappan, Nithya; Litovsky, Silvio; Gupta, Himanshu; Lloyd, Steven G; Denney, Thomas S; Powell, Pamela Cox; Aban, Inmaculada; Collawn, James; Davies, James E; McGiffin, David C; Dell’Italia, Louis J
2016-01-01
Objective Recent studies have demonstrated improved outcomes in patients receiving early surgery for degenerative mitral valvular regurgitation (MR) rather than adhering to conventional guidelines for surgical intervention. However, studies providing a mechanistic basis for these findings are limited. Methods Left ventricular (LV) myocardium from 22 patients undergoing mitral valve repair for Class I indications was evaluated for desmin, the voltage-dependent anion channel, αβ-crystallin, and α, β unsaturated aldehyde 4-hydroxynonelal by fluorescence microscopy and in 6 normal control LV autopsy specimens. Cardiomyocyte ultrastructure was examined by transmission electron microscopy. Magnetic resonance imaging with tissue tagging was performed in 55 normal subjects and 22 MR patients pre- and 6 months post-mitral valve repair. Results LV end-diastolic volume was 1.5-fold (p<0.0001) higher and LV mass to volume ratio was lower in MR (p=0.004) vs. normal and improvement six months after mitral valve surgery. However, LV ejection fraction decreased from 65 ± 7 to 52 ± 9% (p<0.0001) and LV circumferential (p<0.0001) and longitudinal strain decreased significantly below normal values (p=0.002) post-surgery. MR hearts had a 53% decrease in desmin (p<0.0001) and a 2.6-fold increase in desmin aggregates (p<0.0001) vs. normal along with significant, intense perinuclear staining of α, β unsaturated aldehyde 4-hydroxynonelal in areas of mitochondrial breakdown and clustering. Transmission electron microscopy demonstrated numerous electron dense deposits, myofibrillar loss, Z-line abnormalities and extensive granulofilamentous debris identified as desmin positive by immunogold transmission electron microscopy. Conclusion Despite well-preserved preoperative LV ejection fraction, severe oxidative stress and disruption of cardiomyocyte desmin-mitochondrial sarcomeric architecture may explain post-operative LV functional decline and further supports the move toward earlier surgical intervention. PMID:27464577
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Çatli, Gönül; Kir, Mustafa; Anik, Ahmet; Yilmaz, Nuh; Böber, Ece; Abaci, Ayhan
2015-02-01
The aim of this study was to search for evidence suggesting treatment for childhood subclinical hypothyroidism (SH) by evaluating left ventricular (LV) functions of children with SH by using M-mode and tissue Doppler echocardiography (TDE). Children with SH and euthyroid healthy children (control group) were enrolled in the study. At baseline and 6 months after euthyroidism was achieved, M-mode and TDE were performed and LV functions were evaluated. Pretreatment parameters of the SH group were compared with those of controls and post-treatment parameters. 31 children with SH and 32 euthyroid healthy children were enrolled in the study. The groups had similar age, gender, puberty and body mass index. Interventricular septum thickness and LV mass index, which are the parameters for LV morphology, were slightly increased in the SH group than in the controls (p<0.05). In TDE, children with SH had significant changes in LV diastolic (lower E'm, higher E/E'm ratio and longer isovolumic relaxation time) and systolic functions (lower isovolumic contraction time) compared with controls (p<0.05). Six months after euthyroidism was achieved, TDE showed a significant improvement of some of the diastolic and systolic parameters (p<0.05). The results of this study showed that SH is associated with subclinical alterations in LV function, and LT4 replacement may improve LV systolic and diastolic parameters. However, since SH is usually a self-limiting process, these improvements in LV functions may simply be associated with the natural course of the disease and/or physiological linear growth of the children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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Weaver, Anne M; Wellenius, Gregory A; Wu, Wen-Chih; Hickson, DeMarc A; Kamalesh, Masoor; Wang, Yi
2017-03-08
Heart failure (HF) is a significant source of morbidity and mortality among African Americans. Ambient air pollution, including from traffic, is associated with HF, but the mechanisms remain unknown. The objectives of this study were to estimate the cross-sectional associations between residential distance to major roadways with markers of cardiac structure: left ventricular (LV) mass index, LV end-diastolic diameter, LV end-systolic diameter, and LV hypertrophy among African Americans. We studied baseline participants of the Jackson Heart Study (recruited 2000-2004), a prospective cohort of cardiovascular disease (CVD) among African Americans living in Jackson, Mississippi, USA. All cardiac measures were assessed from echocardiograms. We assessed the associations between residential distance to roads and cardiac structure indicators using multivariable linear regression or multivariable logistic regression, adjusting for potential confounders. Among 4826 participants, residential distance to road was <150 m for 103 participants, 150-299 m for 158, 300-999 for 1156, and ≥1000 m for 3409. Those who lived <150 m from a major road had mean 1.2 mm (95% CI 0.2, 2.1) greater LV diameter at end-systole compared to those who lived ≥1000 m. We did not observe statistically significant associations between distance to roads and LV mass index, LV end-diastolic diameter, or LV hypertrophy. Results did not materially change after additional adjustment for hypertension and diabetes or exclusion of those with CVD at baseline; results strengthened when modeling distance to A1 roads (such as interstate highways) as the exposure of interest. We found that residential distance to roads may be associated with LV end-systolic diameter, a marker of systolic dysfunction, in this cohort of African Americans, suggesting a potential mechanism by which exposure to traffic pollution increases the risk of HF.
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Agarwal, Rajiv
2016-04-01
Left ventricular (LV) hypertrophy is an established cardiovascular risk factor, yet little is known about its trajectory in people with chronic kidney disease. The goal of this prospective research study was to describe the trajectory of LV mass index, its relationship with blood pressure (BP), and specifically to compare the relationship of BP measured in the clinic and 24-hour ambulatory BP monitoring with LV mass index. Among 274 veterans with chronic kidney disease followed for over ≤ 4 years, the rate of growth of log LV mass index was inversely related to baseline LV mass index; it was rapid in the first 2 years, and plateaued subsequently. Systolic BP also significantly increased, but linearly, 1.7 mm Hg/y by clinic measurements and 1.8 mm Hg/y by 24-hour ambulatory BP. Cross-sectional and longitudinal associations of both clinic BP and 24-hour ambulatory BP with LV mass index were similar; both BP recording methods were associated with LV mass index and its growth over time. Controlled hypertension, masked uncontrolled hypertension, and uncontrolled hypertension categories had increasing LV mass index when diagnosed by 24-hour ambulatory and awake BP (P<0.05 for linear trend) but not sleep BP. After accounting for clinic BP both at baseline and longitudinally, LV mass index among individuals was additionally predicted by the difference in sleep systolic BP and clinic systolic BP (P=0.032). In conclusion, among people with chronic kidney disease, the growth of LV mass index is rapid. Research-grade clinic BP is useful to assess LV mass index and its growth over time. © 2016 American Heart Association, Inc.
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Three-dimensional changes in left and right ventricular geometry in chronic mitral regurgitation.
Young, A A; Orr, R; Smaill, B H; Dell'Italia, L J
1996-12-01
Regional three-dimensional (3-D) right (RV) and left ventricular (LV) geometry was studied in eight dogs before and 5-6 mo after induction of mitral regurgitation (MR). Ventricular shape changes were quantified with a 3-D finite-element model fitted to chamber contours traced on cardiac magnetic resonance images. MR increased LV end-diastolic volume (LVEDV; 99 vs. 57 ml; P < 0.001) and LV stroke volume (LVSV; 55 vs. 26 ml; P < 0.001). In contrast, RVEDV decreased (45 vs. 55 ml; P < 0.01), whereas SV was maintained. LV mass (free wall plus septum) increased (115 vs. 94 g; P < 0.05), whereas RV free-wall mass was relatively unchanged. Shape changes due to MR were characterized by a marked (7.4-mm) rightward shift of the septum relative to the lateral LV free wall at end diastole. In contrast, the distance from the RV free wall to the lateral LV free wall was relatively unchanged (2.7 mm). The distance between the LV lateral free wall and septum increased more than the distance between the anterior and posterior LV walls (22 vs. 15%; P = 0.04). During systole, the displacement of the septum into the LV increased significantly (7.3 vs. 2.9 mm; P < 0.01). Consistent with the end-diastolic dimension changes, LV endocardial circumferential curvature was decreased at end diastole to a greater extent in the anterior and posterior walls than in the septal and lateral walls (P < 0.01). Thus chronic MR produced an asymmetric LV dilatation with regional variation in geometry. The septum increased its contribution to the LVSV at the expense of RVEDV. RVSV was maintained, possibly by ventricular interaction.
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Degiovanni, Anna; Boggio, Enrico; Prenna, Eleonora; Sartori, Chiara; De Vecchi, Federica; Marino, Paolo N
2018-04-01
Diastolic dysfunction promotes atrial fibrillation (AF) inducing left atrial (LA) remodeling, with chamber dilation and fibrosis. Predominance of LA phasic conduit (LAC) function should reflect not only chamber alterations but also underlying left ventricular (LV) filling impairment. Thus, LAC was tested as possible predictor of early AF relapse after electrical cardioversion (EC). 96 consecutive patients, who underwent EC for persistent non-valvular AF, were prospectively enrolled. Immediately after successful EC (3 h ± 15 min), an echocardiographic apical four-chamber view was acquired with transmitral velocities, annular tissue Doppler and simultaneous LV and LA three-dimensional full-volume datasets. Then, from LA-LV volumetric curves we computed LAC as: [(LV maximum - LV minimum) - (LA maximum - LA minimum) volume], expressed as % LV stroke volume. LA pump, immediately post-EC, was assumed and verified as being negligible. Sinus rhythm persistence at 1 month was checked with ECG-Holter monitoring. At 1 month 62 patients were in sinus rhythm and 34 in AF. AF patients presented pre-EC higher E/é values (p = 0.012), no major LA volume differences (p = NS), but a stiffer LV cavity (p = 0.012) for a comparable LV capacitance (p = 0.461). Conduit contributed more (p < 0.001) to LV stroke volume in AF subpopulation. Multiple regression revealed LAC as the most significant AF predictor (p = 0.013), even after correction for biometric characteristics and pharmacotherapy (p = 0.008). Our data suggest that LAC larger contribution to LV filling soon after EC reflects LA-LV stiffening, which skews atrioventricular interaction leading to AF perpetuation and makes conduit dominance a powerful predictor of early AF recurrence.
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Changes in Liver Volume in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy
Fitzpatrick, Julie A.; Kim, Jin Un; Cobbold, Jeremy F.L.; McPhail, Mark J.W.; Crossey, Mary M.E.; Bak-Bol, Aluel A.; Zaky, Ashraf; Taylor-Robinson, Simon D.
2016-01-01
Aim Liver volumetric analysis has not been used to detect hepatic remodelling during antiviral therapy before. We measured liver volume (LV) changes on volumetric magnetic resonance imaging during hepatitis C antiviral therapy. Methods 22 biopsy-staged patients (median [range] age 4519–65 years; 9F, 13M) with chronic hepatitis C virus infection were studied. LV was measured at the beginning, end of treatment and 6 months post-treatment using 3D T1-weighted acquisition, normalised to patient weight. Liver outlines were drawn manually on 4 mm thick image slices and LV calculated. Inter-observer agreement was analysed. Patients were also assessed longitudinally using biochemical parameters and liver stiffness using Fibroscan™. Results Sustained viral response (SVR) was achieved in 13 patients with a mean baseline LV/kg of 0.022 (SD 0.004) L/kg. At the end of treatment, the mean LV/kg was 0.025 (SD 0.004, P = 0.024 cf baseline LV/kg) and 0.026 (SD 0.004, P = 0.008 cf baseline LV/kg) 6 months post-treatment (P = 0.030 cf baseline, P = 0.004). Body weight-corrected end of treatment LV change was significantly higher in patients with SVR compared to patients not attaining SVR (P = 0.050). End of treatment LV change was correlated to initial ALT (R2 = 0.479, P = 0.037), but not APRI, AST, viral load or liver stiffness measurements. There was a correlation of 0.89 between observers for measured slice thickness. Conclusions LV increased during anti-viral treatment, while the body weight-corrected LV increase persisted post-antiviral therapy and was larger in patients with SVR. PMID:27194891
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Changes in Liver Volume in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy.
Fitzpatrick, Julie A; Kim, Jin Un; Cobbold, Jeremy F L; McPhail, Mark J W; Crossey, Mary M E; Bak-Bol, Aluel A; Zaky, Ashraf; Taylor-Robinson, Simon D
2016-03-01
Liver volumetric analysis has not been used to detect hepatic remodelling during antiviral therapy before. We measured liver volume (LV) changes on volumetric magnetic resonance imaging during hepatitis C antiviral therapy. 22 biopsy-staged patients (median [range] age 45(19-65) years; 9F, 13M) with chronic hepatitis C virus infection were studied. LV was measured at the beginning, end of treatment and 6 months post-treatment using 3D T1-weighted acquisition, normalised to patient weight. Liver outlines were drawn manually on 4 mm thick image slices and LV calculated. Inter-observer agreement was analysed. Patients were also assessed longitudinally using biochemical parameters and liver stiffness using Fibroscan™. Sustained viral response (SVR) was achieved in 13 patients with a mean baseline LV/kg of 0.022 (SD 0.004) L/kg. At the end of treatment, the mean LV/kg was 0.025 (SD 0.004, P = 0.024 cf baseline LV/kg) and 0.026 (SD 0.004, P = 0.008 cf baseline LV/kg) 6 months post-treatment (P = 0.030 cf baseline, P = 0.004). Body weight-corrected end of treatment LV change was significantly higher in patients with SVR compared to patients not attaining SVR (P = 0.050). End of treatment LV change was correlated to initial ALT (R (2) = 0.479, P = 0.037), but not APRI, AST, viral load or liver stiffness measurements. There was a correlation of 0.89 between observers for measured slice thickness. LV increased during anti-viral treatment, while the body weight-corrected LV increase persisted post-antiviral therapy and was larger in patients with SVR.
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Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension
Browning, James; Schroeder, Joyce D.; Shandas, Robin; Kheyfets, Vitaly O.; Buckner, J. Kern; Hunter, Kendall S.; Hertzberg, Jean R.; Fenster, Brett E.
2016-01-01
Abstract Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e′). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = −0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e′ (Rho = 0.63, P = 0.001), and lateral e′ (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e′ (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency. PMID:27162613
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Steinhaus, Daniel A; Waks, Jonathan W; Collins, Robert; Kleckner, Karen; Kramer, Daniel B; Zimetbaum, Peter J
2015-07-01
Device longevity in cardiac resynchronization therapy (CRT) is affected by the pacing capture threshold (PCT) and programmed pacing amplitude of the left ventricular (LV) pacing lead. The aims of this study were to evaluate the stability of LV pacing thresholds in a nationwide sample of CRT defibrillator recipients and to determine potential longevity improvements associated with a decrease in the LV safety margin while maintaining effective delivery of CRT. CRT defibrillator patients in the Medtronic CareLink database were eligible for inclusion. LV PCT stability was evaluated using ≥2 measurements over a 14-day period. Separately, a random sample of 7,250 patients with programmed right atrial and right ventricular amplitudes ≤2.5 V, LV thresholds ≤ 2.5 V, and LV pacing ≥90% were evaluated to estimate theoretical battery longevity improvement using LV safety margins of 0.5 and 1.5 V. Threshold stability analysis in 43,256 patients demonstrated LV PCT stability of <0.5 V in 77% of patients and <1 V in 95%. Device longevity analysis showed that the use of a 0.5-V safety margin increased average battery longevity by 0.62 years (95% confidence interval 0.61 to 0.63) compared with a safety margin of 1.5 V. Patients with LV PCTs >1 V had the greatest increases in battery life (mean increase 0.86 years, 95% confidence interval 0.85 to 0.87). In conclusion, nearly all CRT defibrillator patients had LV PCT stability <1.0 V. Decreasing the LV safety margin from 1.5 to 0.5 V provided consistent delivery of CRT for most patients and significantly improved battery longevity. Copyright © 2015 Elsevier Inc. All rights reserved.
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Absence of left ventricular concentric hypertrophy: a prerequisite for zero coronary calcium score.
Ehara, Shoichi; Shirai, Nobuyuki; Okuyama, Takuhiro; Matsumoto, Kenji; Matsumura, Yoshiki; Yoshiyama, Minoru
2011-09-01
The identification and intervention of factors associated with a coronary artery calcification (CAC) score of zero, suggesting the absence of significant coronary artery disease (CAD) with high probability, would be meaningful in the clinical setting. Thus far, the relationship between CAC and left ventricular (LV) hypertrophy has not been documented. We identified factors associated with a CAC score of zero and evaluated the relationship between this score and LV concentric hypertrophy in 309 consecutive patients with suspected CAD who were clinically indicated to undergo multislice computed tomography angiography for coronary artery evaluation. The quantitative CAC score was calculated according to Agatston's method. The total coronary calcium score (TCS) was defined as the sum of the scores for each lesion. Four absolute TCS categories were considered: zero, mild (0-100), moderate (100-400), and severe (>400). LV hypertrophy was classified into concentric (LV mass index >104 g/m(2) in women or >116 g/m(2) in men; LV end-diastolic volume index ≤109.2 mL/m(2)) and eccentric (LV end-diastolic volume index >109.2 mL/m(2)) patterns. In the zero-TCS group, the frequency of LV concentric hypertrophy was extremely low (zero 6%, mild 17%, moderate 26%, severe 19%). Multivariate analysis revealed that age, hypercholesterolemia, diabetes mellitus, LV concentric hypertrophy, and LV mass index, but not hypertension, were the independent factors associated with a CAC score of zero. The present study demonstrated that the absence of LV concentric hypertrophy was a prerequisite for a CAC score of zero. That is, the presence of LV concentric hypertrophy, which indicated more severe underlying hypertension, long duration, or poor control of blood pressure, implicates the presence of CAC.
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Ito, Jumpei; Baba, Takuya; Kawasaki, Junna
2015-01-01
ABSTRACT Endogenous retroviruses (ERVs) are remnants of ancestral retroviral infections of germ cells. Retroviral endogenization is an adaptation process for the host genome, and ERVs are gradually attenuated or inactivated by mutation. However, some ERVs that have been “domesticated” by their hosts eventually gain physiological functions, such as placentation or viral resistance. We previously reported the discovery of Refrex-1, a soluble antiretroviral factor in domestic cats that specifically inhibits infection by feline leukemia virus subgroup D (FeLV-D), a chimeric virus of FeLV, and a feline ERV, ERV-DC. Refrex-1 is a truncated envelope protein (Env) encoded by both ERV-DC7 and ERV-DC16 proviral loci. Here, we reconstituted ancestral and functional Env from ERV-DC7 and ERV-DC16 envelope genes (env) by inducing reverse mutations. Unexpectedly, ERV-DC7 and ERV-DC16 full-length Env (ERV-DC7 fl and ERV-DC16 fl), reconstructed by removing stop codons, did not produce infectious viral particles. ERV-DC7 fl and ERV-DC16 fl were highly expressed in cells but were not cleaved into surface subunits (SU) and transmembrane subunits, nor were they incorporated into virions. G407R/N427I-A429T and Y431D substitutions within the SU C-terminal domain of ERV-DC7 fl and ERV-DC16 fl, respectively, caused these dysfunctions. The residues glycine 407 and tyrosine 431 are relatively conserved among infectious gammaretroviruses, and their substitution causes the same dysfunctions as the tested retroviruses. Our results reveal that specific mutations within the SU C-terminal domain suppressed Env cleavage and incorporation into virions and indicate that these mutations contributed to the domestication of Refrex-1 through multistep events that occurred in the postintegration period. IMPORTANCE Domestic cats are colonized with various exogenous retroviruses (exRVs), such as feline leukemia virus (FeLV), and their genomes contain numerous ERVs, some of which are replication-competent proviruses. The feline hosts, exRVs, and ERVs have complicated genetic interactions and provide an interesting field model for triangular relationships: recombination between FeLV and ERV-DC, which is a feline ERV, generated FeLV-D, a chimeric virus, and FeLV-D is restricted by Refrex-1, an antiretroviral factor corresponding to truncated Env of ERV-DC7 and ERV-DC16. Here, we reconstructed ancestral, functional Env from ERV-DC7 and ERV-DC16 env by inducing reverse mutations to elucidate how Refrex-1 was generated from its ancestor. Our results reveal that they were repeatedly inactivated by mutations preventing Env maturation. Our results provide insights into how ERVs were “domesticated” by their hosts and identify the mutations that mediated these evolutions. Notably, experiments that restore inactivated ERVs might uncover previously unrecognized features or properties of retroviruses. PMID:26581999
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Spencer, Kirk T; Weinert, Lynn; Avi, Victor Mor; Decara, Jeanne; Lang, Roberto M
2002-12-01
The Tei index is a combined measurement of systolic and diastolic left ventricular (LV) performance and may be more useful for the diagnosis of global cardiac dysfunction than either systolic or diastolic measures alone. We sought to determine whether the Tei index could be accurately calculated from LV area waveforms generated with automated border detection. Twenty-four patients were studied in 3 groups: systolic dysfunction, diastolic dysfunction, and normal. The Tei index was calculated both from Doppler tracings and from analysis of LV area waveforms. Excellent agreement was found between Doppler-derived timing intervals and the Tei index with those obtained from averaged LV area waveforms. A significant difference was seen in the Tei index, computed with both Doppler and automated border detection techniques, between the normal group and those with LV systolic dysfunction and subjects with isolated diastolic dysfunction. This study validates the use of LV area waveforms for the automated calculation of the Tei index.
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Barriers to Infection of Human Cells by Feline Leukemia Virus: Insights into Resistance to Zoonosis.
Terry, Anne; Kilbey, Anna; Naseer, Asif; Levy, Laura S; Ahmad, Shamim; Watts, Ciorsdaidh; Mackay, Nancy; Cameron, Ewan; Wilson, Sam; Neil, James C
2017-03-01
The human genome displays a rich fossil record of past gammaretrovirus infections, yet no current epidemic is evident, despite environmental exposure to viruses that infect human cells in vitro Feline leukemia viruses (FeLVs) rank high on this list, but neither domestic nor workplace exposure has been associated with detectable serological responses. Nonspecific inactivation of gammaretroviruses by serum factors appears insufficient to explain these observations. To investigate further, we explored the susceptibilities of primary and established human cell lines to FeLV-B, the most likely zoonotic variant. Fully permissive infection was common in cancer-derived cell lines but was also a feature of nontransformed keratinocytes and lung fibroblasts. Cells of hematopoietic origin were generally less permissive and formed discrete groups on the basis of high or low intracellular protein expression and virion release. Potent repression was observed in primary human blood mononuclear cells and a subset of leukemia cell lines. However, the early steps of reverse transcription and integration appear to be unimpaired in nonpermissive cells. FeLV-B was subject to G→A hypermutation with a predominant APOBEC3G signature in partially permissive cells but was not mutated in permissive cells or in nonpermissive cells that block secondary viral spread. Distinct cellular barriers that protect primary human blood cells are likely to be important in protection against zoonotic infection with FeLV. IMPORTANCE Domestic exposure to gammaretroviruses such as feline leukemia viruses (FeLVs) occurs worldwide, but the basis of human resistance to infection remains incompletely understood. The potential threat is evident from the human genome sequence, which reveals many past epidemics of gammaretrovirus infection, and from recent cross-species jumps of gammaretroviruses from rodents to primates and marsupials. This study examined resistance to infection at the cellular level with the most prevalent human cell-tropic FeLV variant, FeLV-B. We found that blood cells are uniquely resistant to infection with FeLV-B due to the activity of cellular enzymes that mutate the viral genome. A second block, which appears to suppress viral gene expression after the viral genome has integrated into the host cell genome, was identified. Since cells derived from other normal human cell types are fully supportive of FeLV replication, innate resistance of blood cells could be critical in protecting against cross-species infection. Copyright © 2017 Terry et al.
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Secchi, Francesco; Resta, Elda C; Cannaò, Paola M; Pluchinotta, Francesca; Piazza, Luciane; Butera, Gianfranco; Carminati, Mario; Sardanelli, Francesco
2017-11-01
The aim of this study was to evaluate the impact of percutaneous pulmonary valve implantation (PPVI) and surgical pulmonary valve replacement (SPVR) on biventricular and pulmonary valve function using cardiac magnetic resonance. Thirty-five patients aged 20±8 years (mean±SD) underwent PPVI, whereas 16 patients aged 30±11 years underwent SPVR. Cardiac magnetic resonance examinations were performed before and after the procedures with an average follow-up interval of 10 months. Cine steady-state free precession sequences for cardiac function and phase-contrast sequences for pulmonary flow were performed. The right ventricle (RV) and left ventricle (LV) functions were evaluated using a dedicated software. The RV end-diastolic volume index (mL/m) decreased significantly after PPVI and SPVR, from 74 to 64 (P=0.030) and from 137 to 83 (P=0.001), respectively. The RV ejection fraction increased significantly after SPVR, from 47% to 53% (P=0.038). The LV end-diastolic volume index increased significantly after PPVI, from 66 to 76 mL/m (P<0.001). The LV stroke volume index increased significantly after PPVI, from 34 to 43 mL/m (P=0.004). The analysis of bivariate correlations showed that in patients undergoing SPVR the RV changes after the procedure were positively correlated to LV changes in terms of end-systolic volume index (r=0587; P=0.017) and ejection fraction (r=0.681; P=0.004). A RV volumetric reduction and a positive effect on ventricular-ventricular interaction were observed after both PPVI and SPVR. After PPVI, a positive volumetric LV remodeling was found. No LV remodeling was found after SPVR. After both procedures, the replaced pulmonary valve functioned well.
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Fukaya, Kenji; Takeshita, Kyosuke; Okumura, Takahiro; Hiraiwa, Hiroaki; Aoki, Soichiro; Ichii, Takeo; Sugiura, Yuki; Kitagawa, Katsuhide; Kondo, Toru; Watanabe, Naoki; Kano, Naoaki; Furusawa, Kenji; Sawamura, Akinori; Morimoto, Ryota; Bando, Yasuko; Murohara, Toyoaki
2017-09-01
The clinical significance of electrocardiogram in the assessment of patients with idiopathic dilated cardiomyopathy (IDCM) is currently unknown. The aim of this study was to determine the feasibility of recording serial changes in Sokolow-Lyon voltage (∆%QRS-voltage) in one year to estimate left ventricular reverse remodeling (LVRR) and predict a prognosis of IDCM patients under tailored medical therapy. Sixty-eight consecutive patients with mild symptoms (52.1 ± 13 years old; 69% men; NYHA I/II/III/IV; 33/29/6/0) underwent electrocardiography and echocardiography at baseline and 12 month follow-up (follow-up period: 3.9 years). LVRR was observed in 30 patients (44.1%). The ∆%QRS-voltage was significantly lower in the LVRR group (LVRR; -26.9%, non-LVRR: -9.2%, p < .001). Univariate analysis showed that ∆%QRS-voltage correlated with ∆%LV end-diastolic diameter (r = .634, p < .001), and with ∆%LV ejection fraction and ∆%LV mass index (r = -.412, p < .001; r = .429, p < .001 respectively). Using receiver operating characteristic curve analysis for the estimation of LVRR, ∆%QRS of -14.7% showed optimal sensitivity (63.2%) and specificity (83.3%) (AUC = 0.775, p < .001). The composite endpoints of cardiac death (n = 0), hospitalization for advanced heart failure (n = 11) and fatal arrhythmia (n = 2) were observed in 13 patients during the follow-up period. Kaplan-Meier analysis showed significantly higher event-free rate in patients of the low ∆%QRS-voltage group (<-14.7%) (83%) than those of the high group (66%, p = .022). The present study showed that decrease in Sokolow-Lyon voltage is associated with improvement in cardiac function and favorable prognosis in IDCM patients on medical therapy, suggesting that this index is a feasible marker for response to treatment of IDCM. © 2017 Wiley Periodicals, Inc.
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Kuc, Rhoda E; Carlebur, Myrna; Maguire, Janet J; Yang, Peiran; Long, Lu; Toshner, Mark; Morrell, Nicholas W; Davenport, Anthony P
2014-11-24
In pulmonary arterial hypertension (PAH), increases in endothelin-1 (ET-1) contribute to elevated pulmonary vascular resistance which ultimately causes death by right ventricular (RV) heart failure. ET antagonists are effective in treating PAH but lack efficacy in treating left ventricular (LV) heart failure, where ETA receptors are significantly increased. The aim was to quantify the density of ETA and ETB receptors in cardiopulmonary tissue from PAH patients and the monocrotaline (MCT) rat, which recapitulates some of the pathophysiological features, including increased RV pressure. Radioligand binding assays were used to quantify affinity, density and ratio of ET receptors. In RV from human PAH hearts, there was a significant increase in the ratio of ETA to ETB receptors compared with normal hearts. In the RV of the MCT rat, the ratio also changed but was reversed. In both human and rat, there was no change in LV. In human PAH lungs, ETA receptors were significantly increased in the medial layer of small pulmonary arteries with no change detectable in MCT rat vessels. Current treatments for PAH focus mainly on pulmonary vasodilatation. The increase in ETA receptors in arteries provides a mechanism for the beneficial vasodilator actions of ET antagonists. The increase in the ratio of ETA in RV also implicates changes to ET signalling although it is unclear if ET antagonism is beneficial but the results emphasise the unexploited potential for therapies that target the RV, to improve survival in patients with PAH. Copyright © 2014. Published by Elsevier Inc.
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[Efficacy of siRNA on feline leukemia virus replication in vitro].
Lehmann, Melanie; Weber, Karin; Rauch, Gisep; Hofmann-Lehmann, Regina; Hosie, Margaret J; Meli, Marina L; Hartmann, Katrin
2015-01-01
Feline leukemia virus (FeLV) can lead to severe clinical signs in cats. Until now, there is no effective therapy for FeLV-infected cats. RNA interference-based antiviral therapy is a new concept. Specific small interfering RNA (siRNA) are designed complementary to the mRNA of a target region, and thus inhibit replication. Several studies have proven efficacy of siRNAs in inhibiting virus replication. The aim of this study was to evaluate the inhibitory potential of siRNAs against FeLV replication in vitro. siRNAs against the FeLV env gene and the host cell surface receptor (feTHTR1) which is used by FeLV-A for entry as well as siRNA that were not complementary to the FeLV or cat genome, were tested. Crandell feline kidney cells (CrFK cells) were transfected with FeLV-A/Glasgow-1. On day 13, infected cells were transfected with siRNAs. As control, cells were mock-transfected or treated with azidothymidine (AZT) (5 μg/ml). Culture supernatants were analyzed for FeLV RNA using quantitative real-time RT-PCR and for FeLV p27 by ELISA every 24 hours for five days. All siRNAs significantly reduced viral RNA and p27 production, starting after 48 hours. The fact that non-complementary siRNAs also inhibited virus replication may lead to the conclusion that unspecific mechanisms rather than specific binding lead to inhibition.
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Yang, Hui; Li, Shihao; Li, Fuhua; Wen, Rong; Xiang, Jianhai
2015-08-01
Syndecan is considered to be a multifunctional protein which functions as a cell surface receptor involved in cell adhesion, migration, cytoskeleton organization and differentiation. Previous bioinformatic analysis has revealed that syndecan in shrimp might interact with white spot syndrome virus (WSSV). In the present study, we experimentally studied the function of syndecan in shrimp immunity. The syndecan from Litopenaeus vannamei (LvSDC) was cloned and analyzed. The full-length cDNA of LvSDC was 1005 bp, consisting of 59 bp 5'-UTR, 253 bp 3'-UTR, and 693 bp open reading frame encoding 230 amino acids. LvSDC consisted of an extracellular domain (ED), a transmembrane domain (TM) and a cytoplasmic domain (CD). TM and CD shared high similarities with those of syndecan proteins from other species. LvSDC was ubiquitously expressed in all tested tissues, with the highest level in Oka. After WSSV challenge, the transcription level of LvSDC in Oka was apparently up-regulated. Recombinant LvSDC protein and its rabbit polyclonal antibody were prepared for detecting the location of LvSDC in hemocytes using immunocytochemistry approach. Data showed that LvSDC mainly located at the cell membrane and the cytoplasm of hemocytes. After silencing of LvSDC with siRNA, the WSSV copy numbers and mortality of shrimp after WSSV infection were both significantly decreased. These data provide useful information for understanding the immune mechanism of shrimp to WSSV infection. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Schwarzl, Michael; Hamdani, Nazha; Seiler, Sebastian; Alogna, Alessio; Manninger, Martin; Reilly, Svetlana; Zirngast, Birgit; Kirsch, Alexander; Steendijk, Paul; Verderber, Jochen; Zweiker, David; Eller, Philipp; Höfler, Gerald; Schauer, Silvia; Eller, Kathrin; Maechler, Heinrich; Pieske, Burkert M; Linke, Wolfgang A; Casadei, Barbara; Post, Heiner
2015-11-01
Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs (n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls (n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model. Copyright © 2015 the American Physiological Society.
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De Pergola, Giovanni; Nardecchia, Adele; Giagulli, Vito Angelo; Triggiani, Vincenzo; Guastamacchia, Edoardo; Minischetti, Manuela Castiglione; Silvestris, Franco
2013-03-01
Epidemiological studies have recently shown that obesity, and abdominal obesity in particular, is an independent risk factor for the development of heart failure (HF). Higher cardiac oxidative stress is the early stage of heart dysfunction due to obesity, and it is the result of insulin resistance, altered fatty acid and glucose metabolism, and impaired mitochondrial biogenesis. Extense myocyte hypertrophy and myocardial fibrosis are early microscopic changes in patients with HF, whereas circumferential strain during the left ventricular (LV) systole, LV increase in both chamber size and wall thickness (LV hypertrophy), and LV dilatation are the early macroscopic and functional alterations in obese developing heart failure. LV hypertrophy leads to diastolic dysfunction and subendocardial ischemia in obesity, and pericardial fat has been shown to be significantly associated with LV diastolic dysfunction. Evolving abnormalities of diastolic dysfunction may include progressive hypertrophy and systolic dysfunction, and various degrees of eccentric and/or concentric LV hypertrophy may be present with time. Once HF is established, overweight and obese have a better prognosis than do their lean counterparts with the same level of cardiovascular disease, and this phenomenon is called "obesity paradox". It is mainly due to lower muscle protein degradation, brain natriuretic peptide circulating levels and cardio-respiratory fitness than normal weight patients with HF.
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A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice.
Carbone, Salvatore; Mauro, Adolfo G; Mezzaroma, Eleonora; Kraskauskas, Donatas; Marchetti, Carlo; Buzzetti, Raffaella; Van Tassell, Benjamin W; Abbate, Antonio; Toldo, Stefano
2015-11-01
Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, exercise intolerance and cardiac dysfunction. Unhealthy diet has been associated with increased risk of obesity and heart disease, but whether it directly affects cardiac function, and promotes the development and progression of HF is unknown. We fed 8-week old male or female CD-1 mice with a standard diet (SD) or a diet rich in saturated fat and sugar, resembling a "Western" diet (WD). Cardiac systolic and diastolic function was measured at baseline and 4 and 8 weeks by Doppler echocardiography, and left ventricular (LV) end-diastolic pressure (EDP) by cardiac catheterization prior to sacrifice. An additional group of mice received WD for 4 weeks followed by SD (wash-out) for 8 weeks. WD-fed mice experienced a significant decreased in LV ejection fraction (LVEF), reflecting impaired systolic function, and a significant increase in isovolumetric relaxation time (IRT), myocardial performance index (MPI), and LVEDP, showing impaired diastolic function, without any sex-related differences. Switching to a SD after 4 weeks of WD partially reversed the cardiac systolic and diastolic dysfunction. A diet rich in saturated fat and sugars (WD) impairs cardiac systolic and diastolic function in the mouse. Further studies are required to define the mechanism through which diet affects cardiac function, and whether dietary interventions can be used in patients with, or at risk for, HF. Published by Elsevier Ireland Ltd.
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Simko, F; Potácová, A; Pelouch, V; Paulis, L; Matúsková, J; Krajcírovicová, K; Pechánová, O; Adamcová, M
2007-01-01
N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone.
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Wang, Huan; Kwak, Dongmin; Fassett, John; Liu, Xiaohong; Yao, Wu; Weng, Xinyu; Xu, Xin; Xu, Yawei; Bache, Robert J; Mueller, Daniel L; Chen, Yingjie
2017-05-01
Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c + DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c + cells and the percentage of CD11c + MHCII + (major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c + DC ablation model, we found that depletion of bone marrow-derived CD11c + DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c + DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45 + cells, CD11b + cells, CD8 + T cells and activated effector CD8 + CD44 + T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c + DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.
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Hydrogen gas improves left ventricular hypertrophy in Dahl rat of salt-sensitive hypertension.
Matsuoka, Hiroki; Miyata, Seiko; Okumura, Nozomi; Watanabe, Takuya; Hashimoto, Katsunori; Nagahara, Miki; Kato, Kazuko; Sobue, Sayaka; Takeda, Kozue; Ichihara, Masatoshi; Iwamoto, Takashi; Noda, Akiko
2018-06-14
Hypertension is an important risk factor for death resulting from stroke, myocardial infarction, and end-stage renal failure. Hydrogen (H 2 ) gas protects against many diseases, including ischemia-reperfusion injury and stroke. The effects of H 2 on hypertension and its related left ventricular (LV) function have not been fully elucidated. The purpose of this study was to investigate the effects of H 2 gas on hypertension and LV hypertrophy using echocardiography. Dahl salt-sensitive (DS) rats were randomly divided into three groups: those fed an 8% NaCl diet until 12 weeks of age (8% NaCl group), those additionally treated with H 2 gas (8% NaCl + H 2 group), and control rats maintained on a diet containing 0.3% NaCl until 12 weeks of age (0.3% NaCl group). H 2 gas was supplied through a gas flowmeter and delivered by room air (2% hydrogenated room air, flow rate of 10 L/min) into a cage surrounded by an acrylic chamber. We evaluated interventricular septal wall thickness (IVST), LV posterior wall thickness (LVPWT), and LV mass using echocardiography. IVST, LVPWT, and LV mass were significantly higher in the 8% NaCl group than the 0.3% NaCl group at 12 weeks of age, whereas they were significantly lower in the 8% NaCl + H 2 group than the 8% NaCl group. There was no significant difference in systolic blood pressure between the two groups. Our findings suggest that chronic H 2 gas inhalation may help prevent LV hypertrophy in hypertensive DS rats.
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Mouton, Alan J; Ninh, Van K; El Hajj, Elia C; El Hajj, Milad C; Gilpin, Nicholas W; Gardner, Jason D
2016-08-01
Chronic alcohol abuse is one of the leading causes of dilated cardiomyopathy (DCM) in the United States. Volume overload (VO) also produces DCM characterized by left ventricular (LV) dilatation and reduced systolic and diastolic function, eventually progressing to congestive heart failure. For this study, we hypothesized that chronic alcohol exposure would exacerbate cardiac dysfunction and remodeling due to VO. Aortocaval fistula surgery was used to induce VO, and compensatory cardiac remodeling was allowed to progress for either 3days (acute) or 8weeks (chronic). Alcohol was administered via chronic intermittent ethanol vapor (EtOH) for 2weeks before the acute study and for the duration of the 8week chronic study. Temporal alterations in LV function were assessed by echocardiography. At the 8week end point, pressure-volume loop analysis was performed by LV catheterization and cardiac tissue collected. EtOH did not exacerbate LV dilatation (end-systolic and diastolic diameter) or systolic dysfunction (fractional shortening, ejection fraction) due to VO. The combined stress of EtOH and VO decreased the eccentric index (posterior wall thickness to end-diastolic diameter ratio), increased end-diastolic pressure (EDP), and elevated diastolic wall stress. VO also led to increases in posterior wall thickness, which was not observed in the VO+EtOH group, and wall thickness significantly correlated with LV BNP expression. VO alone led to increases in interstitial collagen staining (picrosirius red), which while not statistically significant, tended to be decreased by EtOH. VO increased LV collagen I protein expression, whereas in rats with VO+EtOH, LV collagen I was not elevated relative to Sham. The combination of VO and EtOH also led to increases in LV collagen III expression relative to Sham. Rats with VO+EtOH had significantly lower collagen I/III ratio than rats with VO alone. During the acute remodeling phase of VO (3days), VO significantly increased collagen III expression, whereas this effect was not observed in rats with VO+EtOH. In conclusion, chronic EtOH accelerates the development of elevated wall stress and promotes early eccentric remodeling in rats with VO. Our data indicate that these effects may be due to disruptions in compensatory hypertrophy and extracellular matrix remodeling in response to volume overload. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Miró, G; Doménech, A; Escolar, E; Collado, V M; Tejerizo, G; De Las Heras, A; Gómez-Lucía, E
2007-05-01
The electrophoretogram of 89 cats, including those infected by feline immunodeficiency virus (FIV+), feline leukaemia virus (FeLV+) and non-infected, showed statistically significant differences in several of the fractions. FIV+ cats had very high protein values (mean, 8.10 g/dl), mostly because of hypergammaglobulinemia (mean, 2.81 g/dl) as compared with non-infected animals and FeLV+. In addition, in these FIV+ animals, the albumin/globulins ratio (A/G) was very low (mean, 0.72). Statistically significant differences in A/G and alpha2-globulin fraction were observed in FeLV+ group (A/G mean, 0.88 +/- 0.08; alpha2-globulin, mean, 0.84 +/- 0.07 g/dl) when compared with non-infected group (A/G mean, 1.06 +/- 0.08; alpha2-globulin mean, 0.68 +/- 0.04 g/dl). The alpha1-globulin fraction was higher in double infected animals (FIV and FeLV positive, F-F) (3.55 g/dl), than in FeLV+ or FIV+ cats (3.10 and 3.07 g/dl respectively), but no statistical conclusions may be drawn from this fact because of the low number of F-F animals. This technique may help to assess the initial clinical status of retrovirus-infected cats, and the clinical course of these chronic diseases, specifically during and after suitable therapy.
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Mizuno, Ju; Mohri, Satoshi; Yokoyama, Takeshi; Otsuji, Mikiya; Arita, Hideko; Hanaoka, Kazuo
2017-02-01
Varying temperature affects cardiac systolic and diastolic function and the left ventricular (LV) pressure-time curve (PTC) waveform that includes information about LV inotropism and lusitropism. Our proposed half-logistic (h-L) time constants obtained by fitting using h-L functions for four segmental phases (Phases I-IV) in the isovolumic LV PTC are more useful indices for estimating LV inotropism and lusitropism during contraction and relaxation periods than the mono-exponential (m-E) time constants at normal temperature. In this study, we investigated whether the superiority of the goodness of h-L fits remained even at hypothermia and hyperthermia. Phases I-IV in the isovolumic LV PTCs in eight excised, cross-circulated canine hearts at 33, 36, and 38 °C were analyzed using h-L and m-E functions and the least-squares method. The h-L and m-E time constants for Phases I-IV significantly shortened with increasing temperature. Curve fitting using h-L functions was significantly better than that using m-E functions for Phases I-IV at all temperatures. Therefore, the superiority of the goodness of h-L fit vs. m-E fit remained at all temperatures. As LV inotropic and lusitropic indices, temperature-dependent h-L time constants could be more useful than m-E time constants for Phases I-IV.
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Stegmann, Clara; Jahnke, Cosima; Paetsch, Ingo; Hilbert, Sebastian; Arya, Arash; Bollmann, Andreas; Hindricks, Gerhard; Sommer, Philipp
2018-02-06
Presence of late gadolinium enhancement (LGE) is related to adverse cardiovascular outcome. Many patients suffering from atrial fibrillation (AF) undergo cardiovascular magnetic resonance (CMR) imaging prior to ablation. Since quantification of atrial fibrosis still lacks reproducibility, we sought to investigate risk factors for the presence of left ventricular (LV)-LGE and a possible correlation between ventricular fibrosis as defined by positive LGE and pathological atrial voltage maps evaluated by 3D mapping systems. Between May 2015 and January 2017, 241 patients with AF (73% persistent AF, 71% male, mean age 62.8 ± 10.1 years, Redo procedure in 24%, AF history 4.5 ± 5.2 years) underwent CMR including LV LGE prior to pulmonary vein (PV) isolation at Heart Center Leipzig. Depending on CMR results, two groups were separated: 'LV-LGE negative' (Group A, n = 197, 82%) and 'LV-LGE positive' (Group B, n = 44, 18%). To identify low voltage areas (LVA), a 3D electro-anatomic map was created during PV isolation. Multivariate analysis revealed male gender [odds ratio (OR) 7.6, 95% confidence interval (95% CI) 2.4-23.9, P = 0.001] and an increased CHA2DS2VASc Score (OR 1.6, 95% CI 1.2-2.2, P = 0.004) as significantly associated with LV-LGE. Impaired left ventricular ejection fraction, LV dilatation, larger LA size and, enlarged septum diameter occurred significantly more often in the 'LGE positive' group. Low voltage areas were detected in 83 patients overall (34%): Group A: n = 64/197 (33%), Group B: n = 19/44 (43%) (P = 0.177). Male gender and high CHA2DS2VASc Score are significantly associated with presence of LV-LGE, but LV-LGE is not associated with left atrial LVA. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
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Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model.
Tveita, Torkjel; Sieck, Gary C
2012-08-01
Due to adverse effects of β-receptor agonists reported when applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a PDE3 inhibitor which mode of action is deprived the sarcolemmal β-receptor-G protein-PKA system, was tested during cooling to 15 °C. Sprague Dawley rats were instrumented to measure left ventricular (LV) pressure-volume changes using a Millar pressure-volume conductance catheter. Core temperature was reduced from 37 to 15 °C (60 min) using internal and external heat exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions for 30 min at 37 °C and during cooling. In normothermic controls continuous milrinone infusion for 90 min elevated cardiac output (CO) and stroke volume (SV) significantly. Significant differences in cardiac functional variables between the milrinone group and the saline control group during cooling to 15 °C were found: Compared to saline treated animals throughout cooling from 33 to 15 °CSV was significantly elevated in milrinone animals, the index of LV isovolumic relaxation, Tau, was significantly better preserved, and both HR and CO were significantly higher from 33 to 24 °C. Likewise, during cooling between 33 and 28 °C also LVdP/dt(max) was significantly higher in the milrinone group. Milrinone preserved LV systolic and diastolic function at a significantly higher level than in saline controls during cooling to 15 °C. In essential contrast to our previous results when using β-receptor agonists during hypothermia, the present experiment demonstrates the positive inotropic effects of milrinone on LV cardiac function during cooling to 15 °C. Copyright © 2012 Elsevier Inc. All rights reserved.
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NASA Technical Reports Server (NTRS)
Roten, L.; Nemoto, S.; Simsic, J.; Coker, M. L.; Rao, V.; Baicu, S.; Defreyte, G.; Soloway, P. J.; Zile, M. R.; Spinale, F. G.
2000-01-01
Alterations in the expression and activity of the matrix metalloproteinases (MMPs) and the tissue inhibitors of the MMPs (TIMPs) have been implicated in tissue remodeling in a number of disease states. One of the better characterized TIMPs, TIMP-1, has been shown to bind to active MMPs and to regulate the MMP activational process. The goal of this study was to determine whether deletion of the TIMP-1 gene in mice, which in turn would remove TIMP-1 expression in LV myocardium, would produce time-dependent effects on LV geometry and function. Age-matched sibling mice (129Sv) deficient in the TIMP-1 gene (TIMP-1 knock-out (TIMP-1 KO), n=10) and wild-type mice (n=10) underwent comparative echocardiographic studies at 1 and 4 months of age. LV catheterization studies were performed at 4 months and the LV harvested for histomorphometric studies. LV end-diastolic volume and mass increased (18+/-4 and 38+/-3%, respectively, P<0.05) at 4 months in the TIMP-1 KO group; a significant increase compared to wild-type controls (P<0.05). At 4 months, LV and end-diastolic wall stress was increased by over two-fold in the TIMP-1 KO compared to wild type (P<0.05). However, LV systolic pressure and ejection performance were unchanged in the two groups of mice. LV myocyte cross-sectional area was unchanged in the TIMP-1 KO mice compared to controls, but myocardial fibrillar collagen content was reduced. Changes in LV geometry occurred in TIMP-1 deficient mice and these results suggest that constitutive TIMP-1 expression participates in the maintenance of normal LV myocardial structure. Copyright 2000 Academic Press.
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Garcia, M J; Smedira, N G; Greenberg, N L; Main, M; Firstenberg, M S; Odabashian, J; Thomas, J D
2000-01-01
To determine the effect of preload in color M-mode Doppler flow propagation velocity (v(p)). The interpretation of Doppler filling patterns is limited by confounding effects of left ventricular (LV) relaxation and preload. Color M-mode v(p) has been proposed as a new index of LV relaxation. We studied four dogs before and during inferior caval (IVC) occlusion at five different inotropic stages and 14 patients before and during partial cardiopulmonary bypass. Left ventricular (LV) end-diastolic volumes (LV-EDV), the time constant of isovolumic relaxation (tau), left atrial (LA) pre-A and LV end-diastolic pressures (LV-EDP) were measured. Peak velocity during early filling (E) and v(p) were extracted by digital analysis of color M-mode Doppler images. In both animals and humans, LV-EDV and LV-EDP decreased significantly from baseline to IVC occlusion (both p < 0.001). Peak early filling (E) velocity decreased in animals from 56 +/- 21 to 42 +/- 17 cm/s (p < 0.001) without change in v(p) (from 35 +/- 15 to 35 +/- 16, p = 0.99). Results were similar in humans (from 69 +/- 15 to 53 +/- 22 cm/s, p < 0.001, and 37 +/- 12 to 34 +/- 16, p = 0.30). In both species, there was a strong correlation between LV relaxation (tau) and v(p) (r = 0.78, p < 0.001, r = 0.86, p < 0.001). Our results indicate that color M-mode Doppler v(p) is not affected by preload alterations and confirms that LV relaxation is its main physiologic determinant in both animals during varying lusitropic conditions and in humans with heart disease.
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Awadalla, Hany; Saleh, Mohamed Ayman; Abdel Kader, Mohamed; Mansour, Amr
2017-08-01
Left ventricular (LV) torsion is a novel method to assess systolic LV function. This study aimed at exploring the utility of 2D speckle tracking-based assessment of left ventricular torsion in patients with acute myocardial infarction (AMI) undertaking primary percutaneous intervention (pPCI) in predicting left ventricular remodeling. The study included 115 patients (mean±SD, age 52.2±9.67, males 84.3%) who underwent pPCI for AMI. Echocardiographic assessment of LV torsion by two-dimensional speckle tracking was performed early after the index pPCI. Patients underwent repeat echocardiography at 6 months to detect remodeling. LV torsion in the acute setting was significantly lower in those who demonstrated LV remodeling at follow-up compared to those without remodeling (7.56±1.95 vs 15.16±4.65; P<.005). Multivariate analysis identified peak CK & CK-MB elevation (β=-0.767 and -0.725; P<.001), SWMA index (β=-0.843; P<.001), and Simpson's derived LV ejection fraction (LVEF; β=0.802; P<.001) as independent predictors of baseline LV torsion. It also identified peak LV torsion (β: 0.27; 95% CI: 0.15-0.5, P=.001) and SWMA index (β: 1.07, 95% CI: 1.03-1.12, P=.005) as independent predictors of LV remodeling. Baseline Killip's grades II and higher (β: 48.6; 95% CI 5.5-428, P<.001) and diabetes mellitus (β: 29.7; 95% CI 1.1-763, P<.05) were independent predictors of mortality. Left ventricular torsion in acute MI setting is impaired and predicts subsequent LV remodeling at 6-month follow-up. © 2017, Wiley Periodicals, Inc.
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NASA Technical Reports Server (NTRS)
Garcia, M. J.; Smedira, N. G.; Greenberg, N. L.; Main, M.; Firstenberg, M. S.; Odabashian, J.; Thomas, J. D.
2000-01-01
OBJECTIVES: To determine the effect of preload in color M-mode Doppler flow propagation velocity (v(p)). BACKGROUND: The interpretation of Doppler filling patterns is limited by confounding effects of left ventricular (LV) relaxation and preload. Color M-mode v(p) has been proposed as a new index of LV relaxation. METHODS: We studied four dogs before and during inferior caval (IVC) occlusion at five different inotropic stages and 14 patients before and during partial cardiopulmonary bypass. Left ventricular (LV) end-diastolic volumes (LV-EDV), the time constant of isovolumic relaxation (tau), left atrial (LA) pre-A and LV end-diastolic pressures (LV-EDP) were measured. Peak velocity during early filling (E) and v(p) were extracted by digital analysis of color M-mode Doppler images. RESULTS: In both animals and humans, LV-EDV and LV-EDP decreased significantly from baseline to IVC occlusion (both p < 0.001). Peak early filling (E) velocity decreased in animals from 56 +/- 21 to 42 +/- 17 cm/s (p < 0.001) without change in v(p) (from 35 +/- 15 to 35 +/- 16, p = 0.99). Results were similar in humans (from 69 +/- 15 to 53 +/- 22 cm/s, p < 0.001, and 37 +/- 12 to 34 +/- 16, p = 0.30). In both species, there was a strong correlation between LV relaxation (tau) and v(p) (r = 0.78, p < 0.001, r = 0.86, p < 0.001). CONCLUSIONS: Our results indicate that color M-mode Doppler v(p) is not affected by preload alterations and confirms that LV relaxation is its main physiologic determinant in both animals during varying lusitropic conditions and in humans with heart disease.
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Park, Juri; Kim, Nan Hee; Kim, Seong Hwan; Kim, Jin-Seok; Kim, Yong Hyun; Lim, Hong Euy; Kim, Eung Ju; Na, Jin Oh; Cho, Goo-Yeong; Baik, Inkyung; Kim, Doo Man; Choi, Dong Seop; Lee, Seung Ku; Shin, Chol
2014-10-20
Obesity and low muscle mass may coexist as age-related changes in body composition. We aimed to investigate the effect of visceral adiposity and skeletal muscle mass on left ventricular (LV) structure and function in the general population. A total of 1941 participants without known cardiovascular disease were enrolled from the Korean Genome and Epidemiology Study. Visceral fat area (VFA) was assessed by computed tomography. Appendicular skeletal muscle mass (ASM) was estimated by dual-energy X-ray absorptiometry and was used as a percentage of body weight (ASM/Wt). LV structure and function were assessed by tissue Doppler imaging (TDI) echocardiography. Across VFA tertiles, ASM increased, but ASM/Wt decreased (all P<0.001). In multivariate models adjusted for conventional cardiovascular risk factors, LV mass index and LV diastolic parameters, such as left atrial dimension, TDI Ea velocity, and E/Ea ratio, were significantly impaired as VFA increased. On the other hand, an increase in ASM/Wt was associated with a decrease in LV mass index and improvement of LV diastolic parameters. With regard to LV mass index and TDI Ea velocity, VFA and ASM/Wt showed synergistic effects (all P interaction<0.05). When both VFA and ASM/Wt were simultaneously included in the same model, both remained independent predictors of LV mass index and TDI Ea velocity. More visceral fat and less muscle mass are independently and synergistically associated with an increase in LV mass index and impairment of LV diastolic parameters. Further research is needed to explore the complex mechanisms underlying these associations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Metwalley, Kotb Abbass; Farghaly, Hekma Saad; Abdelhamid, Abdelrahman
2018-01-01
This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves' disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and anti-thyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09-1.15; P = 0.001). Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves' disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function.
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Kuznetsova, Tatiana; D’hooge, Jan; Kloch-Badelek, Malgorzata; Sakiewicz, Wojciech; Thijs, Lutgarde; Staessen, Jan A.
2013-01-01
Background To understand better the mechanism of left ventricular (LV) remodeling related to hypertension, it is important to evaluate LV function in relation to the changes in loading conditions. The aim of this study was to investigate changes in conventional ventricular-arterial coupling indexes, LV strain, and a new index reflecting regional myocardial work assessed noninvasively at rest and during isometric exercise in a random sample including participants with normal blood pressure and those with hypertension. Methods A total of 148 participants (53.4% women; mean age, 52.0 years; 39.2% with hypertension) underwent simultaneous echocardiographic and arterial data acquisition at rest and during increased afterload (handgrip exercise). End-systolic pressure was determined from the carotid pulse wave. Arterial elastance (Ea) and LV elastance (Ees) were calculated as end-systolic pressure/stroke volume and end-systolic pressure/end-systolic volume. Doppler tissue imaging and two-dimensional speckle tracking were used to derive LV longitudinal strain. Regional myocardial work (ejection work density [EWD]) was the area of the pressure-strain loop during ejection. Results At rest, with adjustments applied, Ees (3.06 vs 3.71 mmHg/mL,P = .0003), Ea/Ees (0.54 vs 0.47,P=.002) and EWD (670 vs 802 Pa/m2, P = .0001) differed significantly between participants with normal blood pressure and those with hypertension. During handgrip exercise, Ea and Ea/Ees significantly increased (P < .0001) in both groups. Doppler tissue imaging and two-dimensional LV strain decreased in participants with hypertension (P ≤ .008). Only in subjects with normal blood pressure EWD significantly increased (+14.7%, P = .0009). Conclusions Although patients with hypertension compared with those with normal blood pressure have increased LV systolic stiffness and regional myocardial work to match arterial load at rest, they might have diminished cardiac reserve to increase myocardial performance, as estimated by EWD during isometric exercise. PMID:22622108
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Esteves, William Antonio M; Lodi-Junqueira, Lucas; Soares, Juliana Rodrigues; Sant'Anna Athayde, Guilherme Rafael; Goebel, Gabriela Assunção; Carvalho, Lucas Amorim; Zeng, Xin; Hung, Judy; Tan, Timothy C; Nunes, Maria Carmo Pereira
2017-12-01
The status of intrinsic left ventricular (LV) contractility in patients with isolated rheumatic mitral stenosis (MS) has been debated. The acute changes in loading conditions after percutaneous mitral valvuloplasty (PMV) may affect LV performance. We aimed to examine the acute effects of PMV on LV function and identify factors associated with LV ejection fraction (LVEF) changes, and determinants of long-term events following the procedure. One hundred and forty-two patients who underwent PMV for symptomatic rheumatic MS (valve area of 0.99±0.3cm 2 ) were prospectively enrolled. LV volumes and LVEF were measured by three-dimensional (3D) echocardiography. Long-term outcome was a composite endpoint of death, mitral valve (MV) replacement, repeat PMV, new onset of atrial fibrillation, and stroke. The mean age was 42.3±12.1years, and 125 patients were women (88%). After PMV, LVEF increased significantly (51.4 vs 56.5%, p<0.001), primary due to a significant increase in LV end-diastolic volume (65.8mL vs 67.9mL, p=0.002), and resultant increase in the stroke volume (33.9mL vs 39.6mL, p<0.001). Changes in cardiac index and systolic pulmonary artery pressure were associated with LVEF changes after PMV. During a mean follow-up period of 30.8months, 28 adverse clinical events were observed. Postprocedural mitral regurgitation, MV area, and mean gradient were independent predictors of composite endpoints. In patients with rheumatic MS, PMV resulted in a significant improvement in LV end-diastolic volume, stroke volume and consequently increased in LVEF. Changes in cardiac index and systolic pulmonary artery pressure were associated with LVEF changes after PMV. The predictors of long-term adverse events following PMV were post-procedural variables, including mitral regurgitation, valve area, and mean gradient. Copyright © 2017 Elsevier B.V. All rights reserved.
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van Bragt, Kelly A; Nasrallah, Hussein M; Kuiper, Marion; Luiken, Joost J; Schotten, Ulrich; Verheule, Sander
2014-01-01
Little is known about how atrial oxygen supply responds to increased demand, and under which conditions it falls short (supply-demand mismatch). Here, we have investigated the vasodilator response, oxygen extraction, and lactate production of the left atrium (LA) and left ventricle (LV) in response to atrial pacing and atrial fibrillation (AF). Series A (n = 9 Dutch landrace pigs) was instrumented to measure LA and LV vascular conductance in branches of the circumflex artery. Coronary conductance reserve (CCR) was calculated as the ratio between conductance during adenosine infusion and baseline. Series B (n = 7) was instrumented with sampling catheters in LA and LV veins for determination of blood gases and lactate levels. LA CCR (1.76 ± 0.14) was significantly lower than LV CCR (3.16 ± 0.27, P = 0.002). However, basal oxygen extraction was lower in LA (27 ± 3%) than that in the LV (58 ± 6%, P = 0.0006), indicating a larger extraction reserve in the LA than that in the LV (4.68 ± 0.84 vs. 1.88 ± 0.26, P = 0.01). Atrial pacing caused an increase in LA conductance (Series A) and oxygen extraction (Series B). AF increased LA vascular conductance to 177 ± 14% at 1 min, 168 ± 14 at 5 min, and 164 ± 31% at 10 min of AF (P < 0.05 vs. baseline). Atrial oxygen extraction also increased from 26 ± 3% at baseline to 63 ± 5% (P < 0.01) at 5 min and 60 ± 11% (P < 0.01) at 10 min of AF. Arterio-venous lactate difference increased significantly (P = 0.02) during AF. In healthy pigs, the LA has a lower CCR, but a higher extraction reserve compared with the LV. Although both reserves were recruited during AF, atrial lactate production increased significantly.
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Ostroumova, O D; Kochetkov, A I
2016-12-01
To assess effects of 12 weeks treatment with the amlodipine/lisinopril fixed-dose combination (ALFDC) on the left ventricular (LV) mass index (LVMI), parameters of LV and left atrial stiffness. At phase 1 of the study we examined 44 healthy subjects (21 men, 23 women, mean age 51.5+/-1.0 years) and 60 untreated patients (31 men, 29 women, mean age 53.6+/-0.8 years) with stage II grade 1-2hypertension. Myocardial stiffness parameters, LVMI were calculated using data of transthoracic echocardiography. 2-D speckle tracking echocardiography was used for determination of LV myocardial global longitudinal peak strain (GLPS). All participants underwent ambulatory blood pressure (BP) monitoring, and office BP measurement. At phase 2 a subgroup of 30 untreated patients (16 men, 14 women; mean age 52.7+/-1.11years) received ALFDC in a start dose of 5 mg/10 mg titrated every 14 days to achieve BP<140/90 mm Hg. Therapy in selected doses was continued for 12 weeks thereafter. In hypertensive patients LV GLPS was significantly lower while LA stiffness index higher compared with controls (17.08+/-0.38 vs. 19.91+/-0.41%, p<0.001, and 0.20+/-0.01 vs. 0.16+/-0.01, p<0.01, respectively). There were no significant differences in the LA tissue Doppler derived strain, LV end-systolic elastance, LA expansion index between hypertensive and control groups. After ALFDC therapy BP was significantly (p<0.001) reduced: systolic (S)BP from 154.4+/-2.7 to 130.6+/-1.2, diastolic (D)BP from 96.5+/-1.3 to 83.0+/-0.5 mm Hg. After therapy LV GLPS, LA expansion index, LV diastolic elastance significantly increased (from 17.10+/-0.57 to 18.29+/-0.35%, p<0.01; from 1.47+/-0.08 to 1.68+/-0.08, p<0.001; from 9.25+/-0.99 [10-2] to 10.88+/-1.0 8 [10-2], p<0.05, respectively) while LVMI, LV end-diastolic stiffness, and LA stiffness index significantly (p<0.001) decreased (from 129.4+/-4.5 to 111.8+/-3.3 g/m2, from 0.16+/-0.01 to 0.12+/-0.01 mm Hg/ml, from 0.21+/-0.02 to 0.15+/-0.01, respectively). Change in the LA tissue Doppler derived strain correlated with the change in dynamics of nighttime SBP (r=-0.410, p<0.05). There was direct relationship between change in LV diastolic elastance and nighttime DBP (r=0.424; p<0.05); and an inverse correlation between changes in LV end-diastolic stiffness and dynamics of the daytime SBP and DBP (r=-0.404; p<0.05 and r=-0.364; p<0.05, respectively). Change of LVMI after ALFDC treatment correlated with dynamics of 24-hour, daytime SBP, and daytime pulse pressure (r=0.382, p<0.05, r=0.478, p<0.01, and r=0.364, p<0.05, respectively). In untreated patients with stage II, 1-2 degree hypertension 12-week therapy with ALFDC allowed to achieve target BP levels, reduced severity of LV hypertrophy and improved stiffness parameters of the myocardium.
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Central adaptations in aerobic circuit versus walking/jogging trained cardiac patients.
Goodman, L S; McKenzie, D C; Nath, C R; Schamberger, W; Taunton, J E; Ammann, W C
1995-06-01
This study was done to determine (a) whether in coronary artery disease (CAD) left ventricular (LV) adaptations differed after 6 months of walking/jogging (legs-only, LO) versus aerobic circuit training (arms and legs, AL) versus a control group, and (b) whether a transfer of fitness to the untrained arms in the LO group was related to superior LV adaptations. Peak oxygen uptake for arm and leg ergometry and for cycle ergometry using radionuclide cardiac angiography were performed before and after training. Leg and arm VO2peak increased significantly by 13% in the AL group, and by 13% and 7%, respectively, for the LO group. LV function was greater after training for the LO versus the AL group. Improvements in systolic and diastolic function and a speculated hypervolemia explain these LV adaptations. In CAD patients, walking/jogging produces greater LV function improvements versus circuit training, possibly due to differences in the exercised muscle mass.
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Pantoja, Joe Luis; Ge, Liang; Zhang, Zhihong; Morrel, William G; Guccione, Julius M; Grossi, Eugene A; Ratcliffe, Mark B
2014-10-01
The role of posterior papillary muscle anchoring (PPMA) in the management of chronic ischemic mitral regurgitation (CIMR) is controversial. We studied the effect of anchoring point direction and relocation displacement on left ventricular (LV) regional myofiber stress and pump function. Previously described finite element models of sheep 16 weeks after posterolateral myocardial infarction (MI) were used. True-sized mitral annuloplasty (MA) ring insertion plus different PPM anchoring techniques were simulated. Anchoring points tested included both commissures and the central anterior mitral annulus; relocation displacement varied from 10% to 40% of baseline diastolic distance from the PPM to the anchor points on the annulus. For each reconstruction scenario, myofiber stress in the MI, border zone, and remote myocardium as well as pump function were calculated. PPMA caused reductions in myofiber stress at end-diastole and end-systole in all regions of the left ventricle that were proportional to the relocation displacement. Although stress reduction was greatest in the MI region, it also occurred in the remote region. The maximum 40% displacement caused a slight reduction in LV pump function. However, with the correction of regurgitation by MA plus PPMA, there was an overall increase in forward stroke volume. Finally, anchoring point direction had no effect on myofiber stress or pump function. PPMA reduces remote myofiber stress, which is proportional to the absolute distance of relocation and independent of anchoring point. Aggressive use of PPMA techniques to reduce remote myofiber stress may accelerate reverse LV remodeling without impairing LV function. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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Janardhanan, Rajiv; Yang, Binxia; Kilari, Sreenivasulu; Leof, Edward B; Mukhopadhyay, Debabrata; Misra, Sanjay
2016-04-01
To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 10(6) plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses. By day 21, there was a 125% increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P < .0001; day 28, P < .05; day 42, P = .59), and decrease in hypoxic stress (day 21, P < .001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels. A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.
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Fleeman, Nigel; Abdulla, Ahmed; Bagust, Adrian; Beale, Sophie; Richardson, Marty; Stainthorpe, Angela; Boland, Angela; Kotas, Eleanor; McEntee, Joanne; Palmer, Daniel
2018-03-01
The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Shire Pharmaceuticals) of pegylated liposomal irinotecan hydrochloride trihydrate (liposomal irinotecan) to submit clinical and cost-effectiveness evidence for its use in combination with 5-fluorouracil (5-FU) and folic acid/leucovorin (LV) for treating patients with pancreatic cancer following prior treatment with gemcitabine as part of the institute's Single Technology Appraisal process. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article presents a summary of the company's evidence, the ERG review and the resulting NICE guidance (TA440), issued on 26 April 2017. Clinical evidence for liposomal irinotecan + 5-FU/LV versus 5-FU/LV was derived from 236 patients with metastatic pancreatic cancer in the multinational, open-label, randomised controlled NAPOLI-1 trial. Results from analyses of progression-free survival and overall survival showed statistically significant improvements for patients treated with liposomal irinotecan + 5-FU/LV compared with those treated with 5-FU/LV. However, 5-FU/LV alone is rarely used in National Health Service clinical practice for patients with metastatic pancreatic cancer previously treated with gemcitabine. The company, ERG and Appraisal Committee (AC) all agreed that oxaliplatin + 5-FU/LV is the most commonly used treatment. Oxaliplatin + 5-FU/LV was compared with 5-FU/LV in two trials identified by the company. However, the company and the ERG both considered attempts to compare the efficacy of liposomal irinotecan + 5-FU/LV with oxaliplatin + 5-FU/LV to be methodologically flawed; not only was there heterogeneity between trials and their populations but also the proportional hazards assumption required to conduct a robust indirect treatment comparison (ITC) was violated. Nonetheless, data derived from an ITC were used to inform the company's economic model. Using the discounted patient access scheme price for liposomal irinotecan + 5-FU/LV, the company reported an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £54,412 for the comparison with oxaliplatin + 5-FU/LV. The ERG considered that the company's base-case cost-effectiveness results for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV were underestimates and should be interpreted with extreme caution. Following implementation of a number of model amendments, the ERG's modified exploratory ICER for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV was £106,898 per QALY gained. The AC accepted the majority of the ERG's amendments to the model, and also highlighted that the total QALYs for oxaliplatin + 5-FU/LV were lower than for 5-FU/LV in the company's model, which the AC considered to be clinically implausible. The AC therefore considered results from exploratory analyses, undertaken by the ERG, which included altering the QALY difference between liposomal irinotecan + 5-FU/LV and oxaliplatin + 5-FU/LV by ± 10%. These analyses resulted in ICERs for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV of between £201,019 per QALY gained to liposomal irinotecan + 5-FU/LV being dominated by oxaliplatin + 5-FU/LV. Therefore, despite uncertainty around the clinical-effectiveness evidence and cost-effectiveness results, the AC was confident that the ICER was in excess of £50,000 per QALY gained. The final guidance issued by NICE is that liposomal irinotecan + 5-FU/LV is not recommended within its marketing authorisation for treating metastatic adenocarcinoma of the pancreas in adults whose disease has progressed after gemcitabine-based therapy.
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Yang, Kai-Chien; Yamada, Kathryn A; Patel, Akshar Y; Topkara, Veli K; George, Isaac; Cheema, Faisal H; Ewald, Gregory A; Mann, Douglas L; Nerbonne, Jeanne M
2014-03-04
Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD). Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis-gene regulation represents a major mechanism of action of human cardiac lncRNAs. The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.
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Eid, Refaat A; Zaki, Mohamed Samir Ahmed; Al-Shraim, Mubarak; Eleawa, Samy M; El-Kott, Attalla Farag; Al-Hashem, Fahaid H; Eldeen, Muhammad Alaa; Ibrahim, Hoja; Aldera, Hussain; Alkhateeb, Mahmoud A
2018-05-01
This study investigated the effect of ghrelin on cardiomyocytes function, apoptosis and ultra-structural alterations of remote myocardium of the left ventricle (LV) of rats, 21 days post myocardial infarction (MI). Rats were divided into 4 groups as a control, a sham-operated rats, a sham-operated+ghrelin, an MI + vehicle and an MI + ghrelin-treated rats. MI was induced by LAD ligation and then rats were recievd a concomitant doe of either normal saline as a vehicle or treated with ghrelin (100 μg/kg S.C., 2x/day) for 21 consecutive days. Ghrelin enhanced myocardial contractility in control rats and reversed the decreases in myocardial contractility and the increases in the serum levels of CK-MB and LDH in MI-induced rats. Additionally, it inhibited the increases in levels of Bax and cleaved caspase 3 and increased those for Bcl-2 in the remote myocardium of rat's LV, post-MI. At ultra-structural level, while ghrelin has no adverse effects on LV myocardium obtained from control or sham-treated rats, ghrelin post-administration to MI-induced rats reduced vascular formation, restored normal microfilaments appearance and organization, preserved mitochondria structure, and prevented mitochondrial swelling, collagen deposition and number of ghost bodies in the remote areas of their LV. Concomitantly, in remote myocardium of MI-induced rats, ghrelin enhanced endoplasmic reticulum intracellular organelles count, decreased number of atrophied nuclei and phagocytes, diminished the irregularity in the nuclear membranes and inhibited chromatin condensation. In conclusion, in addition to the physiological, biochemical and molecular evidence provided, this is the first study that confirms the anti-apoptotic effect of ghrelin in the remote myocardium of the LV during late MI at the level of ultra-structural changes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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Takahashi, Mizuho; Yamanaka, Ayako; Asanuma, Chihiro; Asano, Hiroko; Satou, Tadaaki; Koike, Kazuo
2014-07-01
Essential oil extracted from Lavandula officinalis (LvEO) has a long history of usage in anxiety alleviation with good evidence to support its use. However, findings and information regarding the exact pathway involved and mechanism of action remain inconclusive. Therefore, we aimed to (1) reveal the influence of olfactory stimulation, and (2) determine whether the serotonergic system is involved in the anxiolytic effect of LvEO when it is inhaled. To this end, we first compared the anxiety-related behaviors of normosmic and anosmic mice. LvEO inhalation caused notable elevation in anxiety-related parameters with or without olfactory perception, indicating that olfactory stimulation is not necessarily required for LvEO to be effective. Neurochemical analysis of the serotonin (5-HT) turnover rate, accompanied by EPM testing, was then performed. LvEO significantly increased the striatal and hippocampal levels of 5-HT and decreased turnover rates in accordance with the anxiolytic behavioral changes. These results, together with previous findings, support the hypothesis that serotonergic neurotransmission plays a certain role in the anxiolytic properties of LvEO.
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Dobrowolski, Piotr; Kowalski, Mirosław; Rybicka, Justyna; Lech, Agnieszka; Tyczyński, Paweł; Witkowski, Adam; Hoffman, Piotr
2016-01-01
The aim of this study was to evaluate the potential clinical application of ultrasonic tissue indices, with a focus on systolic strain (SS) and systolic strain rate (SSR) parameters derived from transthoracic echocardiography, in the assessment of left anterior descending artery (LAD) stenosis. The data of 30 patients with significant LAD stenosis were analysed. All patients underwent transthoracic echocardiography to obtain systolic myocardial velocity (Sm), longitudinal SS, and SSR from basal, mid, and apical segments of anterior and inferior walls in two-chamber apical view. Severity of LAD obstruction was measured by means of fractional flow reserve (FFR) during coronary catheterisation. Systolic velocities, strain, and strain rate measured in basal, middle, and apical segments of the anterior left ventricular (LV) wall were lower when compared to those obtained from the corresponding, i.e. unaffected, inferior LV wall. There was a significant correlation between FFR and the value of SS, SSR characterising the apical LV segment of the anterior wall (r = -0.583, p = 0.01; r = -0.598, p = 0.01, respectively). Moreover, we found significant correlation between FFR and Sm in the mid-segment of the LV anterior wall (r = 0.611, p = 0.009). We conclude that SS and SSR obtained from the apical segment of the anterior LV wall may be related to the severity of LAD stenosis.
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Emren, Sadik Volkan; Tuluce, Selcen Yakar; Levent, Fatih; Tuluce, Kamil; Kalkan, Toygar; Yildiz, Yasar; Alacacioğlu, Ahmet; Kucukzeybek, Yüksel; Akyol, Murat; Salman, Tarık
2015-12-01
Trastuzumab, a chemotherapeutic agent used in the treatment of breast cancer. has been shown to induce subclinical left ventricular (LV) dysfunction during a three to six month period as evidenced by strain echocardiographic examination without any change occurring in the ejection fraction of LV. The present study evaluated the presence of subclinical LV dysfunction using strain echocardiography 1 day and 7 days after the initiation of trastuzumab therapy. The patients with breast cancer receiving adjuvant trastuzumab therapy underwent 2-dimensional, tissue Doppler, and strain echocardiographic examination at baseline and 1 day and 7 days after therapy. LV global longitudinal strain (GLS), global circumferential strain (GCS) values, and other echocardiographic parameters were calculated. A total of 40 females, mean age 50+/-10 years, were evaluated. Of these patients, 97% received anthracycline and 73% received radiotherapy before the initiation of trastuzumab therapy. No change was observed in any of the echocardiographic parameters 1 day after the initiation of trastuzumab therapy (p>0.05). The LV ejection fraction, tissue Doppler parameters, and GCS values did not show any changes 7 days after the initiation of therapy, whereas significant decreases were observed in GLS value (19.2+/-4.0% vs. 17.2+/-3.4, p=0.001) and systolic annular velocity of the lateral LV wall (S' velocity) (10.5+/-3.2 vs. 8.6+/-2.2, p=0.002). Trastuzumab therapy is associated with subclinical LV dysfunction as early as 7 days after initiation of the therapy as evidenced by the decreases in GLS value of LV and systolic annular velocity of the lateral LV wall.
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Influence of pacing site characteristics on response to cardiac resynchronization therapy.
Wong, Jorge A; Yee, Raymond; Stirrat, John; Scholl, David; Krahn, Andrew D; Gula, Lorne J; Skanes, Allan C; Leong-Sit, Peter; Klein, George J; McCarty, David; Fine, Nowell; Goela, Aashish; Islam, Ali; Thompson, Terry; Drangova, Maria; White, James A
2013-07-01
Transmural scar occupying left ventricular (LV) pacing regions has been associated with reduced response to cardiac resynchronization therapy (CRT). However, spatial influences of lead tip delivery relative to scar at both pacing sites remain poorly explored. This study evaluated scar distribution relative to LV and right ventricular (RV) lead tip placement through coregistration of late gadolinium enhancement MRI and cardiac computed tomographic (CT) findings. Influences on CRT response were assessed by serial echocardiography. Sixty patients receiving CRT underwent preimplant late gadolinium enhancement MRI, postimplant cardiac CT, and serial echocardiography. Blinded segmental evaluations of mechanical delay, percentage scar burden, and lead tip location were performed. Response to CRT was defined as a reduction in LV end-systolic volume ≥15% at 6 months. The mean age and LV ejection fraction were 64±9 years and 25±7%, respectively. Mean scar volume was higher among CRT nonresponders for both the LV (23±23% versus 8±14% [P=0.01]) and RV pacing regions (40±32% versus 24±30% [P=0.04]). Significant pacing region scar was identified in 13% of LV pacing regions and 37% of RV pacing regions. Absence of scar in both regions was associated with an 81% response rate compared with 55%, 25%, and 0%, respectively, when the RV, LV, or both pacing regions contained scar. LV pacing region dyssynchrony was not predictive of response. Myocardial scar occupying the LV pacing region is associated with nonresponse to CRT. Scar occupying the RV pacing region is encountered at higher frequency and seems to provide a more intermediate influence on CRT response.
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2013-01-01
Background Recently, left ventricular (LV) strain distribution pattern has been assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in terms of global LV dysfunction but with poor understanding of regional variability in LV function. We hypothesized that TIC induces specific changes in LV strain distribution pattern. Methods Twenty five adult mongrel conscious dogs were trained to lie down calmly for echocardiography. In seven selected dogs, we implanted pacing system for TIC induction under general anesthesia. We measured LV geometry and function, strains, and torsion before and after the development of TIC in awake non-sedated state. Results In 25 healthy dogs, all three types of normal strain significantly increased from base to apex (p <0.05), while a definite and recognizable twist could be measured due to presence of shear strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05), and negative peak twist rate (p <0.05). Interestingly, the relative decrease of strain due to TIC was more pronounced in the apex (p < 0.001), with the radial strain decreasing the most (p < 0.05). Conclusion TIC is accompanied by decreased systolic LV strain and twist deformation, as well as loss of early diastolic recoil. In addition, the decrease of strain was more profound in the apex. This “reverse” distribution of LV strain may help us understand LV dysfunction in the presence of nonischemic etiology. PMID:24304622
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Predictors of Renal Denervation Efficacy in the Treatment of Resistant Hypertension.
Ripp, Tatiana M; Mordovin, Victor F; Pekarskiy, Stanislav E; Ryabova, Tamara R; Zlobina, Marina V; Baev, Andrei E; Anfinogenova, Yana; Popov, Sergey V
2015-12-01
The aims of the study were to evaluate the effects of renal sympathetic denervation (RSD) on the heart and to identify the predictors of RSD efficacy in patients with resistant arterial hypertension. The study comprised 60 RSD patients (54.6 ± 9.5 years) who received full-dose antihypertensive therapy (4.1 drugs) including diuretics. Initially, 58.6% of patients had abnormal left ventricular (LV) diastolic function. All patients received echocardiography before and 24 weeks after RSD. Renal sympathetic denervation was achieved through the endovascular radiofrequency ablation (RFA) of the renal arteries. Drug therapy continued for the entire period of observation. After RSD, all patients were retrospectively assigned to two groups: group 1 comprised patients (n = 22; 36.7%) in whom the myocardial mass (MM) of the left ventricle decreased by more than 10 g after RSD; group 2 comprised patients (n = 38; 63.3%) in whom LV MM increased or decreased by less than 10 g. Anthropometry, arterial blood pressure, heart rate, therapy, and LV end-diastolic dimensions (EDD) were comparable in these groups. After RSD, the values of office blood pressure significantly decreased and MM regressed by more than 10 g in 36.7% of patients; LV diastolic function normalized in 31% of patients, and diastolic dysfunction improved in 14% of patients. The study found the associations between the initial LV wall dimensions and LV MM changes. Unlike LV EDD, arterial blood pressure, or heart rate, the initial values of LV wall thickness predicted LV MM regress. #NCT01499810 https://clinicaltrials.gov/ct2/show/NCT01499810.
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Yuan, Zengzhi; Chen, Meng; Wang, Jingting; Li, Zhuoyu; Geng, Xuyun; Sun, Jinsheng
2018-05-05
White spot syndrome virus (WSSV) is a dangerous threat to shrimp farming that also attacks a wide range of crustaceans. Knowledge of the surface protein-protein interactions between the pathogen and host is very crucial to unraveling the molecular pathogenesis mechanisms of WSSV. In this study, LvBiP (Litopenaeus vannamei immunoglobulin heavy-chain-binding protein) was identified as a novel WSSV binding protein of L. vannamei by a biotinylation based affinity chromatography method. By using pull-down and ELISA assays, the binding of recombinant LvBiP to WSSV was proved to be specific and ATP- dependent. The interaction was also confirmed by the result of co-immunoprecipitation assay. Immunofluorescence studies revealed the co-localization of LvBiP with WSSV on the cell surface of shrimp haemocytes. Additionally, LvBiP is likely to play an important role in WSSV infection. Treatment of gill cellular membrane proteins (CMPs) with purified rLvBiP and antibody that specifically recognizes LvBiP, led to a significant reduction in the binding of WSSV to gill CMPs. In the in vivo neutralization assay, rLvBiP and anti-LvBiP polyclonal antibody partially blocked the infection of WSSV. Taken together, the results indicate that LvBiP, a molecular chaperon of the HSP70 family, is a novel host factor involved at the step of attachment of the WSSV to the host cells and a potential candidate of therapeutic target. Copyright © 2018. Published by Elsevier Ltd.
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NASA Astrophysics Data System (ADS)
Mazonakis, Michalis; Grinias, Elias; Pagonidis, Konstantin; Tziritas, George; Damilakis, John
2010-02-01
The purpose of this study was to develop and evaluate a semiautomatic method for left ventricular (LV) segmentation on cine MR images and subsequent estimation of cardiac parameters. The study group comprised cardiac MR examinations of 18 consecutive patients with known or suspected coronary artery disease. The new method allowed the automatic detection of the LV endocardial and epicardial boundaries on each short-axis cine MR image using a Bayesian flooding segmentation algorithm and weighted least-squares B-splines minimization. Manual editing of the automatic contours could be performed for unsatisfactory segmentation results. The end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and LV mass estimated by the new method were compared with the reference values obtained by manually tracing the LV cavity borders. The reproducibility of the new method was determined using data from two independent observers. The mean number of endocardial and epicardial outlines not requiring any manual adjustment was more than 80% and 76% of the total contour number per study, respectively. The mean segmentation time including the required manual corrections was 2.3 ± 0.7 min per patient. LV volumes estimated by the semiautomatic method were significantly lower than those by manual tracing (P < 0.05), whereas no difference was found for EF and LV mass (P > 0.05). LV indices estimated by the two methods were well correlated (r >= 0.80). The mean difference between manual and semiautomatic method for estimating EDV, ESV, EF and LV mass was 6.1 ± 7.2 ml, 3.0 ± 5.2 ml, -0.6 ± 4.3% and -6.2 ± 12.2 g, respectively. The intraobserver and interobserver variability associated with the semiautomatic determination of LV indices was 0.5-1.2% and 0.8-3.9%, respectively. The estimation of LV parameters with the new semiautomatic segmentation method is technically feasible, highly reproducible and time effective.
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Varma, Niraj; Stadler, Robert W; Ghosh, Subham; Kloppe, Axel
2017-05-01
Cardiac resynchronization therapy (CRT) requires effective left ventricular (LV) pacing (i.e. sufficient energy and appropriate timing to capture). The AdaptivCRT™ (aCRT) algorithm serves to maintain ventricular fusion during LV or biventricular pacing. This function was tested by comparing the morphological consistency of ventricular depolarizations and percentage effective LV pacing in CRT patients randomized to aCRT vs. echo-optimization. Continuous recordings (≥20 h) of unipolar LV electrograms from aCRT (n = 38) and echo-optimized patients (n = 22) were analysed. Morphological consistency was determined by the correlation coefficient between each beat and a template beat. Effective LV pacing of paced beats was assessed by algorithmic analysis of negative initial EGM deflection in each evoked response. The %CRT pacing delivered, %effective LV pacing (i.e. % of paced beats with effective LV pacing), and overall %effective CRT (i.e. product of %CRT pacing and %effective LV pacing) were compared between aCRT and echo-optimized patients. Demographics were similar between groups. The mean correlation coefficient between individual beats and template was greater for aCRT (0.96 ± 0.03 vs. 0.91 ± 0.13, P = 0.07). Although %CRT pacing was similar for aCRT and echo-optimized (median 97.4 vs. 98.6%, P = 0.14), %effective LV pacing was larger for aCRT [99.6%, (99.1%, 99.9%) vs. 94.3%, (24.3%, 99.8%), P=0.03]. For aCRT vs. echo-optimized groups, the proportions of patients with ≥90% effective LV pacing was 92 vs. 55% (P = 0.002), and with ≥90% effective CRT was 79 vs. 45%, respectively (P = 0.018). AdaptivCRT™ significantly increased effective LV pacing over echo-optimized CRT. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
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Chuang, Michael L; Salton, Carol J; Hibberd, Mark G; Manning, Warren J; Douglas, Pamela S
2007-05-01
Three-dimensional echocardiography (3DE) allows the accurate determination of left ventricular (LV) mass, but the optimal number of component or extracted 2-dimensional (2D) image planes that should be used to calculate LV mass is not known. This study was performed to determine the relation between the number of 2D image planes used for 3DE and the accuracy of LV mass, using cardiovascular magnetic resonance (CMR) imaging as the reference standard. Three-dimensional echocardiography data sets were analyzed using 4, 6, 8, 10 and 20 component 2D planes as well as biplane 2D echocardiography and CMR in 25 subjects with a variety of LV pathologies. Repeated-measures analysis of variance and the Bland-Altman method were used to compare measures of LV mass. To further assess the potential clinical impact of reducing the number of component image planes used for 3DE, the number of discrepancies between CMR and each of the 3DE estimates of LV mass at prespecified levels (i.e., > or =5%, > or =10%, and > or =20% difference from CMR LV mass) was tabulated. The mean LV mass by magnetic resonance imaging was 177 +/- 56 g (range 91 to 316). Biplane 2-dimensional echocardiography significantly underestimated CMR LV mass (p <0.05), but LV mass by 3DE was not statistically different from that by CMR regardless of the number of planes used. However, error variability and Bland-Altman 95% confidence intervals decreased with the use of additional image planes. In conclusion, transthoracic 3DE measures LV mass more accurately than biplane 2-dimensional echocardiography when > or =6 component 2D image planes are used. The use of >6 planes further increases the accuracy of 3DE, but at the cost of greater analysis time and potentially increased scanning times.
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Agirbasli, Mehmet; Eren, Mesut; Eren, Fatih; Murphy, Sheila B; Serdar, Zehra A; Seckin, Dilek; Zara, Tuba; Cem Mat, M; Demirkesen, Cuyan; Vaughan, Douglas E
2011-07-01
Livedoid vasculopathy (LV) is a chronic, recurrent, painful cutaneous disease with distinctive clinical features and an uncertain etiology. The skin lesions are recognizable by focal purpura, depigmentation and shallow ulcers. Thrombophilic conditions occur frequently in patients with LV. While no definitive treatment exists for LV, smoking cessation, antiplatelet therapy, immunosuppressive treatment, and anabolic steroids are often included in the therapeutic ladder. Recently, a possible link between LV and impaired fibrinolysis was established as cutaneous LV lesions responded to tissue plasminogen activator (t-PA) infusion suggesting that inhibition of the fibrinolysis through plasminogen activator inhibitor-1 (PAI-1) activity may determine the disease course in patients with LV. In this study, we investigated PAI-1 antigen (Ag) and activity levels in 20 patients with biopsy proven LV (mean age 26 ± 11, M/F = 7/13, median disease duration 3.5 years). All patients received antiplatelet treatment with aspirin and/or dipyrimadole and 14 patients received anabolic steroids or immunosuppressive treatment. Fasting PAI-1 Ag and activity levels were measured at 9 AM in all patients. Both Ag (34 (26) ng/ml) (median (interquartile range)) and specific activity (17 (23) IU/fmole) levels of PAI-1 were moderately elevated in LV patients compared to the controls, however, PAI-1 kinetic studies demonstrated markedly enhanced stability of PAI-1 activity in plasma from patients with LV. Specific activity at 16 h was significantly higher than expected specific activity levels (7 (11) vs. 0.07 (0.09) IU/fmole, P < 0.01). While the exact mechanism of increased stability of PAI-1 activity is not known, it may be due to post-translational modifications or increased binding affinity for a stabilizing cofactor. In conclusion, enhanced stability of PAI-1 may contribute to the pathophysiology of LV, and systemic or local treatment with PAI-1 inhibitors may offer a potential treatment alternative in patients with LV.
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Laway, Bashir Ahmad; Ramzan, Mahroosa; Allai, Mohd Sultan; Wani, Arshad Iqbal; Misgar, Raiz Ahmad
2016-09-01
Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment. Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state. Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state. Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism. ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH = postpartum hemorrhage PWd = posterior wall diameter SS = Sheehan syndrome SV = stroke volume T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone.
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Alashi, Alaa; Mentias, Amgad; Patel, Krishna; Gillinov, A Marc; Sabik, Joseph F; Popović, Zoran B; Mihaljevic, Tomislav; Suri, Rakesh M; Rodriguez, L Leonardo; Svensson, Lars G; Griffin, Brian P; Desai, Milind Y
2016-07-01
In asymptomatic patients with ≥3+ mitral regurgitation and preserved left ventricular (LV) ejection fraction who underwent mitral valve surgery, we sought to discover whether baseline LV global longitudinal strain (LV-GLS) and brain natriuretic peptide provided incremental prognostic utility. Four hundred and forty-eight asymptomatic patients (61±12 years and 69% men) with ≥3+ primary mitral regurgitation and preserved left ventricular ejection fraction, who underwent mitral valve surgery (92% repair) at our center between 2005 and 2008, were studied. Baseline clinical and echocardiographic data (including LV-GLS using Velocity Vector Imaging, Siemens, PA) were recorded. The Society of Thoracic Surgeons score was calculated. The primary outcome was death. Mean Society of Thoracic Surgeons score, left ventricular ejection fraction, mitral effective regurgitant orifice, indexed LV end-diastolic volume, and right ventricular systolic pressure were 4±1%, 62±3%, 0.55±0.2 cm(2), 58±13 cc/m(2), and 37±15 mm Hg, respectively. Forty-five percent of patients had flail. Median log-transformed BNP and LV-GLS were 4.04 (absolute brain natriuretic peptide: 60 pg/dL) and -20.7%. At 7.7±2 years, death occurred in 41 patients (9%; 0% at 30 days). On Cox analysis, a higher Society of Thoracic Surgeons score (hazard ratio 1.55), higher baseline right ventricular systolic pressure (hazard ratio 1.11), more abnormal LV-GLS (hazard ratio 1.17), and higher median log-transformed BNP (hazard ratio 2.26) were associated with worse longer-term survival (all P<0.01). Addition of LV-GLS and median log-transformed BNP to a clinical model (Society of Thoracic Surgeons score and baseline right ventricular systolic pressure) provided incremental prognostic utility (χ(2) for longer-term mortality increased from 31-47 to 61; P<0.001). In asymptomatic patients with significant primary mitral regurgitation and preserved left ventricular ejection fraction who underwent mitral valve surgery, brain natriuretic peptide and LV-GLS provided synergistic risk stratification, independent of established factors. © 2016 American Heart Association, Inc.
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James, Susan H; Wald, Rachel; Wintersperger, Bernd J; Jimenez-Juan, Laura; Deva, Djeven; Crean, Andrew M; Nguyen, Elsie; Paul, Narinder S; Ley, Sebastian
2013-08-01
The left ventricle (LV) is routinely assessed with cardiac magnetic resonance imaging (MRI) by using short-axis orientation; it remains unclear whether the right ventricle (RV) can also be adequately assessed in this orientation or whether dedicated axial orientation is required. We used phase-contrast (PC) flow measurements in the main pulmonary artery (MPA) and the ascending aorta (Aorta) as nonvolumetric standard of reference and compared RV and LV volumes in short-axis and axial orientations. A retrospective analysis identified 30 patients with cardiac MRI data sets. Patients underwent MRI (1.5 T or 3 T), with retrospectively gated cine steady-state free-precession in axial and short-axis orientations. PC flow analyses of MPA and Aorta were used as the reference measure of RV and LV output. There was a high linear correlation between MPA-PC flow and RV-stroke volume (SV) short axis (r = 0.9) and RV-SV axial (r = 0.9). Bland-Altman analysis revealed a mean offset of 1.4 mL for RV axial and -2.3 mL for RV-short-axis vs MPA-PC flow. There was a high linear correlation between Aorta-PC flow and LV-SV short-axis (r = 0.9) and LV-SV axial (r = 0.9). Bland-Altman analysis revealed a mean offset of 4.8 m for LV short axis and 7.0 mL for LV axial vs Aorta-PC flow. There was no significant difference (P = .6) between short-axis-LV SV and short-axis-RV SV. No significant impact of the slice acquisition orientation for determination of RV and LV stroke volumes was found. Therefore, cardiac magnetic resonance workflow does not need to be extended by an axial data set for patients without complex cardiac disease for assessment of biventricular function and volumes. Copyright © 2013 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.
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Del-Pozo, J; Mishra, N; Kabuusu, R; Cheetham, S; Eldar, A; Bacharach, E; Lipkin, W I; Ferguson, H W
2017-01-01
Using transmission electron microscopy (TEM), the presented work expands on the ultrastructural findings of an earlier report on "syncytial hepatitis," a novel disease of tilapia (SHT). Briefly, TEM confirmed the presence of an orthomyxovirus-like virus within the diseased hepatocytes but not within the endothelium. This was supported by observing extracellular and intracellular (mostly intraendosomal), 60-100 nm round virions with a trilaminar capsid containing up to 7 electron-dense aggregates. Other patterns noted included enveloped or filamentous virions and virion-containing cytoplasmic membrane folds, suggestive of endocytosis. Patterns atypical for orthymyxovirus included the formation of syncytia and the presence of virions within the perinuclear cisternae (suspected to be the Golgi apparatus). The ultrastructural morphology of SHT-associated virions is similar to that previously reported for tilapia lake virus (TiLV). A genetic homology was investigated using the available reverse transcriptase polymerase chain reaction (RT-PCR) probes for TiLV and comparing clinically sick with clinically normal fish and negative controls. By RT-PCR analysis, viral nucleic acid was detected only in diseased fish. Taken together, these findings strongly suggest that a virus is causally associated with SHT, that this virus shares ultrastructural features with orthomyxoviruses, and it presents with partial genetic homology with TiLV (190 nucleotides).
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Pat, Betty; Killingsworth, Cheryl; Denney, Thomas; Zheng, Junying; Powell, Pamela; Tillson, Michael; Dillon, A Ray; Dell'Italia, Louis J
2008-12-01
The low-pressure volume overload of isolated mitral regurgitation (MR) is associated with increased adrenergic drive, left ventricular (LV) dilatation, and loss of interstitial collagen. We tested the hypothesis that beta1-adrenergic receptor blockade (beta1-RB) would attenuate LV remodeling after 4 mo of MR in the dog. beta1-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using MRI and three-dimensional (3-D) analysis, there was a 70% increase in the LV end-diastolic (LVED) volume-to-LV mass ratio, a 23% decrease in LVED midwall circumferential curvature, and a >50% increase in LVED 3-D radius/wall thickness in MR dogs that was not attenuated by beta1-RB. However, beta1-RB caused a significant increase in LVED length from the base to apex compared with untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171+/-5 microm, P<0.05) compared with normal (156+/-3 microm) and MR (165+/-4 microm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared with normal dogs (3.73+/-0.31 vs. 5.02+/-0.26%, P<0.05) and normalized with beta1-RB (4.73+/-0.48%). In addition, stimulation with the beta-adrenergic receptor agonist isoproterenol (25 nM) increased cardiomyocyte fractional shortening by 215% (P<0.05) in beta1-RB dogs compared with normal (56%) and MR (50%) dogs. In summary, beta1-RB improved LV cardiomyocyte function and beta-adrenergic receptor responsiveness despite further cell elongation. The failure to attenuate LV remodeling associated with MR could be due to a failure to improve ultrastructural changes in extracellular matrix organization.
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Pat, Betty; Chen, Yuanwen; Killingsworth, Cheryl; Gladden, James D; Shi, Ke; Zheng, Junying; Powell, Pamela C; Walcott, Greg; Ahmed, Mustafa I; Gupta, Himanshu; Desai, Ravi; Wei, Chih-Chang; Hase, Naoki; Kobayashi, Tsunefumi; Sabri, Abdelkarim; Granzier, Henk; Denney, Thomas; Tillson, Michael; Dillon, A Ray; Husain, Ahsan; Dell'italia, Louis J
2010-10-12
The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR. We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with a failure of CI to improve a 25% decrease in interstitial collagen in MR. However, LV cardiomyocyte fractional shortening was decreased in MR versus normal dogs (3.71±0.24% versus 4.81±0.31%; P<0.05) and normalized in MR+CI dogs (4.85±0.44%). MRI with tissue tagging demonstrated an increase in LV torsion angle in MR+CI versus MR dogs. CI normalized the significant decrease in fibronectin and FAK phosphorylation and prevented cardiomyocyte myofibrillar degeneration in MR dogs. In addition, total titin and its stiffer isoform were increased in the LV epicardium and paralleled the changes in fibronectin and FAK phosphorylation in MR+CI dogs. These results suggest that chymase disrupts cell surface-fibronectin connections and FAK phosphorylation that can adversely affect cardiomyocyte myofibrillar structure and function. The greater effect of CI on epicardial versus endocardial titin and noncollagen cell surface proteins may be responsible for the increase in torsion angle in chronic MR.
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NASA Technical Reports Server (NTRS)
Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.
1996-01-01
It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.
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Gözübüyük, Gökhan; Koç, Mevlüt; Kaypaklı, Onur; Şahin, Durmuş Yıldıray
2016-11-01
There are not enough data about threshold changes in patients with CRT. In this study, we aimed to investigate frequency of significant threshold increase of left ventricle lead and to determine clinical, demographic, medical and laboratory parameters that associated with threshold increase in CRT implanted patients. We included CRT implanted 200 patients (124 males, 76 females; mean age 65.8 ± 10.3 years) to this study. Basal and third month LV R wave amplitude, electrode impedance, and threshold values were recorded. Threshold increase was accepted as ≥0.1 V and significant increase as >1 V. Patients were divided into two groups: increased threshold and non-increased threshold for LV lead. Number of patients with increased LV threshold was 68 (37.6 %). Furthermore, 8 % of patients had severe increase (≥1 V) in LV threshold. We observed that serum levels of hs-CRP and 1,25 (OH)2 vitamin D were independently associated with increased LV threshold. We showed that 1 mg/dl increase in hs-CRP and the 1 mg/dl decrease in vitamin D are associated with 25.3 and 4.5 % increase in the odds of increased LV threshold, respectively. Increased hs-CRP and decreased 1,25 (OH)2 vitamin D are the strongest predictors of increased LV lead thresholds. We suggest that hs-CRP and 1,25 (OH)2 vitamin D may be used as markers to predict and follow the patients with increased thresholds. It may be useful to finalize CRT procedure with more appropriate basal threshold in patients with high serum hs-CRP and low 1,25 (OH)2 vitamin D levels.
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Canine left ventricle electromechanical behavior under different pacing modes.
Vo Thang, Thanh-Thuy; Thibault, Bernard; Finnerty, Vincent; Pelletier-Galarneau, Matthieu; Khairy, Paul; Grégoire, Jean; Harel, François
2012-10-01
Cardiac resynchronization therapy may improve survival and quality of life in patients suffering from heart failure with left ventricular (LV) contraction dyssynchrony. While several studies have investigated electrical or mechanical determinants of synchronous contraction, few have focused on activation contraction coupling at a macroscopic level. The objective of the study was to characterize LV electromechanical behavior and response to pacing in a heart failure model. We analyzed data from 3D electroanatomic non-contact mapping and blood pool SPECT for 12 dogs with right ventricular (RV) tachycardia pacing-induced dilated cardiomyopathy. Surfaces generated by the two modalities were registered. Electrical signals were analyzed, and endocardial wall displacement curves were portrayed. Rapid pacing decreased the mean LV ejection fraction (LVEF) to 20.9 % and prolonged the QRS duration to 79 ± 10 ms (normal range: 40-50 ms). QRS duration remained unchanged with biventricular pacing (88.5 ms), while single site pacing further prolonged the QRS duration (113.3 ms for RV pacing and 111.6 ms for LV pacing). No trend was observed in LV systolic function. Activation duration time was significantly increased with all pacing modes compared to baseline. Finally, electromechanical delay, as defined by the delay between electrical activation and mechanical response, was increased by single site pacing (172.9 ms for RV pacing and 174.6 ms for LV pacing) but not by biventricular pacing (162.4 ms). Combined temporal and spatial coregistration electroanatomic maps and baseline gated blood pool SPECT imaging allowed us to quantify activation duration time, electromechanical delay, and LVEF for different pacing modes. Even if pacing modes did not significantly modify LVEF or activation duration, they produced alterations in electromechanical delay, with biventricular pacing significantly decreasing the electromechanical delay as measured by surface tracings and endocardial non-contact mapping.
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Tejerizo, G; Doménech, A; Illera, J-C; Silván, G; Gómez-Lucía, E
2012-02-01
Gender differences may affect human immunodeficiency virus (HIV) infection in humans and may be related to fluctuations in sex hormone concentration. The different percentage of male and female cats observed to be infected by feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) has been traditionally explained through the transmission mechanisms of both viruses. However, sexual hormones may also play a role in this different distribution. To study this possibility, 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) concentrations were analyzed using a competitive enzyme immunoassay in the plasma of 258 cats naturally infected by FIV (FIV(+)), FeLV (FeLV(+)), or FeLV and FIV (F(-)F(+)) or negative for both viruses, including both sick and clinically healthy animals. Results indicated that the concentrations of 17β-estradiol and testosterone were significantly higher in animals infected with FIV or FeLV (P < 0.05) than in negative cats. Plasma concentrations of DHEA in cats infected by either retrovirus were lower than in negative animals (P < 0.05), and F(-)F(+) cats had significantly lower plasma values than monoinfected cats (P < 0.05). No significant differences were detected in the plasma concentration of progesterone of the four groups. No relevant differences were detected in the hormone concentrations between animal genders, except that FIV(+) females had higher DHEA concentrations than the corresponding males (P < 0.05). In addition, no differences were observed in the hormone concentrations between retrovirus-infected and noninfected animals with and without clinical signs. These results suggest that FIV and FeLV infections are associated with an important deregulation of steroids, possibly from early in the infection process, which might have decisive consequences for disease progression. Copyright © 2012 Elsevier Inc. All rights reserved.
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Patients with a hypertensive response to exercise have impaired left ventricular diastolic function.
Takamura, Takeshi; Onishi, Katsuya; Sugimoto, Tadafumi; Kurita, Tairo; Fujimoto, Naoki; Dohi, Kaoru; Tanigawa, Takashi; Isaka, Naoki; Nobori, Tsutomu; Ito, Masaaki
2008-02-01
An exaggerated increase in systolic blood pressure prolongs myocardial relaxation and increases left ventricular (LV) chamber stiffness, resulting in an increase in LV filling pressure. We hypothesize that patients with a marked hypertensive response to exercise (HRE) have LV diastolic dysfunction leading to exercise intolerance, even in the absence of resting hypertension. We recruited 129 subjects (age 63+/-9 years, 64% male) with a preserved ejection fraction and a negative stress test. HRE was evaluated at the end of a 6-min exercise test using the modified Bruce protocol. Patients were categorized into three groups: a group without HRE and without resting hypertension (control group; n=30), a group with HRE but without resting hypertension (HRE group; n=25), and a group with both HRE and resting hypertension (HTN group; n=74). Conventional Doppler and tissue Doppler imaging were performed at rest. After 6-min exercise tests, systolic blood pressure increased in the HRE and HTN groups, compared with the control group (226+/-17 mmHg, 226+/-17 mmHg, and 180+/-15 mmHg, respectively, p<0.001). There were no significant differences in LV ejection fraction, LV end-diastolic diameter, and early mitral inflow velocity among the three groups. However, early diastolic mitral annular velocity (E') was significantly lower and the ratio of early diastolic mitral inflow velocity (E) to E' (E/E') was significantly higher in patients of the HRE and HTN groups compared to controls (E': 5.9+/-1.6 cm/s, 5.9+/-1.7 cm/s, 8.0+/-1.9 cm/s, respectively, p<0.05). In conclusion, irrespective of the presence of resting hypertension, patients with hypertensive response to exercise had impaired LV longitudinal diastolic function and exercise intolerance.
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Menting, Myrthe E; McGhie, Jackie S; Koopman, Laurens P; Vletter, Wim B; Helbing, Willem A; van den Bosch, Annemien E; Roos-Hesselink, Jolien W
2016-11-01
Evaluation of left ventricular (LV) myocardial deformation by speckle tracking echocardiography (STE) is useful for clinical and research purposes. However, strain measurements depend on the used software. Normative data for QLAB 10 (Philips) are scarce. Additionally, little is known about the influence of anthropometric factors. We aimed to establish normal adult STE-derived strain and strain rate values and to evaluate associations with anthropometrics. One hundred fifty-five healthy subjects aged 20 to 72 years (≥28 subjects per decile) were prospectively gathered and examined with electrocardiography and two-dimensional echocardiography. With STE, we assessed peak systolic LV global longitudinal strain (GLS), segmental longitudinal strain, and strain rate from the three standard apical views. We included 147 healthy subjects (age 44.6±13.7 years, 50% female, GLS -20.8±2.0%). Men had significantly lower GLS than women (-20.1±1.8% vs -21.5±2.0%, P<.001). GLS was significantly lower in subjects with age above 55 years (P=.029), higher blood pressure (P<.001), higher body surface area (BSA, P<.001), larger LV end-systolic and end-diastolic volumes (both P<.001), lower LV ejection fraction (P<.001), and some indices of diastolic function. After multivariable regression analysis, the correlation with systolic blood pressure, E-wave, and LV end-systolic volume remained significant. The systolic strain rates of most segments correlated with BSA. Our study resulted in normative LV GLS values assessed with QLAB 10. Male sex, higher BSA, and higher blood pressure negatively influence GLS. Therefore, these factors should be taken into account for strain interpretation in clinical practice. © 2016, Wiley Periodicals, Inc.
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NASA Technical Reports Server (NTRS)
Tabata, Tomotsugu; Cardon, Lisa A.; Armstrong, Guy P.; Fukamach, Kiyotaka; Takagaki, Masami; Ochiai, Yoshie; McCarthy, Patrick M.; Thomas, James D.
2003-01-01
BACKGROUND: Doppler tissue echocardiography and color M-mode Doppler flow propagation velocity have proven useful in evaluating cross-sections of patients with left ventricular (LV) dysfunction, but experience with serial changes is limited. Purpose and methods: We tested their use by evaluating the temporal changes of LV function in a pacing-induced congestive heart failure model. Rapid ventricular pacing was initiated and maintained in 20 dogs for 4 weeks. Echocardiography was performed at baseline and weekly during brief pacing cessation. RESULTS: With rapid pacing, LV volume significantly increased and ejection fraction (57%-28%), stroke volume (37-18 mL), and mitral annulus systolic velocity (16.1-6.6 cm/s) by Doppler tissue echocardiography significantly decreased, with ejection fraction and mitral annulus systolic velocity closely correlated (r = 0.706, P <.0001). In contrast to the mitral inflow velocities, mitral annulus early diastolic velocity decreased steadily (12.3-7.3 cm/s) resulting in a dramatic decrease in mitral annulus early/late (1.22-0.57) diastolic velocity with no tendency toward pseudonormalization. The color M-mode Doppler flow propagation velocity also showed significant steady decrease (57-24 cm/s) throughout the pacing period. Multiple regression analysis chose mitral annulus systolic velocity (r = 0.895, P <.0001) and propagation velocity (r = 0.782, P <.0001) for the most important factor predicting LV systolic and diastolic function, respectively. CONCLUSIONS: Doppler tissue echocardiography and color M-mode Doppler flow could evaluate the serial deterioration in LV dysfunction throughout the pacing period. These were more useful in quantifying progressive LV dysfunction than conventional ehocardiographic techniques, and were probably relatively independent of preload. These techniques could be suitable for longitudinal evaluation in addition to the cross-sectional study.
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Piguet, Olivier; Leyton, Cristian E; Gleeson, Liam D; Hoon, Chris; Hodges, John R
2015-01-01
The two non-semantic variants of primary progressive aphasia (PPA), nonfluent/agrammatic PPA (nfv-PPA) and logopenic variant PPA (lv-PPA), share language features despite their different underlying pathology, and may be difficult to distinguish for non-language experts. To improve diagnostic accuracy of nfv-PPA and lv-PPA using tasks measuring non-language cognition and emotion processing. Thirty-eight dementia patients meeting diagnostic criteria for PPA (nfv-PPA 20, lv-PPA 18) and 21 matched healthy Controls underwent a comprehensive assessment of cognition and emotion processing, as well as a high-resolution structural MRI and a PiB-PET scan, a putative biomarker of Alzheimer's disease. Task performances were compared between the groups and those found to differ significantly were entered into a logistic regression analysis. Analyses revealed a double dissociation between nfv-PPA and lv-PPA. nfv-PPA exhibited significant emotion processing disturbance compared to lv-PPA and Controls. In contrast, only the lv-PPA group was significantly impaired on tasks of episodic memory. Logistic regression analyses showed that 87% of patients were correctly classified using emotion processing and episodic memory composite scores, together with a measure of visuospatial ability. Non-language presenting features can help differentiate between the two non-semantic PPA syndromes, with a double dissociation observed on tasks of episodic memory and emotion processing. Based on performance on these tasks, we propose a decision tree as a complementary method to differentiate between the two non-semantic variants. These findings have important clinical implications, with identification of patients who may potentially benefit existing therapeutic interventions currently available for Alzheimer's disease.
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Gao, Wei; Ju, Ying-Nan
2016-05-01
Patients with acute respiratory distress syndrome (ARDS) are particularly susceptible to ventilator-induced lung injury (VILI). This study investigated the effect of budesonide on VILI in a rat model of inflammatory ARDS. Forty eight rats were randomized into three groups (n = 16 each): sham group (S), endotoxin/ventilation group (LV), endotoxin/ventilation/budesonide group (LVB). Rats in the S group received anesthesia only. Rats in the LV and LVB groups received endotoxin to simulate ARDS and were mechanically ventilated for 4 h (tidal volume 30 mL/kg). Rats in the LVB group received budesonide 1 mg, and rats in the LV group received saline in airway. PaO2/FiO2, lung wet-to-dry weight ratios, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), histopathologic analysis of lung tissue, and survival were examined. PaO2/FiO2 was significantly increased in rats in the LVB group compared to the LV group. Total cell count, macrophages, and neutrophils in BALF, and levels of intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8 in BALF and serum were significantly decreased in rats in the LVB group compared to the LV group, whereas levels of IL-10 in BALF and serum were significantly increased. Histopathological changes of lung injury and apoptosis were reduced, and survival was increased in rats in the LVB group compared to the LV group. Budesonide ameliorated VILI in a rat model of inflammatory ARDS. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.
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Relationship between volume and in-hospital mortality in digestive oncological surgery.
Pérez-López, Paloma; Baré, Marisa; Touma-Fernández, Ángel; Sarría-Santamera, Antonio
2016-03-01
The results previously obtained in Spain in the study of the relationship between surgical caseload and in-hospital mortality are inconclusive. The aim of this study is to evaluate the volume-outcome association in Spain in the setting of digestive oncological surgery. An analytical, cross-sectional study was conducted with data from patients who underwent surgical procedures with curative intent of esophageal, gastric, colorectal and pancreatic neoplasms between 2006-2009 with data from the Spanish MBDS. In-hospital mortality was used as outcome variable. Control variables were patient, health care and hospital characteristics. Exposure variable was the number of interventions for each disease, dividing the hospitals in 3 categories: high volume (HV), mid volume (MV) and low volume (LV) according to the number of procedures. An inverse, statistically significant relationship between procedure volume and in-hospital mortality was observed for both volume categories in both gastric (LV: OR=1,50 [IC 95%: 1,28-1,76]; MV: OR=1,49 (IC 95%: 1,28-1,74)) and colorectal (LV: OR=1,44 [IC 95%: 1,33-1,55]; MV: OR=1,24 [IC 95%: 1,15-1,33]) cancer surgery. In pancreatic procedures, this difference was only statistically significant between LV and HV categories (LV: OR=1,89 [IC 95%: 1,29-2,75]; MV: OR=1,21 [IC 95%: 0,82-1,79]). Esophageal surgery also showed an inverse relationship, which was not statistically significant (LV: OR=1,89 [IC 95%: 0,98-3,64]; MV: OR=1,05 [IC 95%: 0,50-2,21]). The results of this study suggest the existence in Spain of an inverse relationship between caseload and in-hospital mortality in digestive oncological surgery for the procedures analyzed. Copyright © 2015 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
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Harada, Kenji; Toyono, Manotomo; Tamura, Masamichi
2004-06-01
Transthoracic Doppler echocardiography provides noninvasive measurements of coronary blood flow in the left anterior descending coronary artery (LAD). This method has the potential to show the effects of acute changes in loading conditions on blood flow. Coil closure of patent ductus arteriosus (PDA) is a model of acute changes in blood pressure and left ventricular (LV) preload that influences coronary blood flow. We applied this technique to assess the coronary blood flow changes for patients with PDA before and immediately after PDA coil closure. We examined 9 patients (1.8 +/- 1.1 years) with simple PDA and 8 age-matched healthy children. LV dimensions and LV mass were measured. Maximum peak flow velocity and flow volume in the LAD were measured. Pulmonary to systemic flow ratios (Qp/Qs) were obtained by cardiac catheterization. After PDA coil closure, LV end-diastolic dimension decreased, and systolic and diastolic blood pressures increased significantly. The maximum peak flow velocity, LAD flow volume, and the ratio of LAD flow volume to LV mass increased significantly. The changes in maximum peak flow velocity and the ratio of LAD flow volume to LV mass (F/M) correlated positively with the changes in diastolic pressure and Qp/Qs. In 5 patients who had Qp/Qs > 1.5, the mean F/M was significantly lower compared with control subjects, but they increased to normal values after coil closure of PDA. PDA coil closure increases diastolic pressure and decreases Qp/Qs, resulting in improvement of myocardial perfusion. These findings provide new insights into the relationship between cardiac function and coronary circulation in pediatric patients with heart diseases associated with PDA.
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Terada, Tomomasa; Mori, Kazuhiro; Inoue, Miki; Yasunobu, Hayabuchi
2016-11-01
Assessment of longitudinal left ventricular (LV) function is important for early detection of cardiac dysfunction. Although mitral annular plane systolic excursion (MAPSE) obtained by M-mode echocardiography offers a simple method for assessing longitudinal LV function, normal values of MAPSE for children change according to body size. To minimize the effects of body size, MAPSE was divided by LV long-axis length (MAPSE/L). MAPSE/L was measured in 210 healthy children from birth to 15 years of age and classified into five subgroups. MAPSE/L was then compared with 10 parameters in 136 children (age, heart rate, mean blood pressure, ejection fraction of the LV (EF), peak atrial flow velocity/peak early diastolic flow velocity of mitral flow, tissue Doppler velocity during systole (s') and early diastole (e'), E/e' ratio, Tei index, and global longitudinal strain (GLS) of the LV by the speckle tracking method). MAPSE/L was significantly lower in the neonate group than in the remaining four groups. MAPSE/L then increased with age to peak at 1-5 years and gradually decreased thereafter. In all cases beyond the neonatal period, MAPSE/L was more than 0.17. Among various parameters, GLS, age, EF, Tei index and s' were significantly associated with MAPSE/L in that order. In univariate analysis, GLS was most significantly associated with MAPSE/L (r=.56). We have established normal reference values for MPSE/L in healthy children. MAPSE/L is expected to offer a simple parameter to evaluate LV longitudinal systolic function during daily routine echocardiography in children. © 2016, Wiley Periodicals, Inc.
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Vertilus, Shawyntee M.; Austin, Stephanie L.; Foster, Kimberly S.; Boyette, Keri E.; Bali, Deeksha; Li, Jennifer S.; Kishnani, Priya S.; Wechsler, Stephanie Burns
2013-01-01
Purpose Glycogen Storage Disease (GSD) type III, glycogen debranching enzyme deficiency, causes accumulation of glycogen in liver, skeletal, and cardiac muscle. Some patients develop increased left ventricular (LV) thickness by echocardiography, but the rate of increase and its significance remain unclear. Methods We evaluated 33 patients with GSD type III, 23 with IIIa and 10 with IIIb, ages 1 month – 55.5 yrs, by echocardiography for wall thickness, LV mass, shortening and ejection fractions, at 1 time point (n = 33) and at 2 time points in patients with more than 1 echocardiogram (13 of the 33). Results Of 23 cross-sectional patients with type IIIa, 12 had elevated LV mass, 11 had elevated wall thickness. One type IIIb patient had elevated LV mass but 4 had elevated wall thickness. For those with multiple observations, 9 of 10 with type IIIa developed increased LV mass over time, with 3 already increased at first measurement. Shortening and ejection fractions were generally normal. Conclusion Elevated LV mass and wall thickness is more common in patients with type IIIa but develops rarely in type IIIb, though ventricular systolic function is preserved. This suggests serial echocardiograms with attention to LV thickness and mass are important for care of these patients. PMID:20526204
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O’Hara, Michael W.; Segre, Lisa S.
2017-01-01
Maternal depression is a prevalent public health problem, particularly for low-income mothers of young children. Intervention development efforts, which often focus on surmounting instrumental barriers to care, have not successfully engaged and retained women in treatment. Task-sharing approaches like Listening Visits (LV) could overcome key instrumental and psychological barriers by leveraging the access of trusted, community caregivers to deliver treatment. A recent randomized controlled trial (RCT) demonstrated the efficacy of LV delivered by non-mental-health providers as compared to usual care. The present report presents results from a follow-up phase of that RCT during which participants who had completed LV were followed for an additional 8 weeks and completed measures of depression and quality of life. In addition, participants who were initially randomized to the wait-list control group received LV and were assessed. Treatment gains previously observed in participants completing LV were enhanced during the 8-week follow-up period. Participants receiving LV during the follow-up period experienced significant improvement in depressive symptoms. Results demonstrate the sustainability of LV delivered by non-mental-health providers, and provide preliminary evidence for the replicability of this approach in a sample of predominately low-income pregnant women and mothers of young children. PMID:28349604
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Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D
2012-10-01
Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 μg/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (p<0.0001). This was associated with a trend of higher Tb.N, Tb.Th, DA, an inferior Conn.D and a lower bone turnover as shown by the decreases of osteoid parameters, MS/BS, Ac.f in LV1 when compared to IC. In addition, the ratio PYD/DPD was 4 times higher in LV1 than IC. After 3 months, significant decreases of sALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly only in LV1 (p<0.05) with a trend of increases in MS/BS and BFR/BS, compared to LV1-CTRL. In conclusion, in adult ewes, the bone mass, microarchitecture, remodeling and collagen crosslink content differ according to the bone site (iliac crest and vertebra). Furthermore, after 3 months, the responses to ZOL and TPTD were of different magnitude and delay between the two bone sites. The distinction of bone sites to study the early effects of anti-osteoporotic therapies appears meaningful in order to approach their site-specific anti-fracture efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.
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Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F; Salton, Carol J; Blease, Susan J; Yeon, Susan B; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J
2012-11-01
The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF). Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized. Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension. In the referent group (mean age 61 ± 9 years; 262 men and 423 women), mean TPM was 23 ± 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool. Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Utsunomiya, Hiroto; Yamamoto, Hideya; Kunita, Eiji; Hidaka, Takayuki; Kihara, Yasuki
2014-04-27
Insulin resistance, as a key mediator of metabolic syndrome, is thought to be associated with pathogenesis of calcific aortic valve disease and altered left ventricular (LV) function and structure. However, in patients with aortic valve sclerosis (AVS), the association between insulin resistance and subclinical impairment of LV function is not fully elucidated. We studied 57 patients (mean age 70 ± 8 years, 22 women) with asymptomatic AVS but normal LV ejection fraction in echocardiography. LV longitudinal and circumferential strain and strain rate was analyzed using two-dimensional speckle tracking echocardiography. Patients with uncontrolled hypertension and diabetes mellitus, chronic kidney disease, and concomitant coronary artery disease were excluded. They were divided into the insulin-resistant group (AVS+IR; N = 28) and no insulin-resistant group (AVS-IR; N = 29) according to the median value of homeostatic model assessment index. Computed tomography scans were also performed to measure the aortic valve calcium score and the visceral adipose tissue (VAT) area. In addition, age- and sex- adjusted 28 control subjects were recruited for the comparison. There were no significant differences in LV ejection fraction or mass index among the groups. The AVS+IR group had a higher aortic valve calcium score (median 94 versus 21, P = 0.022) and a larger VAT area (113 ± 42 cm2 versus 77 ± 38 cm2, P = 0.001) than the AVS-IR group. Notably, LV global longitudinal strain, strain rate (SR), and early diastolic SR were significantly lower in the AVS+IR group than in the AVS-IR group and in control subjects (strain: -16.2 ± 1.6% versus -17.2 ± 1.2% and -18.9 ± 0.8%; SR: -1.18 ± 0.26 s(-1) versus -1.32 ± 0.21 s(-1) and -1.52 ± 0.08 s(-1); early diastolic SR: -1.09 ± 0.23 s(-1) versus -1.23 ± 0.18 s(-1) and -1.35 ± 0.12 s(-1); P < 0.05 for all comparison), whereas circumferential function were not significantly different. Multiple linear regression analyses revealed insulin resistance as an independent determinant of LV longitudinal strain (P = 0.017), SR (P = 0.047), and early diastolic SR (P = 0.049) regardless of LV mass index or VAT area. Insulin resistance is a powerful independent predictor of subclinical LV dysfunction regardless of concomitant visceral obesity and LV hypertrophy. Thus, it may be a novel therapeutic target to prevent subsequent heart failure in patients with AVS.
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Cheng, Yanping; Yi, Geng-Hua; Annest, Lon S; Van Bladel, Kevin; Brown, Ryan; Wechsler, Andrew; Shibuya, Masahiko; Conditt, Gerard B; Peppas, Athanasios; Kaluza, Greg L; Granada, Juan F
2015-04-01
To test the feasibility of a thoracoscopically assisted, off-pump, transcatheter ventricular reconstruction (TCVR) approach in an ovine model of left ventricular (LV) anteroapical aneurysm. Myocardial infarction (MI) was induced by coil occlusion of the middle left anterior descending artery and diagonals. Two months after MI creation, TCVR was performed via a minimal thoracotomy in eight sheep. Under endoscopic and fluoroscopic guidance, trans-interventricular septal puncture was performed from the LV epicardial scar. A guidewire was externalised via a snare placed in the right ventricle from the external jugular vein. An internal anchor was inserted over the wire and positioned on the right ventricular septum and an external anchor was deployed on the LV anterior epicardium. Serial pairs of anchors were placed and plicated together to exclude the scar completely. Immediately after TCVR, echocardiography showed LV end-systolic volume decreased from pre-procedure 58.8±16.6 ml to 25.1±7.6 ml (p<0.01) and the ejection fraction increased from 32.0±7.3% to 52.0±7.5% (p<0.01). LV twist significantly improved (3.83±2.21 vs. pre-procedure -0.41±0.94, p=0.01) and the global peak-systolic longitudinal strain increased from -5.64% to -10.77% (p<0.05). TCVR using minimally invasive access techniques on the off-pump beating heart is feasible and resulted in significant improvement in LV performance.
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NASA Technical Reports Server (NTRS)
Shiota, T.; McCarthy, P. M.; White, R. D.; Qin, J. X.; Greenberg, N. L.; Flamm, S. D.; Wong, J.; Thomas, J. D.
1999-01-01
The geometry of the left ventricle in patients with cardiomyopathy is often sub-optimal for 2-dimensional ultrasound when assessing left ventricular (LV) function and localized abnormalities such as a ventricular aneurysm. The aim of this study was to report the initial experience of real-time 3-D echocardiography for evaluating patients with cardiomyopathy. A total of 34 patients were evaluated with the real-time 3D method in the operating room (n = 15) and in the echocardiographic laboratory (n = 19). Thirteen of 28 patients with cardiomyopathy and 6 other subjects with normal LV function were evaluated by both real-time 3-D echocardiography and magnetic resonance imaging (MRI) for obtaining LV volumes and ejection fractions for comparison. There were close relations and agreements for LV volumes (r = 0.98, p <0.0001, mean difference = -15 +/- 81 ml) and ejection fractions (r = 0.97, p <0.0001, mean difference = 0.001 +/- 0.04) between the real-time 3D method and MRI when 3 cardiomyopathy cases with marked LV dilatation (LV end-diastolic volume >450 ml by MRI) were excluded. In these 3 patients, 3D echocardiography significantly underestimated the LV volumes due to difficulties with imaging the entire LV in a 60 degrees x 60 degrees pyramidal volume. The new real-time 3D echocardiography is feasible in patients with cardiomyopathy and may provide a faster and lower cost alternative to MRI for evaluating cardiac function in patients.
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Luijkx, Tim; Velthuis, Birgitta K; Backx, Frank J G; Buckens, Constantinus F M; Prakken, Niek H J; Rienks, Rienk; Mali, Willem P Th M; Cramer, Maarten J
2013-08-10
Uncertainty remains about possible cardiac adaptation to resistance training. Androgenic anabolic steroids (AAS) use plays a potential role and may have adverse cardiovascular effects. To elucidate the effect of resistance training and of AAS-use on cardiac dimensions and function. Cardiac magnetic resonance (CMR) were performed in 156 male subjects aged 18-40 years: 52 non-athletes (maximum of 3 exercise hours/week), 52 strength-endurance (high dynamic-high static, HD-HS) athletes and 52 strength (low dynamic-high static, LD-HS) trained athletes (athletes ≥ 6 exercise hours/week). 28 LD-HS athletes denied and 24 admitted to AAS use for an average duration of 5 years (range 3 months-20 years). No significant differences were found between non-athletes and non-AAS-using LD-HS athletes. AAS-using LD-HS athletes had significantly larger LV and RV volumes and LV wall mass than non-AAS-using LD-HS athletes, but lower than HD-HS athletes. In comparison to all other groups AAS-using LD-HS athletes showed lower ejection fractions of both ventricles (LV/RV EF 51/48% versus 55-57/51-52%) and lower E/A ratios (LV/RV 1.5/1.2 versus 1.9-2.0/1.4-1.5) as an indirect measure of diastolic function. Linear regression models demonstrated a significant effect of AAS-use on LV EDV, LV EDM, systolic function and mitral valve E/A ratio (all ANOVA-tests p<0.05). Strength athletes who use AAS show significantly different cardiac dimensions and biventricular systolic dysfunction and impaired ventricular inflow as compared to non-athletes and non-AAS-using strength athletes. Increased ventricular volume and mass did not exceed that of strength-endurance athletes. These findings may help raise awareness of the consequences of AAS use. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Ogawa, Kiyohiro; Hirooka, Yoshitaka; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji
2013-01-01
Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure. MI-induced heart failure model rats were created by ligation of left coronary artery. The expression level of TLR4 in brainstem was significantly higher in MI-induced heart failure treated with intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in brainstem was significantly lower in MI-induced heart failure treated with ICV injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA. Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were significantly lower and LV dimension was significantly smaller in MI-induced heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for 2 weeks. Partially silencing brain TLR4 by ICV injection of TLR4-SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of the treatment for MI-induced heart failure.
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Effect of balloon mitral valvotomy on left ventricular function in rheumatic mitral stenosis.
Rajesh, Gopalan Nair; Sreekumar, Pradeep; Haridasan, Vellani; Sajeev, C G; Bastian, Cicy; Vinayakumar, D; Kadermuneer, P; Mathew, Dolly; George, Biju; Krishnan, M N
Mitral stenosis (MS) is found to produce left ventricular (LV) dysfunction in some studies. We sought to study the left ventricular function in patients with rheumatic MS undergoing balloon mitral valvotomy (BMV). Ours is the first study to analyze effect of BMV on mitral annular plane systolic excursion (MAPSE), and to quantify prevalence of longitudinal left ventricular dysfunction in rheumatic MS. In this prospective cohort study, we included 43 patients with severe rheumatic mitral stenosis undergoing BMV. They were compared to twenty controls whose distribution of age and gender were similar to that of patients. The parameters compared were LV ejection fraction (EF) by modified Simpson's method, mitral annular systolic velocity (MASV), MAPSE, mitral annular early diastolic velocity (E'), and myocardial performance index (MPI). These parameters were reassessed immediately following BMV and after 3 months of procedure. MASV, MAPSE, E', and EF were significantly lower and MPI was higher in mitral stenosis group compared to controls. Impaired longitudinal LV function was present in 77% of study group. MAPSE and EF did not show significant change after BMV while MPI, MASV, and E' improved significantly. MASV and E' showed improvement immediately after BMV, while MPI decreased only at 3 months follow-up. There were significantly lower mitral annular motion parameters including MAPSE in patients with rheumatic mitral stenosis. Those with atrial fibrillation had higher MPI. Immediately after BMV, there was improvement in LV long axis function with a gradual improvement in global LV function. There was no significant change of MAPSE after BMV. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.
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Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles
2016-06-01
Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death. The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 μM) and L-type calcium current (ICa) blocker verapamil (2-3 μM) were used to induce an early repolarization pattern and PVT. After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 μM), 6 of 7 by milrinone (2.5 μM), and 7 of 8 by isoproterenol (0.1-1 μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current during the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
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Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles
2016-01-01
Background Early Repolarization Syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and fibrillation (VF), leading to sudden cardiac death. Objective The present study tests the hypothesis that the Ito-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Methods Transmembrane action potentials (AP) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left-ventricular (LV) wedge preparations, together with a transmural pseudo-ECG. The Ito-agonist NS5806 (7–15 μM) and ICa-blocker verapamil (2–3 uM) were used to induce an ER pattern and PVT. Results Following stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase-2-reentry (P2R) and PVT. Arrhythmic activity was suppressed in 7/8 preparations by cilostazol (10 μM), 6/7 by milrinone (2.5 μM) and 7/8 by isoproterenol (0.1–1μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Conclusions Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current in the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying development of P2R and VT/VF. PMID:26820510
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Improved arterial-ventricular coupling in metabolic syndrome after exercise training: a pilot study.
Fournier, Sara B; Donley, David A; Bonner, Daniel E; Devallance, Evan; Olfert, I Mark; Chantler, Paul D
2015-01-01
The metabolic syndrome (MetS) is associated with threefold increased risk of cardiovascular (CV) morbidity and mortality, which is partly due to a blunted CV reserve capacity, reflected by a reduced peak exercise left ventricular (LV) contractility and aerobic capacity and a blunted peak arterial-ventricular coupling. To date, no study has examined whether aerobic exercise training in MetS can reverse peak exercise CV dysfunction. Furthermore, examining how exercise training alters CV function in a group of individuals with MetS before the development of diabetes and/or overt CV disease can provide insights into whether some of the pathophysiological CV changes can be delayed/reversed, lowering their CV risk. The objective of this study was to examine the effects of 8 wk of aerobic exercise training in individuals with MetS on resting and peak exercise CV function. Twenty participants with MetS underwent either 8 wk of aerobic exercise training (MetS-ExT, n = 10) or remained sedentary (MetS-NonT, n = 10) during this period. Resting and peak exercise CV function was characterized using Doppler echocardiography and gas exchange. Exercise training did not alter resting LV diastolic or systolic function and arterial-ventricular coupling in MetS. In contrast, at peak exercise, an increase in LV contractility (40%, P < 0.01), cardiac output (28%, P < 0.05), and aerobic capacity (20%, P < 0.01), but a reduction in vascular resistance (30%, P < 0.05) and arterial-ventricular coupling (27%, P < 0.01), were noted in the MetS-ExT but not in the MetS-NonT group. Furthermore, an improvement in lifetime risk score was also noted in the MetS-ExT group. These findings have clinical importance because they provide insight that some of the pathophysiological changes associated with MetS can be improved and can lower the risk of CV disease.
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Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G; Stöhr, Eric J; Cotter, James D; Nio, Amanda Q X; Shave, Rob
2014-08-01
Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. Copyright © 2014 the American Physiological Society.
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Ainslie, Philip N.; Hughes, Michael G.; Stöhr, Eric J.; Cotter, James D.; Nio, Amanda Q. X.; Shave, Rob
2014-01-01
Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. PMID:24876358
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Stöhr, Eric J; González-Alonso, José; Pearson, James; Low, David A; Ali, Leena; Barker, Horace; Shave, Rob
2011-09-01
The purpose of this study was to determine whether the reduction in stroke volume (SV), previously shown to occur with dehydration and increases in internal body temperatures during prolonged exercise, is caused by a reduction in left ventricular (LV) function, as indicated by LV volumes, strain, and twist ("LV mechanics"). Eight healthy men [age: 20 ± 2, maximal oxygen uptake (VO₂max): 58 ± 7 ml·kg⁻¹·min⁻¹] completed two, 1-h bouts of cycling in the heat (35°C, 50% peak power) without fluid replacement, resulting in 2% and 3.5% dehydration, respectively. Conventional and two-dimensional speckle-tracking echocardiography was used to determine LV volumes, strain, and twist at rest and during one-legged knee-extensor exercise at baseline, both levels of dehydration, and following rehydration. Progressive dehydration caused a significant reduction in end-diastolic volume (EDV) and SV at rest and during one-legged knee-extensor exercise (rest: Δ-33 ± 14 and Δ-21 ± 14 ml, respectively; exercise: Δ-30 ± 10 and Δ-22 ± 9 ml, respectively, during 3.5% dehydration). In contrast to the marked decline in EDV and SV, systolic and diastolic LV mechanics were either maintained or even enhanced with dehydration at rest and during knee-extensor exercise. We conclude that dehydration-induced reductions in SV at rest and during exercise are the result of reduced LV filling, as reflected by the decline in EDV. The concomitant maintenance of LV mechanics suggests that the decrease in LV filling, and consequently ejection, is likely caused by the reduction in blood volume and/or diminished filling time rather than impaired LV function.
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Sardu, Celestino; Barbieri, Michelangela; Santamaria, Matteo; Giordano, Valerio; Sacra, Cosimo; Paolisso, Pasquale; Spirito, Alessandro; Marfella, Raffaele; Paolisso, Giuseppe; Rizzo, Maria Rosaria
2017-06-09
Type 2 diabetes mellitus (T2DM) is a multi factorial disease, affecting clinical outcomes in failing heart patients treated by cardiac resynchronization therapy with a defibrillator (CRT-d). One hundred and ninety-five T2DM patients received a CRT-d treatment. Randomly the study population received a CRT-d via multipolar left ventricle (LV) lead pacing (n 99, multipolar group), vs a CRT-d via bipolar LV pacing (n 96, bipolar group). These patients were followed by clinical, and instrumental assessment, and telemetric device control at follow up. In this study we evaluated, in a population of failing heart T2DM patients, cardiac deaths, all cause deaths, arrhythmic events, CRT-d responders rate, hospitalizations for HF worsening, phrenic nerve stimulation (PNS), and LV catheter dislodgment events (and re-intervention for LV catheter re-positioning), comparing multipolar CRT-d vs bipolar CRT-d group of patients at follow up. At follow up there was a statistical significant difference about atrial arrhythmic events [7 (7%) vs 16 (16.7%), p value 0.019], hospitalizations for HF worsening [15 (15.2% vs 24 (25%), p value 0.046], LV catheter dislodgments [1 (1%) vs 9 (9.4%), p value 0018], PNS [5 (5%) vs 18 (18.7%), p value 0.007], and LV re-positioning [1 (1%) vs 9 (9.4%), p value 0.018], comparing multipolar CRT-d vs bipolar CRT-d group of patients. Multipolar pacing was an independent predictor of all these events. CRT-d pacing via multipolar LV lead vs bipolar LV lead may reduce arrhythmic burden, hospitalization rate, PNS, LV catheters dislodgments, and re-interventions in T2DM failing heart patients. Clinical trial number NCT03095196.
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Biffi, Mauro; Exner, Derek V; Crossley, George H; Ramza, Brian; Coutu, Benoit; Tomassoni, Gery; Kranig, Wolfgang; Li, Shelby; Kristiansen, Nina; Voss, Frederik
2013-01-01
Unwanted phrenic nerve stimulation (PNS) has been reported in ∼1 in 4 patients undergoing left ventricular (LV) pacing. The occurrence of PNS over mid-term follow-up and the significance of PNS are less certain. Data from 1307 patients enrolled in pre-market studies of LV leads manufactured by Medtronic (models 4193 and 4195 unipolar, 4194, 4196, 4296, and 4396 bipolar) were pooled. Left ventricular lead location was recorded at implant using a common classification scheme. Phrenic nerve stimulation symptoms were either spontaneously reported or identified at scheduled follow-up visits. A PNS-related complication was defined as PNS resulting in invasive intervention or the termination of LV pacing. Average follow-up was 14.9 months (range 0.0-46.6). Phrenic nerve stimulation symptoms occurred in 169 patients (12.9%). Phrenic nerve stimulation-related complications occurred in 21 of 1307 patients (1.6%); 16 of 738 (2.2%) in the unipolar lead studies, and 5 of 569 (0.9%) in the bipolar lead studies (P = 0.08). Phrenic nerve stimulation was more frequent at middle-lateral/posterior, and apical LV sites (139/1010) vs. basal-posterior/lateral/anterior, and middle-anterior sites (20/297; P= 0.01). As compared with an anterior LV lead position, a lateral LV pacing site was associated with over a four-fold higher risk of PNS (P= 0.005) and an apical LV pacing site was associated with over six-fold higher risk of PNS (P= 0.001). Phrenic nerve stimulation occurred in 13% of patients undergoing LV lead placement and was more common at mid-lateral/posterior, and LV apical sites. Most cases (123/139; 88%) of PNS were mitigated via electrical reprogramming, without the need for invasive intervention.
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Motor unit potentials of the erector spinae muscle by concentric needle electromyography.
Posa, Andreas; Niśkiewicz, Izabela; Emmer, Alexander; Kluge, Yorck; Kornhuber, Malte E
2017-03-01
The needle electromyography (EMG) serves to supply additional information in patients with suspected neuromuscular disorders. We aimed to provide motor unit potential (MUP) data by concentric needle EMG in the erector spinae (ES) in comparison with biceps brachii (BB) and lateral vastus (LV). Electromyography MUP data ( n ) were obtained in ES (517), BB (539), and LV (627) in 32 healthy volunteers (16f). Motor unit potential data: amplitude (μV) 393 ± 174 (ES), 375 ± 162 (BB), and 577 ± 304 (LV); duration (ms) 10.4 ± 2.4 (ES), 10.1 ± 2.1 (BB), and 11.1 ± 2.3 (LV), area (μV × ms) 585 ± 327 (ES), 538 ± 267 (BB), and 881 ± 492 (LV); phase number 3.23 ± 0.94 (ES), 2.98 ± 0.76 (BB), and 3.19 ± 0.81 (LV); size index 0.60 ± 0.56 (ES), 0.51 ± 0.53 (BB), and 0.96 ± 0.55 (LV). LV displayed higher values ( p at least <.001) for MUP amplitude, duration, area, and size index as compared to both, BB and ES. Concentric needle EMG investigations in healthy adult human subjects revealed similar MUP parameters in the ES and BB muscles, while in the LV muscle MUP amplitude, duration, area, and size index were significantly larger. Different neuromuscular disorders display a predominant involvement of proximally located muscles such as truncal muscles. The present results given here may facilitate the diagnosis of neuromuscular disorders.
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Harms, Hendrik Johannes; Stubkjær Hansson, Nils Henrik; Tolbod, Lars Poulsen; Kim, Won Yong; Jakobsen, Steen; Bouchelouche, Kirsten; Wiggers, Henrik; Frøkiaer, Jørgen; Sörensen, Jens
2016-09-01
Dynamic cardiac PET is used to quantify molecular processes in vivo. However, measurements of left ventricular (LV) mass and volume require electrocardiogram-gated PET data. The aim of this study was to explore the feasibility of measuring LV geometry using nongated dynamic cardiac PET. Thirty-five patients with aortic-valve stenosis and 10 healthy controls underwent a 27-min (11)C-acetate PET/CT scan and cardiac MRI (CMR). The controls were scanned twice to assess repeatability. Parametric images of uptake rate K1 and the blood pool were generated from nongated dynamic data. Using software-based structure recognition, the LV wall was automatically segmented from K1 images to derive functional assessments of LV mass (mLV) and wall thickness. End-systolic and end-diastolic volumes were calculated using blood pool images and applied to obtain stroke volume and LV ejection fraction (LVEF). PET measurements were compared with CMR. High, linear correlations were found for LV mass (r = 0.95), end-systolic volume (r = 0.93), and end-diastolic volume (r = 0.90), and slightly lower correlations were found for stroke volume (r = 0.74), LVEF (r = 0.81), and thickness (r = 0.78). Bland-Altman analyses showed significant differences for mLV and thickness only and an overestimation for LVEF at lower values. Intra- and interobserver correlations were greater than 0.95 for all PET measurements. PET repeatability accuracy in the controls was comparable to CMR. LV mass and volume are accurately and automatically generated from dynamic (11)C-acetate PET without electrocardiogram gating. This method can be incorporated in a standard routine without any additional workload and can, in theory, be extended to other PET tracers. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Liu, Longjian; Nettleton, Jennifer A; Bertoni, Alain G; Bluemke, David A; Lima, João A; Szklo, Moyses
2009-08-01
Little is known about the relations between dietary patterns, metabolic dysfunction, and left ventricular (LV) function. The objective was to examine associations of dietary patterns with LV mass and function and to explore the potential role of metabolic dysfunction in the association between diet and LV function. Dietary patterns that maximally explained the variation in metabolic syndrome (MetSyn) components were derived by using reduced rank regression (RRR). LV mass, stroke volume, and LV ejection fraction (LVEF) were measured by magnetic resonance imaging. Associations between dietary pattern and LV indexes were analyzed cross-sectionally. A total of 4601 participants aged 45-84 y and free of clinical cardiovascular disease were studied. The primary RRR dietary pattern score was positively correlated with intake of foods with a high glycemic index, high-fat meats, cheeses, and processed foods and negatively correlated with low intakes of vegetables, soy, fruit, green and black tea, low-fat dairy desserts, seeds and nuts, and fish. Multivariate analyses showed that each 1-unit increase in the RRR dietary pattern score was associated with a 0.32-g/m(2) increase in LV mass/body surface area, a 0.43-mL/m(2) decrease in stroke volume/body surface area, and a 0.21% decrease in LVEF. The associations of the RRR dietary pattern score with LV mass and stroke indexes were attenuated and became nonsignificant after adjustment for all MetSyn components (P > 0.05). The results suggest that the RRR dietary pattern is significantly associated with unfavorable LV function, and this association might be mediated by metabolic dysfunction. Given the cross-sectional nature of our study, these results must be confirmed with the use of longitudinal data.
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Dovinová, Ima; Barancik, Miroslav; Zorad, Stefan; Gajdosechová, Lucia; Gresová, Linda; Cacanyiova, Sona; Kristek, Frantisek; Balis, Peter; Chan, Julie Y. H.
2013-01-01
PPARγ receptor plays an important role in oxidative stress response. Its agonists can influence vascular contractility in experimental hypertension. Our study was focused on the effects of a PPARγ agonist pioglitazone (PIO) on blood pressure regulation, vasoactivity of vessels, and redox-sensitive signaling at the central (brainstem, BS) and peripheral (left ventricle, LV) levels in young prehypertensive rats. 5-week-old SHR were treated either with PIO (10 mg/kg/day, 2 weeks) or with saline using gastric gavage. Administration of PIO significantly slowed down blood pressure increase and improved lipid profile and aortic relaxation after insulin stimulation. A significant increase in PPARγ expression was found only in BS, not in LV. PIO treatment did not influence NOS changes, but had tissue-dependent effect on SOD regulation and increased SOD activity, observed in LV. The treatment with PIO differentially affected also the levels of other intracellular signaling components: Akt kinase increased in the the BS, while β-catenin level was down-regulated in the BS and up-regulated in the LV. We found that the lowering of blood pressure in young SHR can be connected with insulin sensitivity of vessels and that β-catenin and SOD levels are important agents mediating PIO effects in the BS and LV. PMID:24454335
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Kim, Seong Hwan; Cho, Goo-Yeong; Baik, Inkyung; Lim, Sang Yup; Choi, Cheol Ung; Lim, Hong Euy; Kim, Eung Ju; Park, Chang Gyu; Park, Juri; Kim, Jinyoung; Shin, Chol
2011-02-01
Prehypertension is associated with increased cardiovascular morbidity and mortality. However, there are few population-based studies on the changes of cardiovascular structure and function that characterize prehypertension. The aim of this study was to assess whether prehypertension is associated with abnormalities of cardiovascular structure and function in the general Korean population. We analyzed the cross-sectional relationships between prehypertension and cardiovascular structure and function in a sample from the Korean Genome Epidemiology Study. A total of 1,671 individuals (54.5% women; mean age: 53 ± 6 years) without hypertension and diabetes mellitus were enrolled. Cardiovascular structure and function were assessed by conventional echocardiography, tissue Doppler imaging (TDI), carotid ultrasonography, and pulse wave velocity (PWV). The left ventricular (LV) mass index was significantly higher in subjects with prehypertension than in those with normotension (41 ± 8 g/m²·⁷ vs. 38 ± 7 g/m²·⁷, P < 0.001). LV diastolic parameters, such as the E/A ratio, TDI E(a) velocity, and E/E(a) ratio, were also impaired in subjects with prehypertension (all P < 0.001). Compared with normotension, prehypertension was characterized by a significantly higher common carotid artery intima-media thickness and a higher brachial-ankle PWV (all P < 0.001). These abnormalities of cardiovascular structure and function remained significant after adjustment for covariates. In this population-based cohort, we found that subtle alterations in cardiovascular structure and function were already present at the prehypertensive stage. Whether such subtle alterations convey an increased risk of cardiovascular events and whether the changes are reversible with treatment warrant further study.
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Loxosceles gaucho Venom-Induced Acute Kidney Injury – In Vivo and In Vitro Studies
Lucato, Rui V.; Abdulkader, Regina C. R. M.; Barbaro, Katia C.; Mendes, Glória E.; Castro, Isac; Baptista, Maria A. S. F.; Cury, Patrícia M.; Malheiros, Denise M. C.; Schor, Nestor; Yu, Luis; Burdmann, Emmanuel A.
2011-01-01
Background Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. Methodology/Principal Findings In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. Conclusions/Significance Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite. PMID:21655312
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Shen, W F; Roubin, G S; Fletcher, P J; Choong, C Y; Hutton, B F; Harris, P J; Kelly, D T
1985-02-01
The effects of upright and supine position on cardiac response to exercise were assessed by radionuclide ventriculography in 15 patients with moderate to severe aortic regurgitation (AR) and in 10 control subjects. In patients with AR, heart rate was higher during upright exercise, but systolic and diastolic blood pressure and left ventricular (LV) output were similar during both forms of exercise. LV stroke volume and end-diastolic volume were not altered during supine exercise. LV end-systolic volume increased and ejection fraction decreased during supine exercise, but both were unchanged during upright exercise. Of 15 patients, 5 in the upright and 12 in the supine position had an abnormal LV ejection fraction response to exercise (p less than 0.01). Right ventricular ejection fraction increased and regurgitant index decreased with both forms of exercise and was not significantly different between the 2 positions. Thus, posture is important in determining LV response to exercise in patients with moderate to severe AR.
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Lee, Lik Chuan; Zhihong, Zhang; Hinson, Andrew; Guccione, Julius M.
2013-01-01
Injection of Algisyl-LVR, a treatment under clinical development, is intended to treat patients with dilated cardiomyopathy. This treatment was recently used for the first time in patients who had symptomatic heart failure. In all patients, cardiac function of the left ventricle (LV) improved significantly, as manifested by consistent reduction of the LV volume and wall stress. Here we describe this novel treatment procedure and the methods used to quantify its effects on LV wall stress and function. Algisyl-LVR is a biopolymer gel consisting of Na+-Alginate and Ca2+-Alginate. The treatment procedure was carried out by mixing these two components and then combining them into one syringe for intramyocardial injections. This mixture was injected at 10 to 19 locations mid-way between the base and apex of the LV free wall in patients. Magnetic resonance imaging (MRI), together with mathematical modeling, was used to quantify the effects of this treatment in patients before treatment and at various time points during recovery. The epicardial and endocardial surfaces were first digitized from the MR images to reconstruct the LV geometry at end-systole and at end-diastole. Left ventricular cavity volumes were then measured from these reconstructed surfaces. Mathematical models of the LV were created from these MRI-reconstructed surfaces to calculate regional myofiber stress. Each LV model was constructed so that 1) it deforms according to a previously validated stress-strain relationship of the myocardium, and 2) the predicted LV cavity volume from these models matches the corresponding MRI-measured volume at end-diastole and end-systole. Diastolic filling was simulated by loading the LV endocardial surface with a prescribed end-diastolic pressure. Systolic contraction was simulated by concurrently loading the endocardial surface with a prescribed end-systolic pressure and adding active contraction in the myofiber direction. Regional myofiber stress at end-diastole and end-systole was computed from the deformed LV based on the stress-strain relationship. PMID:23608998
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Blood Pressure and Left Ventricular Remodeling Among American Style Football Players
Lin, Jeffrey; Wang, Francis; Weiner, Rory B.; DeLuca, James R.; Wasfy, Meagan M.; Berkstresser, Brant; Lewis, Gregory D.; Hutter, Adolph M.; Picard, Michael H.; Baggish, Aaron L.
2016-01-01
Objective To determine the relationships between American style football (ASF) participation, acquired left ventricular (LV) hypertrophy, and LV systolic function as assessed using contemporary echocardiographic parameters. Background Participation in ASF has been associated with the development of hypertension and LV hypertrophy. To what degree these processes impact LV function is unknown. Methods This is a prospective, longitudinal, cohort study evaluating NCAA Division I collegiate football athletes stratified by field position (linemen, n=30 vs. non-linemen, n=57) before and after a single competitive season with transthoracic echocardiography. LV systolic function was measured using complementary parameters of global longitudinal strain (GLS, 2D speckle-tracking) and ejection fraction (EF, 2D biplane). Results ASF participation was associated with field position-specific increases in systolic blood pressure (linemen Δ SBP = 10±8 mmHg vs. non-linemen Δ SBP = 3±7 mmHg, p<0.001) and an overall increase in incident LV hypertrophy (pre = 8% vs. post = 25%, p<0.05). Linemen who developed LV hypertrophy had concentric geometry (9/11, 82%) with decreased GLS (Δ = −1.1%, p<0.001) while non-linemen demonstrated eccentric LV hypertrophy (8/10, 80%) with increased GLS (Δ = +1.4%, p<0.001). In contrast, LV ejection fraction in the total cohort and when stratified by field position was not significantly affected by ASF participation. Among the total cohort, lineman field position, postseason weight, systolic blood pressure, average LV wall thickness, and relative wall thickness were all independent predictors of postseason GLS. Conclusions ASF participation at a lineman field position may lead to a form of sport-related myocardial remodeling that is pathologic rather than adaptive. Future study will be required to determine if targeted efforts to control blood pressure, minimize weight gain, and to include an element of aerobic conditioning in this subset of athletes may attenuate this process and translate into tangible downstream health benefits. PMID:27931524
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Weissler-Snir, Adaya; Kornowski, Ran; Sagie, Alexander; Vaknin-Assa, Hana; Perl, Leor; Porter, Avital; Lev, Eli; Assali, Abid
2014-11-15
Little is known regarding gender differences in left ventricular (LV) function after anterior wall ST-segment elevation myocardial infarction (STEMI), despite it being a major determinant of patients' morbidity and mortality. We therefore sought to investigate the impact of gender on LV function after primary percutaneous coronary intervention (PCI) for first anterior wall STEMI. Seven hundred eighty-nine consecutive patients (625 men) with first anterior STEMI were included in the analysis. All patients underwent an echocardiographic study within 48 hours of PCI. Women were older and more likely to have diabetes, hypertension, chronic renal failure, and a higher Killip score. Women had prolonged ischemic time, which was driven by prolonged symptom-to-presentation time (2.75 [interquartile range 1.5 to 4] vs 2 [interquartile range 1 to 3.5] hours, p = 0.005). A higher percentage of women had moderate or worse LV dysfunction (LV ejection fraction <40%; 61.6% vs 48%, p = 0.002). In a univariable analysis female gender was associated with moderate or worse LV function (p = 0.002). However, after accounting for variable baseline risk profiles between the 2 groups using multivariable and propensity score techniques, ischemic time >3.5 hours, leukocytosis, and pre-PCI Thrombolysis In Myocardial Infarction flow grade <2 were independent predictors of moderate or worse LV dysfunction, whereas female gender was not. Data on LV function recovery at 6 months, which were available for 45% of female and male patients with moderate or worse LV dysfunction early after PCI, showed no significant gender related difference in LV function recovery. In conclusion, women undergoing PCI for the first event of anterior STEMI demonstrate worse LV function than that of men, which might be partially attributed to delay in presentation. Hence greater efforts should be devoted to increasing women's awareness of cardiac symptoms during the prehospital course of STEMI. Copyright © 2014 Elsevier Inc. All rights reserved.
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Anisotropic Reinforcement of Acute Anteroapical Infarcts Improves Pump Function
Fomovsky, Gregory M.; Clark, Samantha A.; Parker, Katherine M.; Ailawadi, Gorav; Holmes, Jeffrey W.
2012-01-01
Background We hypothesize that a therapy that improves LV pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of left ventricular (LV) function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, while isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement. Methods and Results We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at Baseline, 45 minutes after coronary ligation (Ischemia), and 30 minutes later, following surgical reinforcement in the longitudinal direction (Anisotropic). Ischemia shifted the end-systolic pressure-volume relationship (ESPVR) and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure (EDP) by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function. Conclusions We conclude that anisotropic reinforcement is a promising new approach to improving LV function following a large myocardial infarction. PMID:22665716
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Liakopoulos, Oliver J; Ho, Jonathan K; Yezbick, Aaron B; Sanchez, Elizabeth; Singh, Vivek; Mahajan, Aman
2010-11-01
Augmentation of coronary perfusion may improve right ventricular (RV) failure following acute increases of RV afterload. We investigated whether intra-aortic balloon counterpulsation (IABP) can improve cardiac function by enhancing myocardial perfusion and reversing compromised biventricular interactions using a model of acute pressure overload. In 10 anesthetized pigs, RV failure was induced by pulmonary artery constriction and systemic hypertension strategies with IABP, phenylephrine (PE), or the combination of both were tested. Systemic and ventricular hemodynamics [cardiac index(CI), ventricular pressures, coronary driving pressures (CDP)] were measured and echocardiography was used to assess tricuspid valve regurgitation, septal positioning (eccentricity index (ECI)), and changes in ventricular and septal dimensions and function [myocardial performance index (MPI), peak longitudinal strain]. Pulmonary artery constriction resulted in doubling of RV systolic pressure (54 ± 4mm Hg), RV distension, severe TR (4+) with decreased RV function (strain: -33%; MPI: +56%), septal flattening (Wt%: -35%) and leftward septal shift (ECI:1.36), resulting in global hemodynamic deterioration (CI: -51%; SvO(2): -26%), and impaired CDP (-30%; P<0.05). IABP support alone failed to improve RV function despite higher CDP (+33%; P<0.05). Systemic hypertension by PE improved CDP (+70%), RV function (strain: +22%; MPI: -21%), septal positioning (ECI:1.12) and minimized TR, but LV dysfunction (strain: -25%; MPI: +31%) occurred after LV afterloading (P<0.05). With IABP, less PE (-41%) was needed to maintain hypertension and CDP was further augmented (+25%). IABP resulted in LV unloading and restored LV function, and increased CI (+46%) and SvO(2) (+29%; P<0.05). IABP with minimal vasopressors augments myocardial perfusion pressure and optimizes RV function after pressure-induced failure. Copyright © 2010 Elsevier Inc. All rights reserved.
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Hwang, Su Jin; Lee, Hye Won; Kim, Hye Ree; Song, Hye Jin; Lee, Dong Heon; Lee, Hong; Shin, Chang Hoon; Joung, Je-Gun; Kim, Duk-Hwan; Joo, Kyeung Min; Kim, Hyeon Ho
2015-08-21
Despite great efforts to improve survival rates, the prognosis of lung cancer patients is still very poor, mainly due to high invasiveness. We developed brain metastatic PC14PE6/LvBr4 cells through intracardiac injection of lung adenocarcinoma PC14PE6 cells. Western blot and RT-qPCR analyses revealed that PC14PE6/LvBr4 cells had mesenchymal characteristics and higher invasiveness than PC14PE6 cells. We found that cyclin D1 was upregulated, miR-95-3p was inversely downregulated, and pri-miR-95 and its host gene, ABLIM2, were consistently decreased in PC14PE6/LvBr4 cells. MiR-95-3p suppressed cyclin D1 expression through direct binding to the 3' UTR of cyclin D1 mRNA and suppressed invasiveness, proliferation, and clonogenicity of PC14PE6/LvBr4 cells. Ectopic cyclin D1 reversed miR-95-3p-mediated inhibition of invasiveness and clonogenicity, demonstrating cyclin D1 downregulation is involved in function of miR-95-3p. Using bioluminescence imaging, we found that miR-95-3p suppressed orthotopic tumorigenicity and brain metastasis in vivo and increased overall survival and brain metastasis-free survival. Consistent with in vitro metastatic cells, the levels of miR-95-3p, pri-miR-95, and ABLIM2 mRNA were decreased in brain metastatic tissues compared with lung cancer tissues and higher cyclin D1 expression was involved in poor prognosis. Taken together, our results demonstrate that miR-95-3p is a potential therapeutic target for brain metastasis of lung adenocarcinoma cells.
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Juneman, Elizabeth B; Saleh, Laith; Lancaster, Jordan J; Thai, Hoang M; Markham, Bruce; Goldman, Steven
2012-09-01
Poloxamer-188 (P-188) is a biological membrane sealant that prevents the unregulated entry of Ca into cardiomyocytes and has been shown to have the ability to act as a membrane-repair agent in isolated cardiac myocytes. The purpose of this study was to determine if treatment with P-188 would improve left ventricular (LV) function in a rat chronic heart failure (CHF) model. We ligated the left coronary artery of adult male Sprague-Dawley rats to induce a myocardial infarction (MI). The rats were allowed to recover for 8 weeks until stable CHF was present and treated with a range of P-188 doses [1.5 mg/kg (N = 6), 4.6 mg/kg (N = 11), 15.3 mg/kg (N = 11), and 460 mg/kg (N = 6)] delivered via 30 minutes of intravenous infusion. The rats were randomized to study groups: control, 2 hours, 24 hours, 48 hours, 1 week, and 2 weeks posttreatment (N = 8 in each group). Two weeks after high dose (460 mg/kg) administration, P-188 improved (P < 0.05) left ventricular ejection fraction from 34% to 51%, which persisted over 38 hours and decreased (P < 0.05) LV end systolic diameter from 0.9 ± 0.07 to 0.6 ± 0.08 cm, in the rats with CHF. There was no statistical change in hemodynamics. Additionally, P-188 reduced (P < 0.05) circulating troponin levels 2 weeks after treatment. Treatment with P-188 improves the LV function and partially reverses maladaptive LV remodeling in rats with moderate CHF after MI. These data introduce the idea of using a biological membrane sealant as a new approach to treating CHF after MI.
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Selective Packaging of Host tRNA's by Murine Leukemia Virus Particles Does Not Require Genomic RNA
Levin, Judith G.; Seidman, J. G.
1979-01-01
The 4S RNA contained in RNA tumor virus particles consists of a selected population of host tRNA's. However, the mechanism by which virions select host tRNA's has not been elucidated. We have considered a model which specifies that 35S genomic RNA determines which tRNA's are to be encapsidated as well as the relative amounts of these tRNA's within the virion. The model was tested by comparing the free 4S RNA composition of normal murine leukemia virus (MuLV) particles and noninfectious virions from actinomycin D (ActD)-treated cells, which are deficient in genomic RNA (ActD virions). Viral 4S RNA was analyzed by two-dimensional polyacrylamide gel electrophoresis. Surprisingly, the patterns obtained for control and ActD 4S RNA were identical to each other and were clearly distinct from the cell 4S RNA pattern. The viral patterns had three prominent areas of radioactivity. One of the spots was identified on the basis of its oligonucleotide fingerprint as tRNA Pro, the primer for MuLV RNA-directed DNA synthesis. These results were obtained with two different MuLV strains, AKR and Moloney, each grown in SC-1 cells. The demonstration that ActD virions contain primer tRNA and in general exhibit the characteristic MuLV tRNA pattern rather than the complete representation of cell 4S RNA leads to the conclusion that genomic RNA is not the major determinant in selective packaging of host tRNA's. A possible role for one or more viral proteins, including reverse transcriptase, is suggested. Images PMID:219227
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Chang, Yi-Yao; Lee, Hsiu-Hao; Hung, Chi-Sheng; Wu, Xue-Ming; Lee, Jen-Kuang; Wang, Shuo-Meng; Liao, Min-Tsun; Chen, Ying-Hsien; Wu, Vin-Cent; Wu, Kwan-Dun; Lin, Yen-Hung
2014-09-01
To investigate the association between aldosterone and cardiac diastolic dysfunction. We prospectively enrolled 20 patients with primary aldosteronism (PA) and 22 patients with essential hypertension (EH). Plasma aldosterone concentration, plasma renin activity, and 24-h urine aldosterone level were measured. Echocardiography, including tissue Doppler image recordings, was performed. PA patients had a significantly higher left ventricular (LV) mass index and worse LV diastolic function than those in EH patients. Among various measures of aldosterone, log-transformed 24-h urine aldosterone level had the most consistent correlation with diastolic function. Aldosterone is strongly associated with LV diastolic dysfunction. Twenty-four hour urine aldosterone is a good indicator to evaluate the impact of aldosterone on LV diastolic function. Copyright © 2014. Published by Elsevier Inc.
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NASA Astrophysics Data System (ADS)
Kranzbühler, Benedikt; Gross, Oliver; Fankhauser, Christian D.; Hefermehl, Lukas J.; Poyet, Cédric; Largo, Remo; Müntener, Michael; Seifert, Hans-Helge; Zimmermann, Matthias; Sulser, Tullio; Müller, Alexander; Hermanns, Thomas
2012-02-01
Introduction and objectives: Greenlight laser vaporization (LV) of the prostate is characterized by simultaneous vaporization and coagulation of prostatic tissue resulting in tissue ablation together with excellent hemostasis during the procedure. It has been reported that bipolar plasma vaporization (BPV) of the prostate might be an alternative for LV. So far, it has not been shown that BPV is as effective as LV in terms of tissue ablation or hemostasis. We performed transrectal three-dimensional ultrasound investigations to compare the efficiency of tissue ablation between LV and BPV. Methods: Between 11.2009 and 5.2011, 50 patients underwent pure BPV in our institution. These patients were matched with regard to the pre-operative prostate volume to 50 LV patients from our existing 3D-volumetry-database. Transrectal 3D ultrasound and planimetric volumetry of the prostate were performed pre-operatively, after catheter removal, 6 weeks and 6 months. Results: Median pre-operative prostate volume was not significantly different between the two groups (45.3ml vs. 45.4ml; p=1.0). After catheter removal, median absolute volume reduction (BPV 12.4ml, LV 6.55ml) as well as relative volume reduction (27.8% vs. 16.4%) were significantly higher in the BPV group (p<0.001). After six weeks (42.9% vs. 33.3%) and six months (47.2% vs. 39.7%), relative volume reduction remained significantly higher in the BPV group (p<0.001). Absolute volume reduction was non-significantly higher in the BPV group after six weeks (18.4ml, 13.8ml; p=0.051) and six months (20.8ml, 18ml; p=0.3). Clinical outcome parameters improved significantly in both groups without relevant differences between the groups. Conclusions: Both vaporization techniques result in efficient tissue ablation with initial prostatic swelling. BPV seems to be superior due to a higher relative volume reduction. This difference had no clinical impact after a follow-up of 6M.
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Karur, Gauri R; Robison, Sean; Iwanochko, Robert M; Morel, Chantal F; Crean, Andrew M; Thavendiranathan, Paaladinesh; Nguyen, Elsie T; Mathur, Shobhit; Wasim, Syed; Hanneman, Kate
2018-04-24
Purpose To compare left ventricular (LV) and right ventricular (RV) 3.0-T cardiac magnetic resonance (MR) imaging T1 values in Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM) and evaluate the diagnostic value of native T1 values beyond age, sex, and conventional imaging features. Materials and Methods For this prospective study, 30 patients with gene-positive AFD (37% male; mean age ± standard deviation, 45.0 years ± 14.1) and 30 patients with HCM (57% male; mean age, 49.3 years ± 13.5) were prospectively recruited between June 2016 and September 2017 to undergo cardiac MR imaging T1 mapping with a modified Look-Locker inversion recovery (MOLLI) acquisition scheme at 3.0 T (repetition time msec/echo time msec, 280/1.12; section thickness, 8 mm). LV and RV T1 values were evaluated. Statistical analysis included independent samples t test, receiver operating characteristic curve analysis, multivariable logistic regression, and likelihood ratio test. Results Septal LV, global LV, and RV native T1 values were significantly lower in AFD compared with those in HCM (1161 msec ± 47 vs 1296 msec ± 55, respectively [P < .001]; 1192 msec ± 52 vs 1268 msec ± 55 [P < .001]; and 1221 msec ± 54 vs 1271 msec ± 37 [P = .001], respectively). A septal LV native T1 cutoff point of 1220 msec or lower distinguished AFD from HCM with sensitivity of 97%, specificity of 93%, and accuracy of 95%. Septal LV native T1 values differentiated AFD from HCM after adjustment for age, sex, and conventional imaging features (odds ratio, 0.94; 95% confidence interval: 0.91, 0.98; P = < .001). In a nested logistic regression model with age, sex, and conventional imaging features, model fit was significantly improved by the addition of septal LV native T1 values (χ 2 [df = 1] = 33.4; P < .001). Conclusion Cardiac MR imaging native T1 values at 3.0 T are significantly lower in patients with AFD compared with those with HCM and provide independent and incremental diagnostic value beyond age, sex, and conventional imaging features. © RSNA, 2018.
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Qin, Yanjun; Yu, Yueqing; Dong, Hua; Bian, Xiaohua; Guo, Xuan; Dong, Shimin
2012-01-01
Objective: To determine the role of microRNA 21(miR-21) on left ventricular remodeling of rat heart with ischemia-reperfusion (I/R) injury and to investigate the underlying mechanism of miR-21 mediated myocardium protection. Methods: Rats were randomly divided into three groups: an I/R model group with Ad-GFP (Ad-GFP group), an I/R model group with Ad-miR-21 (Ad-miR-21 group) and a sham-surgery group. Changes in hemodynamic parameters were recorded at 1 week after I/R. Histological diagnosis was achieved by hematoxylin and eosin (H&E). Left ventricular (LV) dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells were measured. Primary cultures of neonatal rat cardiac ventricular myocytes were performed and cell ischemic injury was induced by hypoxia in a serum- and glucose-free medium, and reoxygenation (H/R).MiR-21 inhibitor and pre-miR-21 were respectively added to the culture medium for the miR-21 knockdown and for the miR-21 up-regulation. qRT-PCR was used to determine the miR-21 levels in cultured cells. Flow cytometry was performed to examine the cell apoptosis. Results: In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells all significantly decreased compared with the Ad-GFP group. At 1 week after I/R, the Ad-miR-21 significantly improved LVSP, LV +dp/dtmax, LV − dp/dtmin, and decreased heart rate (HR) and LVEDP compared with the Ad-GFP group. Compared with the Ad-GFP, the cell apoptotic rate significantly decreased in the Ad-miR-21 group. The miR-21 inhibitor exacerbated cardiac myocyte apoptosis and the pre-miR-21 decreased hypoxia/reoxygenation- induced cardiac myocyte apoptosis. Conclusions: Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury. PMID:22859901
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Helfer-Hungerbuehler, A Katrin; Widmer, Stefan; Kessler, Yvonne; Riond, Barbara; Boretti, Felicitas S; Grest, Paula; Lutz, Hans; Hofmann-Lehmann, Regina
2015-02-02
It is a remarkable feature for a retrovirus that an infection with feline leukemia virus (FeLV) can result in various outcomes. Whereas some cats contain the infection and show a regressive course, others stay viremic and succumb to the infection within a few years. We hypothesized, that differences in the infection outcome might be causally linked to the viral RNA and provirus loads within the host and these loads therefore may give additional insight into the pathogenesis of the virus. Thus, the goals of the present study were to follow-up on experimentally infected cats and investigate tissues from cats with different infection outcomes using sensitive, specific TaqMan real-time PCR and reverse transcriptase (RT)-PCR. Nineteen experimentally FeLV-A/Glasgow-1-infected cats were categorized into having regressive, progressive or reactivated FeLV infection according to follow-up of FeLV p27 antigen detection in the blood. Remarkably, regressively infected cats showed detectable provirus and viral RNA loads in almost all of the 27 tested tissues, even many years after virus exposure. Moreover, some regressively infected cats reactivated the infection, and these cats had intermediate to high viral RNA and provirus tissue loads. The highest loads were found in viremic cats, independent of their health status. Tissues that represented sites of virus replication and shedding revealed the highest viral RNA and provirus loads, while the lowest loads were present in muscle and nerve tissues. A supplementary analysis of 20 experimentally infected cats with progressive infection revealed a median survival time of 3.1 years (range from 0.6 to 6.5 years); ∼70% (n=14) of these cats developed lymphoma, while leukemia and non-regenerative anemia were observed less frequently. Our results demonstrate that the different infection outcomes are associated with differences in viral RNA and provirus tissue loads. Remarkably, no complete clearance of FeLV viral RNA or provirus was detected in cats with regressive infection, even up to 12 years after exposure. In several cases FeLV reactivation could be observed. Thus, retroviruses integrated as provirus into the host's genome, could not be eliminated completely by the host and maintained their full potential for replication and reactivation. Copyright © 2014 Elsevier B.V. All rights reserved.
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Ceriani, Luca; Ruberto, Teresa; Delaloye, Angelika Bischof; Prior, John O; Giovanella, Luca
2010-03-01
The purposes of this study were to characterize the performance of a 3-dimensional (3D) ordered-subset expectation maximization (OSEM) algorithm in the quantification of left ventricular (LV) function with (99m)Tc-labeled agent gated SPECT (G-SPECT), the QGS program, and a beating-heart phantom and to optimize the reconstruction parameters for clinical applications. A G-SPECT image of a dynamic heart phantom simulating the beating left ventricle was acquired. The exact volumes of the phantom were known and were as follows: end-diastolic volume (EDV) of 112 mL, end-systolic volume (ESV) of 37 mL, and stroke volume (SV) of 75 mL; these volumes produced an LV ejection fraction (LVEF) of 67%. Tomographic reconstructions were obtained after 10-20 iterations (I) with 4, 8, and 16 subsets (S) at full width at half maximum (FWHM) gaussian postprocessing filter cutoff values of 8-15 mm. The QGS program was used for quantitative measurements. Measured values ranged from 72 to 92 mL for EDV, from 18 to 32 mL for ESV, and from 54 to 63 mL for SV, and the calculated LVEF ranged from 65% to 76%. Overall, the combination of 10 I, 8 S, and a cutoff filter value of 10 mm produced the most accurate results. The plot of the measures with respect to the expectation maximization-equivalent iterations (I x S product) revealed a bell-shaped curve for the LV volumes and a reverse distribution for the LVEF, with the best results in the intermediate range. In particular, FWHM cutoff values exceeding 10 mm affected the estimation of the LV volumes. The QGS program is able to correctly calculate the LVEF when used in association with an optimized 3D OSEM algorithm (8 S, 10 I, and FWHM of 10 mm) but underestimates the LV volumes. However, various combinations of technical parameters, including a limited range of I and S (80-160 expectation maximization-equivalent iterations) and low cutoff values (< or =10 mm) for the gaussian postprocessing filter, produced results with similar accuracies and without clinically relevant differences in the LV volumes and the estimated LVEF.
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Liang, Yanchun; Yu, Haibo; Zhou, Weiwei; Xu, Guoqing; Sun, Y I; Liu, Rong; Wang, Zulu; Han, Yaling
2015-12-01
Electrophysiological mapping (EPM) in coronary sinus (CS) branches is feasible for guiding LV lead placement to the optimal, latest activated site at cardiac resynchronization therapy (CRT) procedures. However, whether this procedure optimizes the response to CRT has not been demonstrated. This study was to evaluate effects of targeting LV lead at the latest activated site guided by EPM during CRT. Seventy-six consecutive patients with advanced heart failure who were referred for CRT were divided into mapping (MG) and control groups (CG). In MG, the LV lead, also used as a mapping bipolar electrode, was placed at the latest activated site determined by EPM in CS branches. In CG, conventional CRT procedure was performed. Patients were followed for 6 months after CRT. Baseline characteristics were comparable between the 2 groups. In MG (n = 29), EPM was successfully performed in 85 of 91 CS branches during CRT. A LV lead was successfully placed at the latest activated site guided by EPM in 27 (93.1%) patients. Compared with CG (n = 47), MG had a significantly higher rate (86.2% vs. 63.8%, P = 0.039) of response (>15% reduction in LV end-systolic volume) to CRT, a higher percentage of patients with clinical improvement of ≥2 NYHA functional classes (72.4% vs. 44.7%, P = 0.032), and a shorter QRS duration (P = 0.004). LV lead placed at the latest activated site guided by EPM resulted in a significantly greater CRT response, and a shorter QRS duration. © 2015 Wiley Periodicals, Inc.
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Sun, Dianjianyi; Wang, Tiange; Heianza, Yoriko; Lv, Jun; Han, Liyuan; Rabito, Felicia; Kelly, Tanika; Li, Shengxu; He, Jiang; Bazzano, Lydia; Chen, Wei; Qi, Lu
2017-07-01
This study aimed to examine whether a history of asthma from childhood is associated with left ventricular (LV) mass in adulthood. Asthma has been related to various cardiovascular risk factors affecting LV hypertrophy. The authors saw a need for a prospective study to analyze the relationship between a history of asthma from childhood and markers of LV mass among asymptomatic young adults. Prospective analyses were performed among 1,118 Bogalusa Heart Study participants (average age at follow-up 36.7 ± 5.1 years), with a baseline history of self-reported asthma collected since childhood (average age at baseline 26.8 ± 10.1 years). LV mass (g) was assessed using 2-dimensional guided M-mode echocardiography and was indexed for body height (m 2.7 ) as LV mass index (LVMI; g/m 2.7 ). A multivariate linear mixed model was fitted for the repeated measures. After an average of 10.4 ± 7.5 years of follow-up, participants with a history of asthma from childhood had a greater LV mass (167.6 vs. 156.9; p = 0.01) and LVMI (40.7 vs. 37.7; p < 0.01) with adjustment for age, sex, race, smoking status, antihypertensive medication, heart rate, and systolic blood pressure (SBP). The difference of LVMI between group with asthma and the group without asthma remained significant after additional adjustment for body mass index (39.0 vs. 37.1; p = 0.03) and high-sensitivity C-reactive protein (38.4 vs. 36.6; p = 0.04). In addition, the authors found significant interactions between SBP and asthma on LV mass and LVMI (p for interaction <0.01, respectively). The associations between asthma and LV measures appeared to be stronger among pre-hypertensive and hypertensive participants (SBP ≥130 mm Hg) compared with participants with normal SBP (<130 mm Hg) (regression coefficient: 39.5 vs. 2.3 for LV mass and 9.0 vs. 0.9 for LVMI). The findings of this study indicate that a history of asthma is associated with higher LVMI, and this association is stronger among participants with pre-hypertension and hypertension. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Association of Cardiac Troponin T With Left Ventricular Structure and Function in CKD
Mishra, Rakesh K.; Li, Yongmei; DeFilippi, Christopher; Fischer, Michael J.; Yang, Wei; Keane, Martin; Chen, Jing; He, Jiang; Kallem, Radhakrishna; Horwitz, Ed; Rafey, Mohammad; Raj, Dominic S.; Go, Alan S.; Shlipak, Michael G.
2013-01-01
Background Serum cardiac troponin T (cTnT) is associated with increased risk of heart failure and cardiovascular death in several population settings. We evaluated associations of cTnT with cardiac structural and functional abnormalities in a cohort of chronic kidney disease (CKD) patients without heart failure. Study Design Cross-sectional. Setting & Participants Chronic Renal Insufficiency Cohort (CRIC; N= 3,243) Predictor The primary predictor was cTnT. Secondary predictors included demographic and clinical characteristics, hemoglobin level, high-sensitivity C-reactive protein, and estimated glomerular filtration rate using cystatin C. Outcomes Echocardiography was used to determine left ventricular (LV) mass and LV systolic and diastolic function. Measurements Circulating cTnT was measured in stored sera using the highly sensitive assay. Logistic and linear regression models were used to examine associations of cTnT with each echocardiographic outcome. Results cTnT was detectable in 2,735 (84%) persons; the median was 13.3 (IQR, 7.7–23.8) pg/mL. Compared with undetectable cTnT (<3.0 pg/mL), the highest quartile (23.9 – 738.7 pg/mL) was associated with approximately two times as likely to experience LV hypertrophy (OR, 2.43; 95% CI, 1.44–4.09) in the fully adjusted model. cTnT had a more modest association with LV systolic dysfunction; as a log-linear variable, a significant association was present in the fully adjusted model (OR of 1.4 [95% CI, 1.1–1.7] per 1-log unit; p<0.01). There was no significant independent association between cTnT and LV diastolic dysfunction. When evaluated as a screening test, cTnT functioned only modestly for LV hypertrophy and concentric hypertrophy detection (area under the curve, 0.64 for both) with weaker areas under the curve for the other outcomes. Limitations The presence of coronary artery disease was not formally assessed using either noninvasive or angiographic techniques in this study. Conclusions In this large CKD cohort without heart failure, detectable cTnT had a strong association with LV hypertrophy, a more modest association with LV systolic dysfunction, and no association with diastolic dysfunction. These findings indicate that circulating cTnT levels in CKD are predominantly an indicator of pathological LV hypertrophy. PMID:23291148
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Association of cardiac troponin T with left ventricular structure and function in CKD.
Mishra, Rakesh K; Li, Yongmei; DeFilippi, Christopher; Fischer, Michael J; Yang, Wei; Keane, Martin; Chen, Jing; He, Jiang; Kallem, Radhakrishna; Horwitz, Edward J; Rafey, Mohammad; Raj, Dominic S; Go, Alan S; Shlipak, Michael G
2013-05-01
Serum cardiac troponin T (cTnT) is associated with increased risk of heart failure and cardiovascular death in several population settings. We evaluated associations of cTnT levels with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease (CKD) without heart failure. Cross-sectional. Chronic Renal Insufficiency Cohort (CRIC; N=3,243). The primary predictor was cTnT level. Secondary predictors included demographic and clinical characteristics, hemoglobin level, high-sensitivity C-reactive protein level, and estimated glomerular filtration rate using cystatin C. Echocardiography was used to determine left ventricular (LV) mass and LV systolic and diastolic function. Circulating cTnT was measured in stored sera using the highly sensitive assay. Logistic and linear regression models were used to examine associations of cTnT level with each echocardiographic outcome. cTnT was detectable in 2,735 (84%) persons; median level was 13.3 (IQR, 7.7-23.8) pg/mL. Compared with undetectable cTnT (<3.0 pg/mL), the highest quartile (23.9-738.7 pg/mL) was approximately 2 times as likely to have LV hypertrophy (OR, 2.43; 95% CI, 1.44-4.09) in the fully adjusted model. cTnT level had a more modest association with LV systolic dysfunction; as a log-linear variable, a significant association was present in the fully adjusted model (OR of 1.4 [95% CI, 1.2-1.7] per 1-log unit; P < 0.001). There was no significant independent association between cTnT level and LV diastolic dysfunction. When evaluated as a screening test, cTnT level functioned only modestly for LV hypertrophy and concentric hypertrophy detection (area under the curve, 0.64 for both), with weaker areas under the curve for the other outcomes. The presence of coronary artery disease was not formally assessed using either noninvasive or angiographic techniques in this study. In this large CKD cohort without heart failure, detectable cTnT had a strong association with LV hypertrophy, a more modest association with LV systolic dysfunction, and no association with diastolic dysfunction. These findings indicate that circulating cTnT levels in patients with CKD are predominantly an indicator of pathologic LV hypertrophy. Published by Elsevier Inc.
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2014-01-01
Background Insulin resistance, as a key mediator of metabolic syndrome, is thought to be associated with pathogenesis of calcific aortic valve disease and altered left ventricular (LV) function and structure. However, in patients with aortic valve sclerosis (AVS), the association between insulin resistance and subclinical impairment of LV function is not fully elucidated. Methods We studied 57 patients (mean age 70 ± 8 years, 22 women) with asymptomatic AVS but normal LV ejection fraction in echocardiography. LV longitudinal and circumferential strain and strain rate was analyzed using two-dimensional speckle tracking echocardiography. Patients with uncontrolled hypertension and diabetes mellitus, chronic kidney disease, and concomitant coronary artery disease were excluded. They were divided into the insulin-resistant group (AVS+IR; N = 28) and no insulin-resistant group (AVS-IR; N = 29) according to the median value of homeostatic model assessment index. Computed tomography scans were also performed to measure the aortic valve calcium score and the visceral adipose tissue (VAT) area. In addition, age- and sex- adjusted 28 control subjects were recruited for the comparison. Results There were no significant differences in LV ejection fraction or mass index among the groups. The AVS+IR group had a higher aortic valve calcium score (median 94 versus 21, P = 0.022) and a larger VAT area (113 ± 42 cm2 versus 77 ± 38 cm2, P = 0.001) than the AVS-IR group. Notably, LV global longitudinal strain, strain rate (SR), and early diastolic SR were significantly lower in the AVS+IR group than in the AVS-IR group and in control subjects (strain: -16.2 ± 1.6% versus -17.2 ± 1.2% and -18.9 ± 0.8%; SR: -1.18 ± 0.26 s-1 versus -1.32 ± 0.21 s-1 and -1.52 ± 0.08 s-1; early diastolic SR: -1.09 ± 0.23 s-1 versus -1.23 ± 0.18 s-1 and -1.35 ± 0.12 s-1; P < 0.05 for all comparison), whereas circumferential function were not significantly different. Multiple linear regression analyses revealed insulin resistance as an independent determinant of LV longitudinal strain (P = 0.017), SR (P = 0.047), and early diastolic SR (P = 0.049) regardless of LV mass index or VAT area. Conclusions Insulin resistance is a powerful independent predictor of subclinical LV dysfunction regardless of concomitant visceral obesity and LV hypertrophy. Thus, it may be a novel therapeutic target to prevent subsequent heart failure in patients with AVS. PMID:24767168
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Skrzypek, Agnieszka; Nessler, Jadwiga
2015-01-01
Measurement of oxygen uptake at the maximal exercise (VO2max) in the cardio-pulmonary exercise test provides the most reliable information about exertion tolerance. Establishment of VO2peak, VE/CO2 and AT value in the early diagnosis of asymptomatic heart dysfunction in patients with coronary disease (CAD) and prognosis during 2-years observation. The study population: 57 patients (35 M) with CAD, without any signs or symptoms of heart dysfunction, without any features of myocardial infarction, in the age 51.08 +/- 4.01. The analysis was performed twice: in the beginning and after 2-years observation. Physical examinations, echocardiographic parameters [(assessment of systolic and diastolic dysfunction of the left ventricle (LV)] and spiroergometric parameters (VO2peak, VE/CO2 at AT). On the basis of echocardiographic examination, there were created groups of patients: Group A--the patients with normal LV function (n=32; 56.2%; 23 M); Group B--the patients with diastolic heart dysfunction (n=22; 38.6%; 10 M); Group A--32 patients in the age of 50.9 +/- 4, 23 men. Values of VO2pe ak :28.8 +/- 6 ml/kg/min, VE/CO2 28.8 +/- 4.9 and AT 18 +/- 2.5. Group B--the patients with diastolic heart dysfunction: 22 (39%) patients; 10 men, in the age of 51.2 +/- 4.3. Values of VO2peak: 26 +/- 3.4 mi/ kg/min, VE/CO2 31.2 +/- 5.1 and AT 16 +/- 2.5. In the beginning of the study was established significantly differences between anaerobic threshold and degree of heart dysfunction (p=0.039). (1) There was observed that VO2 A and VE/CO2 depended on filling LV profile LV and also of systolic LV function. Anaerobic threshold significantly depended on LV filling pattern. (2) In asymptomatic patients with LV diastolic dysfunction and VO2peak < or = 18.4 ml/kg/min was observed progression of LV diastolic dysfunction during two years.
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Wergedal, Jon E.; Stiffel, Virginia; Lau, Kin-Hing William
2014-01-01
This study sought to determine if direct application of the lentiviral (LV)-cyclooxygenase 2 (COX2) vector to the tendon-bone interface would promote osteointegration of the tendon graft in a rat model of biceps tenodesis. The LV-COX2 gene transfer strategy was chosen for investigation because a similar COX2 gene transfer strategy promoted bony bridging of the fracture gap during bone repair, which involves similar histologic transitions that occur in osteointegration. Briefly, a 1.14-mm diameter tunnel was drilled in the mid-groove of the humerus of adult Fischer 344 rats. The LV-COX2 or βgal control vector was applied directly into the bone tunnel and onto the end of the tendon graft, which was then pulled into the bone tunnel. A poly-L-lactide pin was press-fitted into the tunnel as interference fixation. Animals were sacrificed at 3, 5, or 8 weeks for histology analysis of osteointegration. The LV-COX2 gene transfer strategy enhanced neo-chondrogenesis at the tendon-bone interface but with only marginal effect on de novo bone formation. The tendon-bone interface of the LV-COX2-treated tenodesis showed the well-defined tendon-to-fibrocartilage-to-bone histologic transitions that are indicative of osteointegration of the tendon graft. The LV-COX2 in vivo gene transfer strategy also significantly enhanced angiogenesis at the tendon-bone interface. To determine if the increased osteointegration was translated into an improved pull-out mechanical strength property, the pull-out tensile strength of the LV-COX2-treated tendon grafts was determined with a pull-out mechanical testing assay. The LV-COX2 strategy yielded a significant improvement in the return of the pull-out strength of the tendon graft after 8 weeks. In conclusion, the COX2-based in vivo gene transfer strategy enhanced angiogenesis, osteointegration and improved return of the pull-out strength of the tendon graft. Thus, this strategy has great potential to be developed into an effective therapy to promote tendon-to-bone healing after tenodesis or related surgeries. PMID:24848992
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Cardiac atrophy in women following bed rest.
Dorfman, Todd A; Levine, Benjamin D; Tillery, Tommy; Peshock, Ronald M; Hastings, Jeff L; Schneider, Suzanne M; Macias, Brandon R; Biolo, Gianni; Hargens, Alan R
2007-07-01
Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 +/- 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6 degrees head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n = 8), or 2) protein (0.45 g x kg(-1) x day(-1) increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation (n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 +/- 26 to 77 +/- 25 ml; P = 0.03) and RV volumes (104 +/- 33 to 86 +/- 25 ml; P = 0.02), LV (2.2 +/- 0.2 to 2.0 +/- 0.2 g/kg; P = 0.003) and RV masses (0.8 +/- 0.1 to 0.6 +/- 0.1 g/kg; P < 0.001), and the length of the major axis of the LV (90 +/- 6 to 84 +/- 7 mm. P < 0.001), similar to what has been observed previously in men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645-653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 +/- 0.4 to 2.3 +/- 0.3 g/kg; P < 0.001) and RV masses (0.7 +/- 0.1 to 0.8 +/- 0.2 g/kg; P = 0.002), as well as mean wall thickness (9 +/- 2 to 11 +/- 1 mm; P = 0.02). The interaction between sedentary and exercise LV and RV masses was highly significant (P < 0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103 +/- 14 to 80 +/- 16 ml; P = 0.02) and major-axis length (91 +/- 5 to 88 +/- 7 mm; P = 0.003). All subjects lost an equivalent amount of body mass (3.4 +/- 0.2 kg control; 3.1 +/- 0.04 kg exercise; 2.8 +/- 0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ye, Lusi; Department of Rheumatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325015; Jiang, Ying
Objective: The farnesoid-X-receptor (FXR) is a metabolic nuclear receptor superfamily member that is highly expressed in enterohepatic tissue and is also expressed in the cardiovascular system. Multiple nuclear receptors, including FXR, play a pivotal role in cardiovascular disease (CVD). Pulmonary arterial hypertension (PAH) is an untreatable cardiovascular system disease that leads to right heart failure (RHF). However, the potential physiological/pathological roles of FXR in PAH and RHF are unknown. We therefore compared FXR expression in the cardiovascular system in PAH, RHF and a control. Methods and results: Hemodynamic parameters and morphology were assessed in blank solution-exposed control, monocrotaline (MCT)-exposed PAHmore » (4 weeks) and RHF (7 weeks) Sprague–Dawley rats. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blot (WB), immunohistochemistry (IHC) analysis and immunofluorescence (IF) analysis were performed to assess FXR levels in the lung and heart tissues of MCT-induced PAH and RHF rats. In normal rats, low FXR levels were detected in the heart, and nearly no FXR was expressed in rat lungs. However, FXR expression was significantly elevated in PAH and RHF rat lungs but reduced in PAH and RHF rat right ventricular (RV) tissues. FXR expression was reduced only in RHF rat left ventricular (LV) tissues. Conclusions: The differential expression of FXR in MCT-induced PAH lungs and heart tissues in parallel with PAH pathophysiological processes suggests that FXR contributes to PAH. - Highlights: • FXR was expressed in rat lung and heart tissues. • FXR expression increased sharply in the lung tissues of PAH and RHF rats. • FXR expression was reduced in PAH and RHF rat RV tissue. • FXR expression was unaltered in PAH LV but reduced in RHF rat LV tissue. • FXR expression was prominent in the neovascularization region.« less
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Navarini, Susanne; Bellsham-Revell, Hannah; Chubb, Henry; Gu, Haotian; Sinha, Manish D; Simpson, John M
2017-12-01
Systemic arterial hypertension predisposes children to cardiovascular risk in childhood and adult life. Despite extensive study of left ventricular (LV) hypertrophy, detailed 3-dimensional strain analysis of cardiac function in hypertensive children has not been reported. The aim of this study was to evaluate LV mechanics (strain, twist, and torsion) in young patients with hypertension compared with a healthy control group and assess factors associated with functional measurements. Sixty-three patients (26 hypertension and 37 normotensive) were enrolled (mean age, 14.3 and 11.4 years; 54% men and 41% men, respectively). All children underwent clinical evaluation and echocardiographic examination, including 3-dimensional strain. There was no difference in LV volumes and ejection fraction between the groups. Myocardial deformation was significantly reduced in those with hypertension compared with controls. For hypertensive and normotensive groups, respectively, global longitudinal strain was -15.1±2.3 versus -18.5±1.9 ( P <0.0001), global circumferential strain -15.2±3 versus -19.9±3.1 (<0.0001), global radial strain +44.0±11.3 versus 63.4±10.5 ( P <0.0001), and global 3-dimensional strain -26.1±3.8 versus -31.5±3.8 ( P <0.0001). Basal clockwise rotation, apical counterclockwise rotation, twist, and torsion were not significantly different. After multivariate regression analyses blood pressure, body mass index and LV mass maintained a significant relationship with measures of LV strain. Similar ventricular volumes and ejection fraction were observed in hypertensive and normotensive children, but children with hypertension had significantly lower strain indices. Whether reduced strain might predict future cardiovascular risk merits further longitudinal study. © 2017 American Heart Association, Inc.
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A new ALF from Litopenaeus vannamei and its SNPs related to WSSV resistance
NASA Astrophysics Data System (ADS)
Liu, Jingwen; Yu, Yang; Li, Fuhua; Zhang, Xiaojun; Xiang, Jianhai
2014-11-01
Anti-lipopolysaccharide factors (ALFs) are basic components of the crustacean immune system that defend against a range of pathogens. The cDNA sequence of a new ALF, designated nLvALF2, with an open reading frame encoding 132 amino acids was cloned. Its deduced amino acid sequence contained the conserved functional domain of ALFs, the LPS binding domain (LBD). Its genomic sequence consisted of three exons and four introns. nLvALF2 was mainly expressed in the Oka organ and gills of shrimps. The transcriptional level of nLvALF2 increased significantly after white spot syndrome virus (WSSV) infection, suggesting its important roles in protecting shrimps from WSSV. Single nucleotide polymorphisms (SNPs) were found in the genomic sequence of nLvALF2, of which 38 were analyzed for associations with the susceptibility/resistance of shrimps to WSSV. The loci g.2422 A>G, g.2466 T>C, and g.2529 G>A were significantly associated with the resistance to WSSV ( P<0.05). These SNP loci could be developed as markers for selection of WSSV-resistant varieties of Litopenaeus vannamei.
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Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F.; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping
2015-01-01
Background Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cadiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca2+]i transient ([Ca2+]iT), and β-adrenergic hyporesponsiveness. Methods and Results We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca2+]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400W, 10−5 mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca2+]iT. In hypothyroidism, isoproterenol (10−8 M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca2+]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca2+]iT. Conclusions Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cadiomyocyte iNOS may promote progressive cardiac dysfunction in hypothyroidism. PMID:26681542
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Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping
2016-02-01
Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cardiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca(2+)]i transient ([Ca(2+)]iT), and β-adrenergic hyporesponsiveness. We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca(2+)]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400 W, 10(-5)mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca(2+)]iT. In hypothyroidism, isoproterenol (10(-8)M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca(2+)]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca(2+)]iT. Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cardiomyocyte iNOS may promote progressive cardiac dysfunction in hypothyroidism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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von Knobelsdorff-Brenkenhoff, Florian; Karunaharamoorthy, Achudhan; Trauzeddel, Ralf Felix; Barker, Alex J; Blaszczyk, Edyta; Markl, Michael; Schulz-Menger, Jeanette
2016-03-01
Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. The aim of this study was to describe blood flow patterns in the ascending aorta of patients with AS and determine their association with remodeling. Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age, 63±13 years) and 37 healthy controls (age, 60±10 years) underwent 4-dimensional-flow magnetic resonance imaging. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index and the ratio of LV mass:end-diastolic volume (relative wall mass). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and patients with AS exhibited an asymmetrical and elevated distribution of peak systolic wall shear stress. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (P=0.0274), eccentricity (P=0.0070), and flow displacement (P=0.0021). Bicuspid aortic valve was associated with more intense helical (P=0.0098) and vortical flow formation (P=0.0536), higher flow displacement (P=0.11), and higher peak systolic wall shear stress (P=0.0926). LV mass index and relative wall mass were significantly associated with aortic orifice area (P=0.0611, P=0.0058) and flow displacement (P=0.0058, P=0.0283). In this pilot study, AS leads to abnormal blood flow pattern and peak systolic wall shear stress in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling. © 2016 American Heart Association, Inc.
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Treating a 20 mm Hg gradient alleviates myocardial hypertrophy in experimental aortic coarctation.
Wendell, David C; Friehs, Ingeborg; Samyn, Margaret M; Harmann, Leanne M; LaDisa, John F
2017-10-01
Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 × 14-cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. LV mass was elevated for CoA (5.2 ± 0.55 g) versus control (3.6 ± 0.16 g) and corrected (4.0 ± 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV's perspective. Copyright © 2017 Elsevier Inc. All rights reserved.
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Marques, Pedro; Nobre Menezes, Miguel; Lima da Silva, Gustavo; Bernardes, Ana; Magalhães, Andreia; Cortez-Dias, Nuno; Carpinteiro, Luís; de Sousa, João; Pinto, Fausto J
2016-06-01
Multi-site pacing is emerging as a new method for improving response to cardiac resynchronization therapy (CRT), but has been little studied, especially in patients with atrial fibrillation. We aimed to assess the effects of triple-site (Tri-V) vs. biventricular (Bi-V) pacing on hemodynamics and QRS duration. This was a prospective observational study of patients with permanent atrial fibrillation and ejection fraction <40% undergoing CRT implantation (n=40). One right ventricular (RV) lead was implanted in the apex and another in the right ventricular outflow tract (RVOT) septal wall. A left ventricular (LV) lead was implanted in a conventional venous epicardial position. Cardiac output (using the FloTrac™ Vigileo™ system), mean QRS and ejection fraction were calculated. Mean cardiac output was 4.81±0.97 l/min with Tri-V, 4.68±0.94 l/min with RVOT septal and LV pacing, and 4.68±0.94 l/min with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV). Mean pre-implantation QRS was 170±25 ms, 123±18 ms with Tri-V, 141±25 ms with RVOT septal pacing and LV pacing and 145±19 with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV and pre-implantation). Mean ejection fraction was significantly higher with Tri-V (30±11%) vs. Bi-V pacing (28±12% with RVOT septal and LV pacing and 28±11 with RV apical and LV pacing) and pre-implantation (25±8%). Tri-V pacing produced higher cardiac output and shorter QRS duration than Bi-V pacing. This may have a significant impact on the future of CRT. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.
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NASA Astrophysics Data System (ADS)
Koryanov, Vsevolod; Harri, Ari-Matti; Kazakovtcev, Victor
At present paper analyzes the dynamics of movement of the landing vehicle (LV) with an inflatable braking device (IBD). During the movement in the planet's atmosphere with LV with IBD are significant aerodynamic loads, which can lead to a change in a non-rigid shape and appearance of the shell IBD current asymmetries LV with IBD. The presence arising in the manufacture of structural LV asymmetry results in a stabilized descent in the process of turning the LV with IBD various dynamic phenomena, such as the vibrational-rotational resonance, the resonance autorotation, altering the dynamics of angular motion of the LV. As a result of work carried out, among others, the following conclusions: 1. In the first step of descent of landing vehicle possible high angles of attack, however, the very small quantities of the velocity head. 2. In the second phase of descent arise spatial angles of attack, caused by small structural asymmetries of LV. These angles of attack, together with increasing magnitude of the velocity head cause these significant increase in lateral load. The increase in the transverse load leads to an increase in the asymmetry of the external form, which causes an additional increase in the spatial angle of attack. Depending on the magnitude of the transverse stiffness IBD or leads to a certain additional increase in the spatial angle of attack, or a possible buckling landing vehicle. 3. In the third (final) stage of the descent at subsonic speed landing vehicle with additional inflatable braking device does not influence the stiffness braking, changing the dynamics of angular motion slightly. This is due to the small size of the ram on the subsonic long trajectory and, accordingly, small deformation additional inflatable braking device. This research was supported by the European Commission Seventh Framework Programme FP7/2007-2013 under grant agreement n 263255 RITD.
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Babcock, Matthew C; Lefferts, Wesley K; Heffernan, Kevin S
2017-07-01
Left ventricular (LV) structure and function are predictors of cardiovascular (CV) morbidity and mortality and are related to resting peripheral haemodynamic load in older adults. The central haemodynamic response to exercise may reveal associations with LV structure and function not detected by traditional peripheral (brachial) measures in a younger population. To examine correlations between acute exercise-induced changes in central artery stiffness and wave reflections and measures of resting LV structure and function. Sixteen healthy men (age 26 ± 6 year; BMI 25·3 ± 2·7 kg m -2 ) had measures of central haemodynamic load measured before/after a 30-s Wingate anaerobic test (WAT). Common carotid artery stiffness and reflected wave intensity were assessed via wave intensity analysis as a regional pulse wave velocity (PWV) and negative area (NA), respectively. Resting LV structure (LV mass) and function [midwall fractional shortening (mFS)] were assessed using M-mode echocardiography in the parasternal short-axis view. There was a significant association between mFS and WAT-mediated change in carotid systolic BP (r = -0·57, P = 0·011), logNA (r = -0·58, P = 0·009) and PWV (r = -0·44, P = 0·045). There were no significant associations between resting mFS and changes in brachial systolic BP (r = -0·26, P>0·05). There were no associations between resting LV mass and changes in any haemodynamic variable (P>0·05). Exercise-induced increases in central haemodynamic load reveal associations with lower resting LV function in young healthy men undetected by traditional peripheral haemodynamics. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.
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Prats, A C; Sarih, L; Gabus, C; Litvak, S; Keith, G; Darlix, J L
1988-01-01
Retrovirus virions carry a diploid genome associated with a large number of small viral finger protein molecules which are required for encapsidation. Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome. An RSV mutant with a Val-Pro insertion in the finger motif of p12 is able to partially encapsidate genomic RNA but is not infectious because mutated p12 is incapable of positioning the replication primer, tRNATrp. Since all known replication competent retroviruses, and the plant virus CaMV, code for finger proteins analogous to RSV p12 or MuLV p10, the initial stage of reverse transcription in avian, mammalian and human retroviruses and in CaMV is probably controlled in an analogous way. Images PMID:2458920
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Prats, A C; Sarih, L; Gabus, C; Litvak, S; Keith, G; Darlix, J L
1988-06-01
Retrovirus virions carry a diploid genome associated with a large number of small viral finger protein molecules which are required for encapsidation. Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome. An RSV mutant with a Val-Pro insertion in the finger motif of p12 is able to partially encapsidate genomic RNA but is not infectious because mutated p12 is incapable of positioning the replication primer, tRNATrp. Since all known replication competent retroviruses, and the plant virus CaMV, code for finger proteins analogous to RSV p12 or MuLV p10, the initial stage of reverse transcription in avian, mammalian and human retroviruses and in CaMV is probably controlled in an analogous way.
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Little, Susan; Sears, William; Lachtara, Jessica; Bienzle, Dorothee
2009-06-01
The purposes of this study were to determine the seroprevalence of feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infection among cats in Canada and to identify risk factors for seropositivity. Signalment, lifestyle factors, and test results for FeLV antigen and FIV antibody were analyzed for 11 144 cats from the 10 Canadian provinces. Seroprevalence for FIV antibody was 4.3% and seroprevalence for FeLV antigen was 3.4%. Fifty-eight cats (0.5%) were seropositive for both viruses. Seroprevalence varied geographically. Factors such as age, gender, health status, and lifestyle were significantly associated with risk of FeLV and FIV seropositivity. The results suggest that cats in Canada are at risk of retrovirus infection and support current recommendations that the retrovirus status of all cats should be known.
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Webster, Lynn R.; Smith, Michael D.; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M.
2017-01-01
Abstract Objective. To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. Methods. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (Emax; primary endpoint) using drug liking visual analog scale (VAS) score, Emax using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Results. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking Emax was significantly lower (P < 0.0001) compared with IN morphine ER. Overall drug liking and TDA Emax values were significantly lower (P < 0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). Conclusions. All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. PMID:27651510
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Mattila, Minttu; Koskenvuo, Juha; Söderström, Mirva; Eerola, Kim; Savontaus, Mikko
2016-07-01
Doxorubicin is an effective anticancer drug. The major limitation to its use is the induction of dose-dependent cardiomyopathy. No specific treatment exists for doxorubicin-induced cardiomyopathy and treatments used for other forms of heart failure have only limited beneficial effects. The contraction-relaxation cycle of the heart is controlled by cytosolic calcium concentrations, which, in turn, are critically regulated by the activity of the sarcoplasmic reticulum Ca(2) (+) ATPase (SERCA2a) pump. We hypothesized that SERCA2a gene transfer would ameliorate doxorubicin-induced cardiomyopathy. Lentiviral vectors LV-SERCA2a-GFP and LV-GFP were constructed and in vitro gene transfer of LV-SERCA2a-GFP confirmed SERCA2a expression by western blot analysis. Heart failure was induced by giving a single intraperitoneal injection of doxorubicin. LV-SERCA2a-GFP, LV-GFP vectors and phosphate-buffered saline (PBS) were injected under echocardiographic control to the anterior wall of the left ventricle. Echocardiography analyses were performed on the injection day and 28 days postinjection. On the injection day, there were no significant differences in the average ejection fractions (EFs) among SERCA2a (40.0%), GFP (41.1%) and PBS (39.4%) injected animals. On day 28, EF in the SERCA2a group had increased by 16.6 ± 6.7% to 46.4 ± 2.1%. By contrast, EFs in the GFP (40.2 ± 1.3%) and PBS (40.6 ± 1.4%) groups remained at pre-injection levels. In addition, end systolic and end diastolic left ventricle volumes were significantly smaller in the SERCA2a group compared to controls. SERCA2a gene transfer significantly improves left ventricle function and dimensions in doxorubicin-induced cardiomyopathy, thus making LV-SERCA2a gene transfer an attractive treatment modality for doxorubicin-induced heart failure. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
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Left Ventricular Strain in Chemotherapy-Naive and Radiotherapy-Naive Patients With Cancer.
Tadic, Marijana; Genger, Martin; Baudisch, Ana; Kelle, Sebastian; Cuspidi, Cesare; Belyavskiy, Evgeny; Burkhardt, Franziska; Venneri, Lucia; Attanasio, Philipp; Pieske, Burkert
2018-03-01
We sought to investigate left ventricular (LV) function and mechanics in patients with cancer before they received chemotherapy or radiotherapy, as well as the relationship between cancer and reduced LV multidirectional strain in the whole study population. The retrospective study involved 122 chemotherapy- and radiotherapy-naive patients with cancer and 45 age- and sex-matched controls with a cardiovascular risk profile similar to that of the patients with cancer. All the patients underwent echocardiographic examination before introduction of chemotherapy or radiotherapy. LV longitudinal (-19.1% ± 2.1% vs -17.8% ± 3.5%; P = 0.022), circumferential (-22.9% ± 3.5% vs -20.1% ± 4.1%; P < 0.001), and radial (40.5% ± 8.8% vs 35.2% ± 10.7%; P = 0.004) strain was significantly lower in the patients with cancer than in the control group. Endocardial and midmyocardial longitudinal LV strain was significantly reduced in the patients with cancer compared with the controls, whereas epicardial longitudinal strain was similar between these groups. Endocardial, midmyocardial, and epicardial circumferential strain was significantly lower in the chemotherapy- or radiotherapy-naive patients with cancer than in the controls. Cancer was associated with reduced longitudinal (odds ratio [OR], 9.0; 95% confidence interval [CI], 2.20-23.50; P < 0.001), reduced circumferential (OR, 7.1; 95% CI, 3.80-20.40; P < 0.001), and reduced radial strain (OR, 7.2; 95% CI, 3.41-25.10; P < 0.001) independent of age, sex, body mass index, diabetes, and hypertension. LV mechanics was impaired in the patients with cancer compared with the controls even before initiation of chemotherapy and radiotherapy. Cancer and hypertension were associated with reduced LV multidirectional strain independent of other clinical parameters. The present results indicate that cancer itself potentially induces cardiac remodelling independent of chemotherapy and radiotherapy. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Olivotto, Iacopo; Maron, Barry J; Appelbaum, Evan; Harrigan, Caitlin J; Salton, Carol; Gibson, C Michael; Udelson, James E; O'Donnell, Christopher; Lesser, John R; Manning, Warren J; Maron, Martin S
2010-07-15
In hypertrophic cardiomyopathy (HCM), the clinical significance attributable to the broad range of left ventricular (LV) systolic function, assessed as the ejection fraction (EF), is incompletely resolved. We evaluated the EF using cardiovascular magnetic resonance (CMR) imaging in a large cohort of patients with HCM with respect to the clinical status and evidence of left ventricular remodeling with late gadolinium enhancement (LGE). CMR imaging was performed in 310 consecutive patients, aged 42 +/- 17 years. The EF in patients with HCM was 71 +/- 10% (range 28% to 89%), exceeding that of 606 healthy controls without cardiovascular disease (66 +/- 5%, p <0.001). LGE reflecting LV remodeling showed an independent, inverse relation to the EF (B-0.69, 95% confidence interval -0.86 to -0.52; p <0.001) and was greatest in patients with an EF <50%, in whom it constituted a median value of 29% of the LV volume (interquartile range 16% to 40%). However, the substantial subgroup with low-normal EF values of 50% to 65% (n = 45; 15% of the whole cohort), who were mostly asymptomatic or mildly symptomatic (37 or 82% with New York Heart Association functional class I to II), showed substantial LGE (median 5% of LV volume, interquartile range 2% to 10%). This overlapped with the subgroup with systolic dysfunction and significantly exceeded that of patients with an EF of 66% to 75% and >75% (median 2% of the LV volume, interquartile range 1.5% to 4%; p <0.01). In conclusion, in a large cohort of patients with HCM, a subset of patients with low-normal EF values (50% to 65%) was identified by contrast-enhanced CMR imaging as having substantial degrees of LGE, suggesting a transition phase, potentially heralding advanced LV remodeling and systolic dysfunction, with implications for clinical surveillance and management. Copyright (c) 2010. Published by Elsevier Inc.
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Vasan, Ramachandran S; Glazer, Nicole L; Felix, Janine F; Lieb, Wolfgang; Wild, Philipp S; Felix, Stephan B; Watzinger, Norbert; Larson, Martin G; Smith, Nicholas L; Dehghan, Abbas; Grosshennig, Anika; Schillert, Arne; Teumer, Alexander; Schmidt, Reinhold; Kathiresan, Sekar; Lumley, Thomas; Aulchenko, Yurii S; König, Inke R; Zeller, Tanja; Homuth, Georg; Struchalin, Maksim; Aragam, Jayashri; Bis, Joshua C; Rivadeneira, Fernando; Erdmann, Jeanette; Schnabel, Renate B; Dörr, Marcus; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J; Greiser, Karin Halina; Levy, Daniel; Haritunians, Talin; Deckers, Jaap W; Stritzke, Jan; Lackner, Karl J; Völker, Uwe; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; O'Donnell, Christopher J; Heckbert, Susan R; Stricker, Bruno H; Ziegler, Andreas; Reffelmann, Thorsten; Redfield, Margaret M; Werdan, Karl; Mitchell, Gary F; Rice, Kenneth; Arnett, Donna K; Hofman, Albert; Gottdiener, John S; Uitterlinden, Andre G; Meitinger, Thomas; Blettner, Maria; Friedrich, Nele; Wang, Thomas J; Psaty, Bruce M; van Duijn, Cornelia M; Wichmann, H-Erich; Munzel, Thomas F; Kroemer, Heyo K; Benjamin, Emelia J; Rotter, Jerome I; Witteman, Jacqueline C; Schunkert, Heribert; Schmidt, Helena; Völzke, Henry; Blankenberg, Stefan
2009-07-08
Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
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Huang, Ching-Hui; Chang, Chia-Chu; Kuo, Chen-Ling; Huang, Ching-Shan; Lin, Chih-Sheng; Liu, Chin-San
2015-01-01
Background: Cyclophilin A (CyPA) concentration increases in acute coronary syndrome. In an animal model of acute myocardial infarction, administration of angiotensin-converting-enzyme inhibitor was associated with lower left ventricular (LV) CyPA concentration and improved LV performance. This study investigated the relationships between changes in plasma CyPA concentrations and LV remodeling in patients with ST-elevation myocardial infarction (STEMI). Methods and Results: We enrolled 55 patients who underwent percutaneous coronary intervention for acute STEMI. Plasma CyPA, matrix metalloproteinase (MMP), interleukin-6 and high-sensitivity C-reactive protein concentrations were measured at baseline and at one-month follow-up. Echocardiography was performed at baseline and at one-, three-, and six-month follow-up. Patients with a decrease in baseline CyPA concentration at one-month follow-up (n = 28) had a significant increase in LV ejection fraction (LVEF) (from 60.2 ± 11.5% to 64.6 ± 9.9%, p < 0. 001) and preserved LV synchrony at six months. Patients without a decrease in CyPA concentration at one month (n = 27) did not show improvement in LVEF and had a significantly increased systolic dyssynchrony index (SDI) (from 1.170 ± 0.510% to 1.637 ± 1.299%, p = 0.042) at six months. Multiple linear regression analysis showed a significant association between one-month CyPA concentration and six-month LVEF. The one-month MMP-2 concentration was positively correlated with one-month CyPA concentration and LV SDI. Conclusions: Decreased CyPA concentration at one-month follow-up after STEMI was associated with better LVEF and SDI at six months. Changes in CyPA, therefore, may be a prognosticator of patient outcome. PMID:25552928
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Gray, Michelle; Powers, Melissa; Boyd, Larissa; Garver, Kayla
2018-03-22
Functional mobility disability affects more than one in five adults over 70 years and increases to 80% by 90 years. While negative changes in mobility are multifactorial, deleterious body composition changes contribute significantly. Resistance training alters the negative trajectory of physical function as well as increases lean mass among older adults. Recently, high-velocity (HV) resistance training has been indicated as an effective intervention to increase lean mass and functional performance. The present investigation compared body composition, physical function, and muscular strength changes between HV and LV resistance training programs. Participants > 65 years (n = 53) were randomly assigned to LV, HV, or active control (AC) group and participated in their respective intervention for 48 weeks. Analysis of covariance revealed no significant body composition changes over time between groups (p > 0.05). Eight-foot up-and-go performance improved in the HV and AC groups (p < 0.05) with no change in the LV group (p > 0.05) over time. Muscular strength increased in both the LV and HV groups within the first 24 weeks, while only in the LV group, muscular strength continued to increase from 24 to 48 weeks (p < 0.05). Resistance training appears to be an effective intervention for improving aspects of physical function and muscular strength; however, no significant changes in body composition were observed over the 48-week intervention. Findings from the current investigation support use of resistance training for improving physical function among community-dwelling older adults.
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Zuozienė, Gitana; Laucevičius, Aleksandras; Leibowitz, David
2012-01-01
Medical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. Patients with Canadian Cardiovascular Society (CCS) class III-IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. Twenty patients (four women, 16 men; mean age 64 years, range 45-83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). This study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.
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Iwano, Hiroyuki; Kamimura, Daisuke; Fox, Ervin R; Hall, Michael E; Vlachos, Pavlos; Little, William C
2016-12-01
Early-diastolic left ventricular (LV) longitudinal expansion is delayed with diastolic dysfunction. We hypothesized that, in patients with heart failure (HF), regardless of LV ejection fraction (EF), there is diastolic temporal nonuniformity with a delay of longitudinal relative to circumferential expansion. Echocardiography was performed in 143 HF patients-50 with preserved EF (HFpEF) and 93 with reduced EF (HFrEF)-as well as 31 normal control subjects. The delay of early-diastolic mitral annular velocity from the mitral Doppler E (T E-e' ) was measured as a parameter of the longitudinal expansion delay. The delay of the longitudinal early-diastolic global strain rate (SR E ) relative to circumferential SR E (Delay C-L ) was calculated as a parameter of temporal nonuniformity. Intra-LV pressure difference (IVPD) was estimated with the use of color M-mode Doppler data as a parameter of LV diastolic suction. Although normal control subjects had symmetric LV expansion in early diastole, T E-e' and Delay C-L were significantly prolonged in HF regardless of EF (P < .01 vs control for all). Multivariate analysis revealed that Delay C-L was the independent determinant of IVPD among the parameters of LV geometry and contraction (β = -0.21; P < .05). An abnormal temporal nonuniformity of early-diastolic expansion is present in HF regardless of EF, which was associated with reduced LV suction. Copyright © 2016 Elsevier Inc. All rights reserved.
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Arterial wave reflection and subclinical left ventricular systolic dysfunction.
Russo, Cesare; Jin, Zhezhen; Takei, Yasuyoshi; Hasegawa, Takuya; Koshaka, Shun; Palmieri, Vittorio; Elkind, Mitchell Sv; Homma, Shunichi; Sacco, Ralph L; Di Tullio, Marco R
2011-03-01
Increased arterial wave reflection is a predictor of cardiovascular events and has been hypothesized to be a cofactor in the pathophysiology of heart failure. Whether increased wave reflection is inversely associated with left-ventricular (LV) systolic function in individuals without heart failure is not clear. Arterial wave reflection and LV systolic function were assessed in 301 participants from the Cardiovascular Abnormalities and Brain Lesions (CABL) study using two-dimensional echocardiography and applanation tonometry of the radial artery to derive central arterial waveform by a validated transfer function. Aortic augmentation index (AIx) and wasted energy index (WEi) were used as indices of wave reflection. LV systolic function was measured by LV ejection fraction (LVEF) and tissue Doppler imaging (TDI). Mitral annulus peak systolic velocity (Sm), peak longitudinal strain and strain rate were measured. Participants with history of coronary artery disease, atrial fibrillation, LVEF less than 50% or wall motion abnormalities were excluded. Mean age of the study population was 68.3 ± 10.2 years (64.1% women, 65% hypertensive). LV systolic function by TDI was lower with increasing wave reflection, whereas LVEF was not. In multivariate analysis, TDI parameters of LV longitudinal systolic function were significantly and inversely correlated to AIx and WEi (P values from 0.05 to 0.002). In a community cohort without heart failure and with normal LVEF, an increased arterial wave reflection was associated with subclinical reduction in LV systolic function assessed by novel TDI techniques. Further studies are needed to investigate the prognostic implications of this relationship.
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Acute and chronic neuromuscular adaptations to local vibration training.
Souron, Robin; Besson, Thibault; Millet, Guillaume Y; Lapole, Thomas
2017-10-01
Vibratory stimuli are thought to have the potential to promote neural and/or muscular (re)conditioning. This has been well described for whole-body vibration (WBV), which is commonly used as a training method to improve strength and/or functional abilities. Yet, this technique may present some limitations, especially in clinical settings where patients are unable to maintain an active position during the vibration exposure. Thus, a local vibration (LV) technique, which consists of applying portable vibrators directly over the tendon or muscle belly without active contribution from the participant, may present an alternative to WBV. The purpose of this narrative review is (1) to provide a comprehensive overview of the literature related to the acute and chronic neuromuscular changes associated with LV, and (2) to show that LV training may be an innovative and efficient alternative method to the 'classic' training programs, including in the context of muscle deconditioning prevention or rehabilitation. An acute LV application (one bout of 20-60 min) may be considered as a significant neuromuscular workload, as demonstrated by an impairment of force generating capacity and LV-induced neural changes. Accordingly, it has been reported that a training period of LV is efficient in improving muscular performance over a wide range of training (duration, number of session) and vibration (frequency, amplitude, site of application) parameters. The functional improvements are principally triggered by adaptations within the central nervous system. A model illustrating the current research on LV-induced adaptations is provided.
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Peterson, Gail E; de Backer, Tine; Contreras, Gabriel; Wang, Xuelei; Kendrick, Cynthia; Greene, Tom; Appel, Lawrence J; Randall, Otelio S; Lea, Janice; Smogorzewski, Miroslaw; Vagaonescu, Tudor; Phillips, Robert A
2013-09-01
African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05-1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (P<0.05) associated with future heart failure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.
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Whole Body Vibration Reduces Inflammatory Bone Loss in a Lipopolysaccharide Murine Model.
Kim, I S; Lee, B; Yoo, S J; Hwang, S J
2014-07-01
Whole body vibration (WBV) stimulation has a beneficial effect on the recovery of osteoporotic bone. We aimed to investigate the immediate effect of WBV on lipopolysaccharide (LPS)-mediated inflammatory bone loss by varying the exposure timing. Balb/C mice were divided into the following groups: control, LPS (L), and LPS with vibration (LV). The L and LV groups received LPS (5 mg/kg) by 2 intraperitoneal injections on days 0 and 4. The LV group was exposed to WBV (0.4 g, 45 Hz) either during LPS treatment (LV1) or after cessation of LPS injection (LV2) and then continued WBV treatment for 10 min/d for 3 d. Evaluation based on micro-computed tomography was performed 7 d after the first injection, when the L group showed a significant decrease in bone volume (-25.8%) and bone mineral density (-33.5%) compared with the control group. The LV2 group recovered bone volume (35%) and bone mineral density (19.9%) compared with the L group, whereas the LV1 group showed no improvement. This vibratory signal showed a suppressive effect on the LPS-mediated induction of inflammatory cytokines such as IL-1β or TNF-α in human mesenchymal stem cells in vitro. These findings suggest that immediate exposure to WBV after the conclusion of LPS treatment efficiently reduces trabecular bone loss, but WBV might be less effective during the course of treatment with inflammatory factor. © International & American Associations for Dental Research.
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Whole Body Vibration Reduces Inflammatory Bone Loss in a Lipopolysaccharide Murine Model
Kim, I.S.; Lee, B.; Yoo, S.J.; Hwang, S.J.
2014-01-01
Whole body vibration (WBV) stimulation has a beneficial effect on the recovery of osteoporotic bone. We aimed to investigate the immediate effect of WBV on lipopolysaccharide (LPS)–mediated inflammatory bone loss by varying the exposure timing. Balb/C mice were divided into the following groups: control, LPS (L), and LPS with vibration (LV). The L and LV groups received LPS (5 mg/kg) by 2 intraperitoneal injections on days 0 and 4. The LV group was exposed to WBV (0.4 g, 45 Hz) either during LPS treatment (LV1) or after cessation of LPS injection (LV2) and then continued WBV treatment for 10 min/d for 3 d. Evaluation based on micro–computed tomography was performed 7 d after the first injection, when the L group showed a significant decrease in bone volume (−25.8%) and bone mineral density (−33.5%) compared with the control group. The LV2 group recovered bone volume (35%) and bone mineral density (19.9%) compared with the L group, whereas the LV1 group showed no improvement. This vibratory signal showed a suppressive effect on the LPS-mediated induction of inflammatory cytokines such as IL-1β or TNF-α in human mesenchymal stem cells in vitro. These findings suggest that immediate exposure to WBV after the conclusion of LPS treatment efficiently reduces trabecular bone loss, but WBV might be less effective during the course of treatment with inflammatory factor. PMID:24810275
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Granér, Marit; Nyman, Kristofer; Siren, Reijo; Pentikäinen, Markku O; Lundbom, Jesper; Hakkarainen, Antti; Lauerma, Kirsi; Lundbom, Nina; Nieminen, Markku S; Taskinen, Marja-Riitta
2015-01-01
Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study. © 2014 American Heart Association, Inc.
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Hong, Tae Hee; Byun, Joung Hun; Lee, Hee Moon; Kim, Yong Hwan; Kang, Gu-Hyun; Oh, Ju Hyeon; Hwang, Sang Won; Kim, Han Yong; Park, Jae Hong; Jung, Jae Jun
2016-01-01
Extracorporeal membrane oxygenation (ECMO) has become one of the often applied mechanical support for acute cardiogenic shock. During venoarterial (VA) ECMO support, left heart decompression should be considered when left ventricular (LV) distension develops with pulmonary edema and LV dysfunction. The aim of this study was to report the results of transaortic catheter venting (TACV), as an alternative venting method, performed during VA-ECMO in patients with acute cardiogenic shock. We retrospectively reviewed the records of seven patients who underwent both ECMO and TACV between February 2013 and February 2014. Extracorporeal membrane oxygenation was performed uneventfully, and TACV was introduced under transthoracic echocardiographic guidance in all cases. Hemodynamic parameters, LV ejection fraction, and LV end-diastolic dimension (LVEDD) were measured 24 hours after initiating TACV in survivors. There were no procedure-related complications. Four of the seven patients (58%) survived. Transaortic catheter venting led to an increase in mean blood pressure in all patients (p = 0.050). There was a significant difference between pre- and post-TACV-LVEDD (59 ± 14 vs. 50 ± 12 mm, p = 0.044), with a 10-23% reduction in LVEDD in survivors. Transaortic catheter venting might be an acceptable alternative to venting procedures and useful for LV recovery during VA-ECMO in patients with severe LV dysfunction.
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CD133-targeted gene transfer into long-term repopulating hematopoietic stem cells.
Brendel, Christian; Goebel, Benjamin; Daniela, Abriss; Brugman, Martijn; Kneissl, Sabrina; Schwäble, Joachim; Kaufmann, Kerstin B; Müller-Kuller, Uta; Kunkel, Hana; Chen-Wichmann, Linping; Abel, Tobias; Serve, Hubert; Bystrykh, Leonid; Buchholz, Christian J; Grez, Manuel
2015-01-01
Gene therapy for hematological disorders relies on the genetic modification of CD34(+) cells, a heterogeneous cell population containing about 0.01% long-term repopulating cells. Here, we show that the lentiviral vector CD133-LV, which uses a surface marker on human primitive hematopoietic stem cells (HSCs) as entry receptor, transfers genes preferentially into cells with high engraftment capability. Transduction of unstimulated CD34(+) cells with CD133-LV resulted in gene marking of cells with competitive proliferative advantage in vitro and in immunodeficient mice. The CD133-LV-transduced population contained significantly more cells with repopulating capacity than cells transduced with vesicular stomatitis virus (VSV)-LV, a lentiviral vector pseudotyped with the vesicular stomatitis virus G protein. Upon transfer of a barcode library, CD133-LV-transduced cells sustained gene marking in vivo for a prolonged period of time with a 6.7-fold higher recovery of barcodes compared to transduced control cells. Moreover, CD133-LV-transduced cells were capable of repopulating secondary recipients. Lastly, we show that this targeting strategy can be used for transfer of a therapeutic gene into CD34(+) cells obtained from patients suffering of X-linked chronic granulomatous disease. In conclusion, direct gene transfer into CD133(+) cells allows for sustained long-term engraftment of gene corrected cells.
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Laoong-u-thai, Yanisa; Zhao, Baoping; Phongdara, Amornrat; Ako, Harry; Yang, Jinzeng
2009-01-01
Small ubiquitin-like modifiers (SUMO) work in a similar way as ubiquitin to alter the biological properties of a target protein by conjugation. A shrimp SUMO cDNA named LvSUMO-1 was identified in Litopenaeus vannamei. LvSUMO-1 cDNA contains a coding sequence of 282 nucleotides with untranslated regions of 37 bp at 5'-end and 347 bp at 3'-end, respectively. The deduced 93 amino acids exhibit 83% identity with the Western Honeybee SUMO-1, and more than 65% homologies with human and mouse SUMO-1. LvSUMO-1 mRNA is expressed in most L. vannamei tissues with the highest level in hepatopancrease. The mRNA expression of LvSUMO-1 over development stages in L. Vammamei is distinguished by a low level in nauplius stage and relatively high level in postlarva stage with continuous expression until juvenile stage. The LvSUMO-1 protein and its conjugated proteins are detected in both cytoplasm and nucleus in several tissues. Interestingly, LvSUMO-1 mRNA levels are high in abdominal muscle during the premolt stage, wherein it has significant activities of protein degradation, suggesting its possible role in the regulation of shrimp muscle protein degradation. PMID:19240809
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Kutner, Robert H; Puthli, Sharon; Marino, Michael P; Reiser, Jakob
2009-01-01
Background During the past twelve years, lentiviral (LV) vectors have emerged as valuable tools for transgene delivery because of their ability to transduce nondividing cells and their capacity to sustain long-term transgene expression in target cells in vitro and in vivo. However, despite significant progress, the production and concentration of high-titer, high-quality LV vector stocks is still cumbersome and costly. Methods Here we present a simplified protocol for LV vector production on a laboratory scale using HYPERFlask vessels. HYPERFlask vessels are high-yield, high-performance flasks that utilize a multilayered gas permeable growth surface for efficient gas exchange, allowing convenient production of high-titer LV vectors. For subsequent concentration of LV vector stocks produced in this way, we describe a facile protocol involving Mustang Q anion exchange membrane chromatography. Results Our results show that unconcentrated LV vector stocks with titers in excess of 108 transduction units (TU) per ml were obtained using HYPERFlasks and that these titers were higher than those produced in parallel using regular 150-cm2 tissue culture dishes. We also show that up to 500 ml of an unconcentrated LV vector stock prepared using a HYPERFlask vessel could be concentrated using a single Mustang Q Acrodisc with a membrane volume of 0.18 ml. Up to 5.3 × 1010 TU were recovered from a single HYPERFlask vessel. Conclusion The protocol described here is easy to implement and should facilitate high-titer LV vector production for preclinical studies in animal models without the need for multiple tissue culture dishes and ultracentrifugation-based concentration protocols. PMID:19220915
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Wang, Sheng; Li, Mengqiao; Yin, Bin; Li, Haoyang; Xiao, Bang; Lǚ, Kai; Huang, Zhijian; Li, Sedong; He, Jianguo; Li, Chaozheng
2017-08-01
Mammalian TAB1 has been previously identified as transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) binding protein, which functions as the activator of TAK1 and p38. This report, for the first time, identified and characterized the homolog of TAB1 in shrimp, to be specific, the homolog gene from Litopenaeus vannamei, containing a 1560-bp open reading frame (ORF) that encoded a putative protein of 519 amino acids with the conserved PP2Cc (Serine/threonine phosphatases, family 2C, catalytic) domain in N-terminal and a TAK1 binding motif in C-terminus, has been cloned and named LvTAB1. LvTAB1 was most abundant in gills and its expression could respond significantly to a series of stimuli, including LPS, Vibrio parahemolyticus and Staphylococcus aureus. Moreover, Co-immunoprecipitation (Co-IP) experiments showed that LvTAB1 could combine with LvTAK1 as well as Lvp38, two members of IMD-NF-κB/MAPK pathway, which meant LvTAB1 could have a role in regulating the activities of these kinases. Over-expression of LvTAB1 in drosophila S2 cells could improve the transcriptional levels of antimicrobial peptide genes (AMPs) such as Diptericin (Dpt), the hallmark of drosophila NF-κB activated genes, indicating its activation effect on NF-κB pathway. Furthermore, suppression of LvTAB1 expression in vivo by RNA-interference increased the sensibility of shrimps to V. parahaemolyticus infection, implying its protective role against bacterial infection. In conclusion, these results provide some insight into the function of LvTAB1 during bacterial infection. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Feline leukaemia. ABCD guidelines on prevention and management.
Lutz, Hans; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; Hosie, Margaret J; Lloret, Albert; Marsilio, Fulvio; Pennisi, Maria Grazia; Radford, Alan D; Thiry, Etienne; Truyen, Uwe; Horzinek, Marian C
2009-07-01
Feline leukaemia virus (FeLV) is a retrovirus that may induce depression of the immune system, anaemia and/or lymphoma. Over the past 25 years, the prevalence of FeLV infection has decreased considerably, thanks both to reliable tests for the identification of viraemic carriers and to effective vaccines. Transmission between cats occurs mainly through friendly contacts, but also through biting. In large groups of non-vaccinated cats, around 30-40% will develop persistent viraemia, 30-40% show transient viraemia and 20-30% seroconvert. Young kittens are especially susceptible to FeLV infection. The most common signs of persistent FeLV viraemia are immune suppression, anaemia and lymphoma. Less common signs are immune-mediated disease, chronic enteritis, reproductive disorders and peripheral neuropathies. Most persistently viraemic cats die within 2-3 years. In low-prevalence areas there may be a risk of false-positive results; a doubtful positive test result in a healthy cat should therefore be confirmed, preferably by PCR for provirus. Asymptomatic FeLV-positive cats should be retested. Supportive therapy and good nursing care are required. Secondary infections should be treated promptly. Cats infected with FeLV should remain indoors. Vaccination against common pathogens should be maintained. Inactivated vaccines are recommended. The virus does not survive for long outside the host. All cats with an uncertain FeLV status should be tested prior to vaccination. All healthy cats at potential risk of exposure should be vaccinated against FeLV. Kittens should be vaccinated at 8-9 weeks of age, with a second vaccination at 12 weeks, followed by a booster 1 year later. The ABCD suggests that, in cats older than 3-4 years of age, a booster every 2-3 years suffices, in view of the significantly lower susceptibility of older cats.
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Garg, Sonia; de Lemos, James A; Matulevicius, Susan A; Ayers, Colby; Pandey, Ambarish; Neeland, Ian J; Berry, Jarett D; McColl, Roderick; Maroules, Christopher; Peshock, Ronald M; Drazner, Mark H
2017-08-01
In the conventional paradigm of the progression of left ventricular hypertrophy, a thick-walled left ventricle (LV) ultimately transitions to a dilated cardiomyopathy. There are scant data in humans demonstrating whether this transition occurs commonly without an interval myocardial infarction. Participants (n=1282) from the Dallas Heart Study underwent serial cardiac magnetic resonance ≈7 years apart. Those with interval cardiovascular events and a dilated LV (increased LV end-diastolic volume [EDV] indexed to body surface area) at baseline were excluded. Multivariable linear regression models tested the association of concentric hypertrophy (increased LV mass and LV mass/volume 0.67 ) with change in LVEDV. The study cohort had a median age of 44 years, 57% women, 43% black, and 11% (n=142) baseline concentric hypertrophy. The change in LVEDV in those with versus without concentric hypertrophy was 1 mL (-9 to 12) versus -2 mL (-11 to 7), respectively, P <0.01. In multivariable linear regression models, concentric hypertrophy was associated with larger follow-up LVEDV ( P ≤0.01). The progression to a dilated LV was uncommon (2%, n=25). In the absence of interval myocardial infarction, concentric hypertrophy was associated with a small, but significantly greater, increase in LVEDV after 7-year follow-up. However, the degree of LV enlargement was minimal, and few participants developed a dilated LV. These data suggest that if concentric hypertrophy does progress to a dilated cardiomyopathy, such a transition would occur over a much longer timeframe (eg, decades) and perhaps less common than previously thought. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00344903. © 2017 American Heart Association, Inc.
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Tsao, Connie W; Gona, Philimon N; Salton, Carol J; Chuang, Michael L; Levy, Daniel; Manning, Warren J; O’Donnell, Christopher J
2015-01-01
Background Elevated left ventricular mass index (LVMI) and concentric left ventricular (LV) remodeling are related to adverse cardiovascular disease (CVD) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized. Methods and Results Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65±9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002–2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person-years of follow-up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable-adjusted proportional hazards regression models, each 10-g/m2 increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD, respectively (P=0.004 and P=0.009, respectively). The association between LV mass/LV end-diastolic volume and incident CVD was borderline significant (P=0.053). Multivariable-adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C-statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness). Conclusions Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation. PMID:26374295
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Schouver, Elie-Dan; Moceri, Pamela; Doyen, Denis; Tieulie, Nathalie; Queyrel, Viviane; Baudouy, Delphine; Cerboni, Pierre; Gibelin, Pierre; Leroy, Sylvie; Fuzibet, Jean-Gabriel; Ferrari, Emile
2017-01-15
Cardiac sarcoidosis (CS) is associated with high morbidity and sudden death. The absence of specific symptoms and lack of diagnostic gold standard technique is challenging. New imaging methods could improve the diagnosis of CS. The aim of our study was to assess the role of left ventricular (LV) longitudinal and circumferential strain as estimated by 2D speckle-tracking imaging in patients with diagnosed sarcoidosis without cardiac involvement according to the current guidelines. We investigated the prevalence of LV strain impairment in this population and assessed its relationship with clinical outcomes, composite of mortality, heart failure, arrhythmia and/or secondarily development of CS and cardiac device implantation. We performed a prospective case-control longitudinal study including 35 patients with diagnosed sarcoidosis and normal cardiac function as assessed by standard transthoracic echocardiography and 35 healthy age- and gender-matched controls. All patients underwent a comprehensive echocardiographic study. Mean age of patients was 47.9±14.8years old (22 women). Compared with controls, global LV longitudinal strain (LV GLS) was reduced in sarcoidosis patients: (-17.2±3.1 vs -21.3±1.5%, p<0.0001). Circumferential LV strain was preserved in patients compared to controls (-19.9±-4.3% vs -21.3±1.5%, p=0.12). Impaired LV GLS was significantly associated with clinical outcomes (HR 1.56; [1.16-2.11], p<0.01) on univariate analysis. Speckle-tracking echocardiography revealed decreased longitudinal LV strain in sarcoidosis patients that was associated with outcomes. LV GLS may represent an early marker of myocardial involvement in sarcoidosis patients that needs to be studied further. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Kiran, Viralam S; Tiwari, Ashish
2018-04-06
The aims of this study were to determine the incidence and correlates of left ventricular (LV) dysfunction amongst percutaneous patent ductus arteriosus (PDA) device closure patients, and to propose an indexed parameter for predicting LV dysfunction. In a retrospective cross-sectional analysis of 30 months duration, 447 patients who underwent PDA device closure were studied. The diameter of the PDA at the pulmonary artery end was measured in the angiograms in all patients and was indexed for their body surface area. The indexed PDA size was categorised into group A (1-2.9 mm/m², 35/447), B (3-5.9 mm/m², 254/447), C (6-8.9 mm/m², 66/447) and D (>9 mm/m², 35/447). Systolic LV function was evaluated using echocardiography at frequent intervals. Overall, 62.63% of the patients were female (280/447). At baseline, all 447 patients had normal LV function. LV dysfunction was seen in 102/447 (22.8%) patients with 2.8% in category A (1/35), 10.6% in category B (27/254), 34.1% in category C (42/123) and 91.4% in category D (32/35) after PDA device closure. Correlation of indexed PDA size and LV dysfunction was statistically significant (p<0.05). Accurate prediction of LV dysfunction is important in risk stratification, ICU management and counselling in PDA device closures. Indexed PDA size correlates well with post-procedural LV dysfunction. The authors propose a new classification of PDA utilising this accurate, reproducible and easy to perform parameter, which does not involve any extra cost, for risk stratification and early management in device closure of PDA.
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Filice, Federica; Celio, Marco R; Babalian, Alexandre; Blum, Walter; Szabolcsi, Viktoria
2017-10-15
Aging-associated ependymal-cell pathologies can manifest as ventricular gliosis, ventricle enlargement, or ventricle stenosis. Ventricle stenosis and fusion of the lateral ventricle (LV) walls is associated with a massive decline of the proliferative capacities of the stem cell niche in the affected subventricular zone (SVZ) in aging mice. We examined the brains of adult C57BL/6 mice and found that ependymal cells located in the adhesions of the medial and lateral walls of the rostral LVs upregulated parvalbumin (PV) and displayed reactive phenotype, similarly to injury-reactive ependymal cells. However, PV+ ependymal cells in the LV-wall adhesions, unlike injury-reactive ones, did not express glial fibrillary acidic protein. S100B+/PV+ ependymal cells found in younger mice diminished in the LV-wall adhesions throughout aging. We found that periventricular PV-immunofluorescence showed positive correlation to the grade of LV stenosis in nonaged mice (<10-month-old), and that the extent of LV-wall adhesions and LV stenosis was significantly lower in mid-aged (>10-month-old) PV-knock out (PV-KO) mice. This suggests an involvement of PV+ ependymal cells in aging-associated ventricle stenosis. Additionally, we observed a time-shift in microglial activation in the LV-wall adhesions between age-grouped PV-KO and wild-type mice, suggesting a delay in microglial activation when PV is absent from ependymal cells. Our findings implicate that compromised ependymal cells of the adhering ependymal layers upregulate PV and display phenotype shift to "reactive" ependymal cells in aging-related ventricle stenosis; moreover, they also contribute to the progression of LV-wall fusion associated with a decline of the affected SVZ-stem cell niche in aged mice. © 2017 Wiley Periodicals, Inc.
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Nanasato, M; Ando, A; Isobe, S; Nonokawa, M; Hirayama, H; Tsuboi, N; Ito, T; Hirai, M; Yokota, M; Saito, H
2001-12-01
Electrocardiographically (ECG) gated myocardial SPECT with (99m)Tc-tetrofosmin has been used widely to assess left ventricular (LV) function. However, the accuracy of variables using ECG gated myocardial SPECT with beta-methyl-p-(123)I-iodophenylpentadecanoic acid (BMIPP) has not been well defined. Thirty-six patients (29 men, 7 women; mean age, 61.6 +/- 15.6 y) with ischemic heart disease underwent ECG gated myocardial SPECT with (123)I-BMIPP and with (99m)Tc-tetrofosmin and left ventriculography (LVG) within 1 wk. LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) were determined on gated SPECT using commercially available software for automatic data analysis. These volume-related items on LVG were calculated with an area-length method and were estimated by 2 independent observers to evaluate interobserver validity. The regional wall motion with these methods was assessed visually. LVEF was 41.1% +/- 12.5% on gated SPECT with (123)I-BMIPP, 44.5% +/- 13.1% on gated SPECT with (99m)Tc-tetrofosmin, and 46.0% +/- 12.7% on LVG. Global LV function and regional wall motion between both gated SPECT procedures had excellent correlation (LVEF, r = 0.943; LVEDV, r = 0.934; LVESV, r = 0.952; regional wall motion, kappa = 0.92). However, the correlations of global LV function and regional wall motion between each gated SPECT and LVG were significantly lower. Gated SPECT with (123)I-BMIPP showed the same interobserver validity as gated SPECT with (99m)Tc-tetrofosmin. Gated SPECT with (123)I-BMIPP provides high accuracy with regard to LV function and is sufficiently applicable for use in clinical SPECT. This technique can simultaneously reveal myocardial fatty acid metabolism and LV function, which may be useful to evaluate various cardiac diseases.
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Pan, Chuang; Ishizaki, Shoichiro; Nagashima, Yuji; Gao, Jialong; Watabe, Shugo
2018-02-15
Pigment-binding proteins play important roles in crustacean shell colour change. In this study, a red colour-related pigment-binding protein, designated LvPBP75, was purified from the shell of Litopenaeus vannamei. HPLC and PAGE analysis showed that LvPBP75 was a homogeneous monomer with molecular mass of 75kDa. Peptide mass fingerprint analysis revealed that LvPBP75 belonged to hemocyanin, and the released pigment from heated LvPBP75 showed a λ max at 481nm in acetone. The significant red-colour change temperatures were detected at 30 and 80°C, respectively. Based on the determined amino acid fragments, a full-length cDNA of LvPBP75 was cloned and sequenced. The ORF encodes a protein of 662 amino acids having 80% identity with penaeidae hemocyanin. These results strongly suggest a novel function of hemocyanin, namely binding with pigment, and its involvement in L. vannamei shell colour change. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Discovery of drugs that possess activity against feline leukemia virus.
Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M
2012-04-01
Feline leukemia virus (FeLV) is a gammaretrovirus that is a significant cause of neoplastic-related disorders affecting cats worldwide. Treatment options for FeLV are limited, associated with serious side effects, and can be cost-prohibitive. The development of drugs used to treat a related retrovirus, human immunodeficiency virus type 1 (HIV-1), has been rapid, leading to the approval of five drug classes. Although structural differences affect the susceptibility of gammaretroviruses to anti-HIV drugs, the similarities in mechanism of replication suggest that some anti-HIV-1 drugs may also inhibit FeLV. This study demonstrates the anti-FeLV activity of four drugs approved by the US FDA (Food and Drug Administration) at non-toxic concentrations. Of these, tenofovir and raltegravir are anti-HIV-1 drugs, while decitabine and gemcitabine are approved to treat myelodysplastic syndromes and pancreatic cancer, respectively, but also have anti-HIV-1 activity in cell culture. Our results indicate that these drugs may be useful for FeLV treatment and should be investigated for mechanism of action and suitability for veterinary use.
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Hoekstra, R; de Vos, F Y F L; Eskens, F A L M; de Vries, E G E; Uges, D R A; Knight, R; Carr, R A; Humerickhouse, R; Verweij, J; Gietema, J A
2006-03-01
We performed a phase I study with the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 combined with 5-fluorouracil and leucovorin (5-FU/LV) to determine safety profile and assess pharmacokinetic interactions. Patients with advanced solid malignancies received LV 20 mg/m(2) followed by 5-FU 425 mg/m(2) both administered intravenously in 15 min daily for 5 days every 4 weeks. ABT-510 was administered subcutaneously twice daily continuously from day 2 onwards. Blood and urine samples for pharmacokinetic analyses were collected at days 1, 5 and 22. Twelve patients received a total of 45 cycles of 5-FU/LV combined with ABT-510. ABT-510 dose levels studied were 50 and 100 mg. The combination was well tolerated, with a toxicity profile comparable to that of 5-FU/LV alone. At the dose levels studied no significant pharmacokinetic interactions were observed. These data indicate that ABT-510 administered twice daily subcutaneously can be safely combined with 5-FU/LV administered daily for 5 days, every 4 weeks.
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2012-01-01
Background Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method for determining left ventricular (LV) mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR. Methods Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Results Ninety-one patients (61±21 years; 57 male) with aortic stenosis (aortic valve area 0.93±0.32cm2) were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43) and pattern (P=0.22) of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02). Six patterns of LV adaption were observed: normal ventricular geometry (n=11), concentric remodeling (n=11), asymmetric remodeling (n=11), concentric hypertrophy (n=34), asymmetric hypertrophy (n=14) and LV decompensation (n=10). Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm) with hypertrophic cardiomyopathy. Conclusions We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common. Trial registration ClinicalTrials.gov Reference Number: NCT00930735 PMID:22839417
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1982-01-01
The spontaneous expression of ecotropic murine leukemia virus (MuLV) in spleen cells of BALB/c, C57BL/6 (B6), and derivative mice was examined as a function of age. The patterns of spontaneous virus induction in vivo correlate with the patterns of virus induction in vitro, which result from the action of two loci, Inc-l and Inb-l (7). Whereas mice carrying Inc-l or Inb-l have similar phenotypes in vitro, they have significantly different phenotypes in vivo. Mice of the Inb-l+/+ genotype, e.g., B6, rarely expressed MuLV, and the titer of MuLV recovered from rare MuLV-positive mice of this genotype was usually low. Mice of the Inc-l+/+ genotype, e.g., BALB/c, expressed low amounts of MuLV early in life, however, from 6-12 mo of age approximately one- half of the Inc-l+/+ mice expressed virus, frequently of high titer. Equal numbers of N-tropic and B-tropic MuLV were recovered from Inb-l+ mice, but predominantly N-tropic MuLV was recovered from Inc-l+ mice. Strains that carry dominant (+) alleles at both Inc-l and Inb-l show higher titers of MuLV earlier in life than strains that carry only Inc- l or Inb-l. The presence of dominant alleles at both loci results in the appearance of predominantly N-tropic virus early in life. These results demonstrate that the principal determinants of spontaneous virus expression in these low leukemic strains of mice are the In loci or genes linked to them. A further inference that can be drawn from these studies is that the appearance of B-tropic virus is by no means a random process but rather results from predictable patterns of MuLV expression and alteration. PMID:6284854
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Lech, Agnieszka K; Dobrowolski, Piotr P; Klisiewicz, Anna; Hoffman, Piotr
2017-01-01
The management of patients with asymptomatic severe aortic stenosis (ASAS) is still under discussion. Therefore, it is advisable to search for the parameters of early damage to left ventricular (LV) function. The aim of the study was to assess exercise-induced changes in LV global longitudinal strain (GLS) in ASAS. The ASAS group consisted of 50 patients (26 women and 24 men, aged 38.4 ± 18.1 years) meeting the echocardiographic criteria of severe aortic stenosis (AVA < 1 cm², AVAI < 0.6 cm²/m², Vmax > 4 m/s, mean aortic gradient > 40 mm Hg), with normal LV ejection fraction (LVEF ≥ 55%) and sinus rhythm on electrocardiogram, and without significant concomitant valvular heart diseases. The control group consisted of 21 people matched for age and sex. Echocardiographic examinations and echocardiographic stress tests with the assessment of GLS using the speckle tracking imaging were performed. The ASAS group was characterised by statistically significantly higher LV mass index (LVMI) and higher LVEF. GLS values at rest in both groups were within normal limits but were significantly higher in the control group (-18.9 ± 2.4% vs. -20.7 ± 1.7%, p = 0.006). An increase in GLS at peak exercise in both groups was observed, lower in the ASAS group (the difference was not statistically significant: -0.8 ± 3.0% vs. -2.2 ± 3.1%, p = 0.086). Changes in GLS during exercise (ΔGLS) did not correlate with the parameters of the severity of aortic stenosis. In the multivariate model, LVMI proved to be a factor associated with GLS at rest and during exercise. In patients with ASAS, GLS is a non-invasive marker of an early stage of LV myocardial damage associated with myocardial hypertrophy. An increase in GLS during exercise in the ASAS group, smaller than in the control group, indicates a preserved functional reserve of the LV myocardium but smaller than in healthy individuals. The assessment of the clinical usefulness of exercise-induced changes in GLS requires further research.
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Barros-Gomes, Sergio; Naksuk, Niyada; Jevremovic, Dragan
2017-01-01
Cardiac amyloidosis (CA) is relatively rare and frequently misdiagnosed. Other disorders presenting with increased left ventricular (LV) mass can mimic its diagnosis. This case illustrates unique findings of primary light chain (AL) amyloidosis in a patient with remarkable signs of CA. Here, we report a 49-year-old male with prior diagnosis of hypertrophic cardiomyopathy (HCM) based on an echocardiogram performed 1 year earlier, which presented with 8 weeks of periorbital rash. The patient had numbness in the past 3 years. More recently, the patient presented with shortness of breath. Physical examination was remarkable for periorbital purpura, macroglossia and orthostatic hypotension. Cardiac auscultation showed S3 and S4. Electrocardiography showed diffuse low-voltage QRS complexes. Echocardiography revealed severe diastolic impairment; granular ‘sparkling’ pattern of the myocardium with thickened walls, interatrial septum and valves; and pericardial effusion. Diastolic dysfunction and thick walls with low ECG voltage are compelling diagnostic findings. Laboratory workup showed increased free light chain-differential (FLC-diff), N-terminal fragment of brain natriuretic peptide (NT-BNP) and cardiac Troponin T (cTnT). Bone marrow biopsy confirmed AL amyloidosis. A diagnosis of AL amyloidosis with cardiac involvement mimicking HCM was made. The patient died during hospitalization due to sudden cardiac death. This case illustrates the importance of the combination of clinical, serological, and electro- and echocardiographic findings to establish the diagnosis of CA. Learning points: Several disorders presenting with increased LV mass can mimic CA. Echocardiography is one of the most important methods to diagnose CA and HCM. Signs of CA include LV wall thickness; thickening of interatrial septum, valves and right ventricular free wall; and pericardial effusion. Diastolic dysfunction and thick walls on echocardiography with low ECG voltage are the hallmark of disease. CA is a major prognostic factor in AL amyloidosis. Signs of HCM on echocardiography include several patterns of LV hypertrophy, such as sigmoidal, reverse curve, neutral and apical morphologies; LV outflow tract or mid-cavity obstruction; systolic anterior motion of mitral leaflets; mitral regurgitation and diastolic dysfunction. The combination of clinical and serological features, along morphological and functional structures, has an important role for establishing diagnosis and predicting prognosis. PMID:28687586
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von Knobelsdorff-Brenkenhoff, Florian; Karunaharamoorthy, Achudhan; Trauzeddel, Ralf Felix; Barker, Alex J; Blaszczyk, Edyta; Markl, Michael; Schulz-Menger, Jeanette
2016-01-01
Background Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. Study aim was to describe blood flow patterns in the ascending aorta of AS patients and determine their association with remodeling. Methods and Results Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age 63±13 years) and 37 healthy controls (age 60±10 years) underwent 4D-flow MRI. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress (WSSpeak) in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index (LVMI-I) and the ratio of LV mass to enddiastolic volume (relative wall mass; RWM). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and AS patients exhibited an asymmetric and elevated distribution of WSSpeak. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (p=0.0274), eccentricity (p=0.0070) and flow displacement (p=0.0021). Bicuspid aortic valve was associated with more intense helical (p=0.0098) and vortical flow formation (p=0.0536), higher flow displacement (p=0.11) and higher WSSpeak (p=0.0926). LVM-I and RWM were significantly associated with aortic orifice area (p=0.0611, p=0.0058) and flow displacement (p=0.0058, p=0.0283). Conclusions In this pilot study, AS leads to abnormal blood flow pattern and WSSpeak in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling. PMID:26917824
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Dermal Filler Injection: A Novel Approach for Limiting Infarct Expansion
Ryan, Liam P.; Matsuzaki, Kanji; Noma, Mio; Jackson, Benjamin M.; Eperjesi, Thomas J.; Plappert, Theodore J.; St. John-Sutton, Martin G.; Gorman, Joseph H.; Gorman, Robert C.
2011-01-01
Background Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling. Methods Fifteen sheep were subjected to an anteroapical MI involving approximately 20% of the LV followed by the injection of 1.3 mL of a calcium hydroxyapatite–based dermal filler into the infarct. Real-time three-dimensional echocardiography was performed at baseline, 30 minutes after MI, and 15 minutes after injection to assess infarct expansion. Sixteen additional sheep were subjected to the same infarction and followed echocardiographically and hemodynamically for 4 weeks after MI to assess chronic remodeling. Eight animals had injection with dermal filler as described above immediately after MI, and 8 animals were injected with an equal amount of saline solution. Results All animals exhibited infarct expansion soon after coronary occlusion. The regional ejection fraction of the apex became negative after infarction, consistent with systolic dyskinesia. Injection of the dermal filler converted the apical wall motion from dyskinetic to akinetic and resulted immediately in significant decreases in global, regional, and segmental LV volumes. Chronically, relative to saline control, dermal filler injection significantly reduced LV end-systolic volume (62.2 ± 3.6 mL versus 44.5 ± 3.9 mL; p < 0.05) and improved global ejection fraction (0.295 ± 0.016 versus 0.373 ± 0.017; p < 0.05) at 4 weeks after infarction. Conclusions Injection of an acellular dermal filler into an MI immediately after coronary occlusion reduces early infarct expansion and limits chronic LV remodeling. PMID:19101288
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Karamitsos, Theodoros D; Hudsmith, Lucy E; Selvanayagam, Joseph B; Neubauer, Stefan; Francis, Jane M
2007-01-01
Accurate and reproducible measurement of left ventricular (LV) mass and function is a significant strength of Cardiovascular Magnetic Resonance (CMR). Reproducibility and accuracy of these measurements is usually reported between experienced operators. However, an increasing number of inexperienced operators are now training in CMR and are involved in post-processing analysis. The aim of the study was to assess the interobserver variability of the manual planimetry of LV contours amongst two experienced and six inexperienced operators before and after a two months training period. Ten healthy normal volunteers (5 men, mean age 34+/-14 years) comprised the study population. LV volumes, mass, and ejection fraction were manually evaluated using Argus software (Siemens Medical Solutions, Erlangen, Germany) for each subject, once by the two experienced and twice by the six inexperienced operators. The mean values of experienced operators were considered the reference values. The agreement between operators was evaluated by means of Bland-Altman analysis. Training involved standardized data acquisition, simulated off-line analysis and mentoring. The trainee operators demonstrated improvement in the measurement of all the parameters compared to the experienced operators. The mean ejection fraction variability improved from 7.2% before training to 3.7% after training (p=0.03). The parameter in which the trainees showed the least improvement was LV mass (from 7.7% to 6.7% after training). The basal slice selection and contour definition were the main sources of errors. An intensive two month training period significantly improved the accuracy of LV functional measurements. Adequate training of new CMR operators is of paramount importance in our aim to maintain the accuracy and high reproducibility of CMR in LV function analysis.
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Alluri, Ram; Jakus, Adam; Bougioukli, Sofia; Pannell, William; Sugiyama, Osamu; Tang, Amy; Shah, Ramille; Lieberman, Jay R
2018-04-01
The purpose of this study was to evaluate the viability of human adipose-derived stem cells (ADSCs) transduced with a lentiviral (LV) vector to overexpress bone morphogenetic protein-2 (BMP-2) loaded onto a novel 3D printed scaffold. Human ADSCs were transduced with a LV vector carrying the cDNA for BMP-2. The transduced cells were loaded onto a 3D printed Hyperelastic "Bone" (HB) scaffold. In vitro BMP-2 production was assessed using enzyme-linked immunosorbent assay analysis. The ability of ADSCs loaded on the HB scaffold to induce in vivo bone formation in a hind limb muscle pouch model was assessed in the following groups: ADSCs transduced with LV-BMP-2, LV-green fluorescent protein, ADSCs alone, and empty HB scaffolds. Bone formation was assessed using radiographs, histology and histomorphometry. Transduced ADSCs BMP-2 production on the HB scaffold at 24 hours was similar on 3D printed HB scaffolds versus control wells with transduced cells alone, and continued to increase after 1 and 2 weeks of culture. Bone formation was noted in LV-BMP-2 animals on plain radiographs at 2 and 4 weeks after implantation; no bone formation was noted in the other groups. Histology demonstrated that the LV-BMP-2 group was the only group that formed woven bone and the mean bone area/tissue area was significantly greater when compared with the other groups. 3D printed HB scaffolds are effective carriers for transduced ADSCs to promote bone repair. The combination of gene therapy and tissue engineered scaffolds is a promising multidisciplinary approach to bone repair with significant clinical potential. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1104-1110, 2018. © 2018 Wiley Periodicals, Inc.
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Bodetoft, Stefan; Carlsson, Marcus; Arheden, Håkan; Ekelund, Ulf
2011-02-01
Oxygen (O2) is a cornerstone in the treatment of critically ill patients, and the guidelines prescribe 10-15 l of O2/min even to those who are initially normoxic. Studies using indirect or invasive methods suggest, however, that supplemental O2 may have negative cardiovascular effects. The aim of this study was to test the hypothesis, using noninvasive cardiac magnetic resonance imaging, that inhaled supplemental O2 decreases cardiac output (CO) and coronary blood flow in healthy individuals. Sixteen healthy individuals inhaled O2 at 1, 8 and 15 l/min through a standard reservoir bag mask. A 1.5 T magnetic resonance imaging scanner was used to measure stroke volume, CO and coronary sinus blood flow. Left ventricular (LV) perfusion was calculated as coronary sinus blood flow/LV mass. The O2 response was dose-dependent. At 15 l of O2/min, blood partial pressure of O2 increased from an average 11.7 to 51.0 kPa with no significant changes in blood partial pressure of CO2 or arterial blood pressure. At the same dose, LV perfusion decreased by 23% (P=0.005) and CO decreased by 10% (P=0.003) owing to a decrease in heart rate (by 9%, P<0.002), with no significant changes in stroke volume or LV dimensions. Owing to the decreased CO and LV perfusion, systemic and coronary O2 delivery fell by 4 and 11% at 8 l of O2/min, despite the increased blood oxygen content. Our data indicate that O2 administration decreases CO, LV perfusion and systemic and coronary O2 delivery in healthy individuals. Further research should address the effects of O2 therapy in normoxic patients.
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Peterson, Vernice R; Norton, Gavin R; Redelinghuys, Michelle; Libhaber, Carlos D; Maseko, Muzi J; Majane, Olebogeng H I; Brooksbank, Richard; Woodiwiss, Angela J
2015-05-01
Whether left ventricular (LV) geometric remodeling, as indexed by relative wall thickness (RWT), aggregates in families and is inherited independent of LV mass (LVM) and additional confounders is uncertain. We determined whether RWT as assessed from 2D targeted M-mode echocardiography shows intrafamilial aggregation and heritability independent of LVM in 181 nuclear families (73 spouse pairs, 403 parent-child pairs, and 177 sibling-sibling pairs) with 16 families including 3 generations from an urban developing community of black Africans. Intrafamilial aggregation and heritability estimates (S.A.G.E. software) were assessed independent of confounders, including central aortic systolic blood pressure (SBPc) (radial applanation tonometry and SphygmoCor software). Independent of confounders including SBPc, LV RWT was correlated in parent-child (r = 0.32, P < 0.0001) and sibling-sibling (r = 0.29, P < 0.0001), but not in spouse (r = 0.11, P = 0.33) pairs. The relationships between parent-child (r = 0.28, P < 0.0001) and sibling-sibling (r = 0.24, P < 0.001) pairs persisted with further adjustments for LVM or LVM indexed to height(2.7) (LVMI). Similarly, independent of confounders, LV RWT showed significant heritability (h(2) ± SEM = 0.56 ± 0.09, P < 0.0001) and this persisted with further adjustments for LVM (h(2) ± SEM = 0.48 ± 0.09, P < 0.0001) or LVMI (h(2) ± SEM = 0.49 ± 0.09, P < 0.0001). In a group of African ancestry, independent of LVM, LV geometric remodeling shows significant intrafamilial aggregation and heritability. Genetic factors may in-part determine the LV geometric remodeling process independent of the extent of cardiac hypertrophy. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Left ventricular geometry in children and adolescents with primary hypertension
Richey, Phyllis A.; DiSessa, Thomas G.; Somes, Grant W.; Alpert, Bruce S.; Jones, Deborah P.
2009-01-01
Objective Children with hypertension (HTN) are at increased risk for left ventricular hypertrophy (LVH). Increased LV mass by the process of remodeling in response to volume or pressure loading may be eccentric (increased LV diameter) or concentric (increased wall thickness). Our objective was to classify LV geometry among children with primary HTN and examine differences in ambulatory blood pressure (ABP). Study design Subjects aged 7-18 years with suspected HTN were enrolled in this cross-sectional study. ABP and LVM index (LVMI) and were measured within the same 24 hour period. LV geometry was classified as normal, concentric remodeling, concentric LVH or eccentric LVH. Results Children with LVH had significantly higher ambulatory systolic and diastolic BP levels and BMI z-score. Sixty-eight children had HTN based upon ABPM. Thirty-eight percent of the hypertensive subjects had LVH, with equal distribution in the concentric and eccentric groups. There were significant differences in the 24-hour diastolic BP (DBP) parameters when the eccentric LVH group was compared to the normal geometry and concentric LVH groups. Relative wall thickness was inversely associated with nighttime DBP parameters. These relationships persisted after controlling for BMI Z-score. Conclusions While the risk for LVH is associated with increased systolic BP and BMI Z-score, those with eccentric LVH had significantly higher DBP. PMID:19851297
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NASA Technical Reports Server (NTRS)
Bauer, Fabrice; Jones, Michael; Shiota, Takahiro; Firstenberg, Michael S.; Qin, Jian Xin; Tsujino, Hiroyuki; Kim, Yong Jin; Sitges, Marta; Cardon, Lisa A.; Zetts, Arthur D.;
2002-01-01
OBJECTIVE: The goal of this study was to analyze left ventricular outflow tract systolic acceleration (LVOT(Acc)) during alterations in left ventricular (LV) contractility and LV filling. BACKGROUND: Most indexes described to quantify LV systolic function, such as LV ejection fraction and cardiac output, are dependent on loading conditions. METHODS: In 18 sheep (4 normal, 6 with aortic regurgitation, and 8 with old myocardial infarction), blood flow velocities through the LVOT were recorded using conventional pulsed Doppler. The LVOT(Acc) was calculated as the aortic peak velocity divided by the time to peak flow; LVOT(Acc) was compared with LV maximal elastance (E(m)) acquired by conductance catheter under different loading conditions, including volume and pressure overload during an acute coronary occlusion (n = 10). In addition, a clinically validated lumped-parameter numerical model of the cardiovascular system was used to support our findings. RESULTS: Left ventricular E(m) and LVOT(Acc) decreased during ischemia (1.67 +/- 0.67 mm Hg.ml(-1) before vs. 0.93 +/- 0.41 mm Hg.ml(-1) during acute coronary occlusion [p < 0.05] and 7.9 +/- 3.1 m.s(-2) before vs. 4.4 +/- 1.0 m.s(-2) during coronary occlusion [p < 0.05], respectively). Left ventricular outflow tract systolic acceleration showed a strong linear correlation with LV E(m) (y = 3.84x + 1.87, r = 0.85, p < 0.001). Similar findings were obtained with the numerical modeling, which demonstrated a strong correlation between predicted and actual LV E(m) (predicted = 0.98 [actual] -0.01, r = 0.86). By analysis of variance, there was no statistically significant difference in LVOT(Acc) under different loading conditions. CONCLUSIONS: For a variety of hemodynamic conditions, LVOT(Acc) was linearly related to the LV contractility index LV E(m) and was independent of loading conditions. These findings were consistent with numerical modeling. Thus, this Doppler index may serve as a good noninvasive index of LV contractility.
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Lin, Yong-Chin; Chen, Jiann-Chu; Chen, Yu-Yuan; Liu, Chun-Hung; Cheng, Winton; Hsu, Chih-Hung; Tsui, Wen-Ching
2013-06-01
The full sequence of white shrimp Litopenaeus vannamei integrin β (LV-B) is 2879bp which encodes 787 amino acids (aa) of the open reading frame (ORF). The mature protein (764 aa) contains (1) an extracellular domain (ED) of 692 aa, (2) a transmembrane domain (TD) of 23 aa, and (3) a cytoplasmic domain (CD) of 49 aa. The cloned LV-B grouped together with crayfish Pacifastacus leniusculus integrin β (PL-B1), but was far away from vertebrate integrin β1, β3, β5, β6, β7, and β8, and another L. vannamei integrin β (LV). A Southern blot analysis indicated that the cloned LV-B was a single copy of genomic DNA. LV-B mRNA was expressed in all tissues, and was highly expressed in haemocytes. LV-B was downregulated in shrimp 24 and 96h after having received white spot syndrome virus (WSSV). LV-B expression by haemocytes of shrimp was higher in the postmoult (A and B) stage, and lower in the premoult (D2/D3) stage. LV-B expression was significantly higher by shrimp reared in 2.5‰ and 5‰ salinities. Shrimp injected with integrin β dsRNA showed gene silencing of integrin β after 36h. LV-B-silenced shrimp showed decreased hyaline cells (HCs), granular cells (GCs, including semi-granular cells), the total haemocyte count (THC), respiratory bursts (RBs), and lysozyme activity, but showed increased RB/HC, superoxide dismutase (SOD) activity/HC, and the phenoloxidase (PO) activity/GC. LV-B-silenced shrimp showed upregulated expressions of lipopolysaccharide- and β-glucan-binding protein (LGBP), peroxinectin (PX), prophenoloxidase I (proPO I), proPO II, proPO-activating enzyme (ppA), α2-macroglobulin (α2-M), cytMnSOD, mtMnSOD, and heat shock protein 70 (HSP70). It was concluded that integrin β plays important roles in proPO activation, phagocytosis, and the antioxidant system for immunomodulation in shrimp. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Yamazaki, J; Naitou, K; Ishida, S; Uno, N; Saisho, K; Munakata, T; Morishita, T; Takano, M; Yabe, Y
1997-05-01
To evaluate left ventricular (LV) wall motion stereoscopically from all directions and to calculate the LV volume by three-dimensional (3D) imaging. 99mTc-DTPA human serum albumin-multigated cardiac pool-single photon emission computed tomography (99mTc-MUGA-SPECT) was performed. A new data processing program was developed with the Application Visualization System-Medical Viewer (AVS-MV) based on images obtained from 99mTc-MUGA-SPECT. In patients with previous myocardial infarction, LV function and LV wall motion were evaluated by 3D-99mTc-MUGA imaging. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were obtained from 3D-99mTc-MUGA images by the surface rendering method, and the left ventricular ejection fraction (LVEF) was calculated at thresholds of 35% (T1), 40% (T2), 45% (T3), and 50% (T4). There was a strong correlation between the LV volume calculated by 3D-99mTc-MUGA imaging at a threshold of 40% and that determined by contrast left ventriculography (LVEDV: 194.7 +/- 36.0 ml vs. 198.7 +/- 39.1 ml, r = 0.791, p < 0.001; LVESV: 91.6 +/- 44.5 ml vs. 93.3 +/- 41.3 ml, r = 0.953, p < 0.001), respectively. When compared with the LVEF data obtained by left ventriculography, significant correlations were found for 3D images reconstructed at each threshold (T1: r = 0.966; T2: r = 0.962; T3: r = 0.958; and T4: r = 0.955). In addition, when LV wall motion obtained by 3D-99mTc-MUGA imaging (LAT and LAO views) was compared with the results obtained by left ventriculography (RAO and LAO views), there was good agreement. 3D-99mTc-MUGA imaging was superior in allowing evaluation of LV wall motion in all directions and in assessment of LV function, since data acquisition and image reconstruction could be done within a short time with the three-detector imaging system and AVS-MV. This method appears to be very useful for the observation of both LV wall motion and LV function in patients with ischemic heart disease, because it is a noninvasive examination.
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Effect of fetal hypoxia on heart susceptibility to ischemia and reperfusion injury in the adult rat.
Li, Guohu; Xiao, Yuhui; Estrella, Jaymie L; Ducsay, Charles A; Gilbert, Raymond D; Zhang, Lubo
2003-07-01
Epidemiologic studies showed an association between adverse intrauterine environment and ischemic heart disease in the adult. We tested the hypothesis that prenatal hypoxia increased the susceptibility of adult heart to ischemia-reperfusion (I-R) injury. Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% oxygen from day 15 to 21) groups. Hearts of 6-month-old male progeny were studied using Langendorff preparation and were subjected to two protocols of I-R: 10 minutes of ischemia and 3 hours of reperfusion (I-R(10)) or 25 minutes of ischemia and 3 hours of reperfusion (I-R(25)). Prenatal hypoxia did not change basal left ventricular (LV) function. I-R(10) produced myocardial stunning and a transient decrease in LV function in control hearts but caused myocardial infarction and a persistent decrease in postischemic recovery of LV function in hypoxic hearts. I-R(25) caused myocardial infarction in both control and hypoxic hearts, which was significantly higher in hypoxic hearts. The postischemic recovery of LV function was significantly reduced in hypoxic hearts. I-R(25)-induced activation of caspase-3 and apoptosis in the left ventricle were significantly higher in hypoxic than control hearts. There was a significant decrease in LV heat shock protein 70 and endothelial nitric oxide synthase levels in hypoxic hearts. Prenatal hypoxia did not change beta(1)-adrenoreceptor levels but significantly increased beta(2)-adrenoreceptor in the left ventricle. In addition, it increased G(s)alpha but decreased G(i)alpha. Prenatal chronic hypoxia increases the susceptibility of adult heart to I-R injury. Several possible mechanisms may be involved, including an increase in beta(2)-adrenoreceptor and the G(s)alpha/G(i)alpha ratio, and a decrease in heat shock protein 70 and endothelial nitric oxide synthase in the left ventricle.
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Fitness in Young Adulthood and Long-Term Cardiac Structure and Function: The CARDIA Study.
Pandey, Ambarish; Allen, Norrina B; Ayers, Colby; Reis, Jared P; Moreira, Henrique T; Sidney, Stephen; Rana, Jamal S; Jacobs, David R; Chow, Lisa S; de Lemos, James A; Carnethon, Mercedes; Berry, Jarett D
2017-05-01
This study sought to evaluate the association between early-life cardiorespiratory fitness (CRF) and measures of left ventricular (LV) structure and function in midlife. Low CRF in midlife is associated with a higher risk of heart failure. However, the unique contributions of early-life CRF toward measures of LV structure and function in middle age are not known. CARDIA (Coronary Artery Risk Development in Young Adults) study participants with a baseline maximal treadmill test and an echocardiogram at year 25 were included. Associations among baseline CRF, CRF change, and echocardiographic LV parameters (global longitudinal strain [GLS] and global circumferential strain, E/e') were assessed using multivariable linear regression. The study included 3,433 participants. After adjustment for baseline demographic and clinical characteristics, lower baseline CRF was significantly associated with higher LV strain (standardized parameter estimate [Std β] = -0.06; p = 0.03 for GLS) and ratio of early transmitral flow velocity to early peak diastolic mitral annular velocity (E/e') (Std β = -0.10; p = 0.0001 for lateral E/e'), findings suggesting impaired contractility and elevated diastolic filling pressure in midlife. After additional adjustment for cumulative cardiovascular risk factor burden observed over the follow-up period, the association of CRF with LV strain attenuated substantially (p = 0.36), whereas the association with diastolic filling pressure remained significant (Std β = -0.05; p = 0.02 for lateral E/e'). In a subgroup of participants with repeat CRF tests at year 20, greater decline in CRF was significantly associated with increased abnormalities in GLS (Std β = -0.05; p = 0.02) and higher diastolic filling pressure (Std β = -0.06; p = 0.006 for lateral E/e') in middle age. CRF in young adulthood and CRF change were associated with measures of LV systolic function and diastolic filling pressure in middle age. Low CRF-associated abnormalities in systolic function were related to the associated higher cardiovascular risk factor burden. In contrast, the inverse association between CRF and LV diastolic filling pressure was independent of cardiovascular risk factor burden. Copyright © 2017. Published by Elsevier Inc.
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Piorkowski, Christopher; Breithardt, Ole-A; Razavi, Hedi; Nabutovsky, Yelena; Rosenberg, Stuart P; Markovitz, Craig D; Arya, Arash; Rolf, Sascha; John, Silke; Kosiuk, Jedrzej; Olson, Eric; Eitel, Charlotte; Huo, Yan; Döring, Michael; Richter, Sergio; Ryu, Kyungmoo; Gaspar, Thomas; Prinzen, Frits W; Hindricks, Gerhard; Sommer, Philipp
2017-10-01
In times of evolving cardiac resynchronization therapy, intra-procedural characterization of left ventricular (LV) mechanical activation patterns is desired but technically challenging with currently available technologies. In patients with normal systolic function, we evaluated the feasibility of characterizing LV wall motion using a novel sensor-based, real-time tracking technology. Ten patients underwent simultaneous motion and electrical mapping of the LV endocardium during sinus rhythm using electroanatomical mapping and navigational systems (EnSite™ NavX™ and MediGuide™, SJM). Epicardial motion data were also collected simultaneously at corresponding locations from accessible coronary sinus branches. Displacements at each mapping point and times of electrical and mechanical activation were combined over each of the six standard LV wall segments. Mechanical activation timing was compared with that from electrical activation and preoperative 2D speckle tracking echocardiography (echo). MediGuide-based displacement data were further analysed to estimate LV chamber volumes that were compared with echo and magnetic resonance imaging (MRI). The lateral and septal walls exhibited the largest (12.5 [11.6-15.0] mm) and smallest (10.2 [9.0-11.3] mm) displacement, respectively. Radial displacement was significantly larger endocardially than epicardially (endo: 6.7 [5.0-9.1] mm; epi: 3.8 [2.4-5.6] mm), while longitudinal displacement was significantly larger epicardially (endo: 8.0 [5.0-10.6] mm; epi: 10.3 [7.4-13.8] mm). Most often, the anteroseptal/anterior and lateral walls showed the earliest and latest mechanical activations, respectively. 9/10 patients had concordant or adjacent wall segments of latest mechanical and electrical activation, and 6/10 patients had concordant or adjacent wall segments of latest mechanical activation as measured by MediGuide and echo. MediGuide's LV chamber volumes were significantly correlated with MRI (R2= 0.73, P < 0.01) and echo (R2= 0.75, P < 0.001). The feasibility of mapping-guided intra-procedural characterization of LV wall motion was established. http://www.clinicaltrials.gov; Unique identifier: CT01629160. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
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Alter, P; Rupp, H; Rominger, M B; Klose, K J; Maisch, B
2008-01-01
In experimental animals, cardiac work is derived from pressure-volume area and analyzed further using stress-length relations. Lack of methods for determining accurately myocardial mass has until now prevented the use of stress-length relations in patients. We hypothesized, therefore, that not only pressure-volume loops but also stress-length diagrams can be derived from cardiac volume and cardiac mass as assessed by cardiac magnetic resonance imaging (CMR) and invasively measured pressure. Left ventricular (LV) volume and myocardial mass were assessed in seven patients with aortic valve stenosis (AS), eight with dilated cardiomyopathy (DCM), and eight controls using electrocardiogram (ECG)-gated CMR. LV pressure was measured invasively. Pressure-volume curves were calculated based on ECG triggering. Stroke work was assessed as area within the pressure-volume loop. LV wall stress was calculated using a thick-wall sphere model. Similarly, stress-length loops were calculated to quantify stress-length-based work. Taking the LV geometry into account, the normalization with regard to ventricular circumference resulted in "myocardial work." Patients with AS (valve area 0.73+/-0.18 cm(2)) exhibited an increased LV myocardial mass when compared with controls (P<0.05). LV wall stress was increased in DCM but not in AS. Stroke work of AS was unchanged when compared with controls (0.539+/-0.272 vs 0.621+/-0.138 Nm, not significant), whereas DCM exhibited a significant depression (0.367+/-0.157 Nm, P<0.05). Myocardial work was significantly reduced in both AS and DCM when compared with controls (129.8+/-69.6, 200.6+/-80.1, 332.2+/-89.6 Nm/m(2), P<0.05), also after normalization (7.40+/-5.07, 6.27+/-3.20, 14.6+/-4.07 Nm/m(2), P<0.001). It is feasible to obtain LV pressure-volume and stress-length diagrams in patients based on the present novel methodological approach of using CMR and invasive pressure measurement. Myocardial work was reduced in patients with DCM and noteworthy also in AS, while stroke work was reduced in DCM only. Most likely, deterioration of myocardial work is crucial for the prognosis. It is suggested to include these basic physiological procedures in the clinical assessment of the pump function of the heart.
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Giallauria, Francesco; Cirillo, Plinio; Lucci, Rosa; Pacileo, Mario; De Lorenzo, Anna; D'Agostino, Mariantonietta; Moschella, Sabino; Psaroudaki, Marianna; Del Forno, Domenico; Orio, Francesco; Vitale, Dino Franco; Chiariello, Massimo; Vigorito, Carlo
2008-02-01
To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.
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Nakayama, Tomohiro; Nishijima, Yoshinori; Miyamoto, Mutsumi; Hamlin, Robert L
2007-01-01
There have been few trials in which dogs with mitral regurgitation (MR) have been treated with various cardioactive drugs to determine effects on left ventricular (LV) function. Four classes of cardiovascular drugs may improve LV function in dogs with MR without increasing MR. Nine mature dogs were included in the study. MR was produced in 9 dogs. Five months later under butorphanol narcosis, parameters of LV function and left atrial dimension (LAD) were monitored by LV micromanometry and echocardiography/Doppler. Dogs were given (in random order) enalaprilat, nitroglycerine, ouabain, milrinone, and placebo. Nitroglycerin produced no significant change; milrinone and ouabain increased contractility; ouabain decreased heart rate; and there was evidence that enalaprilat and milrinone decreased LAD. Milrinone and ouabain decreased isovolumetric contraction time and therefore the time available for MR. There was no evidence that a positive inotrope increased MR despite increasing LV contractility and stroke volume. This study contradicts the hypotheses that (1) strengthening the left ventricle may increase MR and (2) treatment of MR (even before symptoms of heart failure develop) may decrease LAD. It is reasonable that strengthening the force of LV contraction should increase the driving pressure for MR; however, this effect did not appear to increase MR. Although some investigators believe that treating dogs with MR with afterload reducers and decreasing hindrance to ejection of blood from the LV to aorta may lengthen life by decreasing MR, there did not appear to be a reduction in MR, at least in response to the angiotensin-converting enzyme (ACE) inhibitor.
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Left atrial strain: a new parameter for assessment of left ventricular filling pressure.
Cameli, Matteo; Mandoli, Giulia Elena; Loiacono, Ferdinando; Dini, Frank Lloyd; Henein, Michael; Mondillo, Sergio
2016-01-01
In order to obtain accurate diagnosis, treatment and prognostication in many cardiac conditions, there is a need for assessment of left ventricular (LV) filling pressure. While systole depends on ejection function of LV, diastole and its disturbances influence filling function and pressures. The commonest condition that represents the latter is heart failure with preserved ejection fraction in which LV ejection is maintained, but diastole is disturbed and hence filling pressures are raised. Significant diastolic dysfunction results in raised LV end-diastolic pressure, mean left atrial (LA) pressure and pulmonary capillary wedge pressure, all referred to as LV filling pressures. Left and right heart catheterization has traditionally been used as the gold standard investigation for assessing these pressures. More recently, Doppler echocardiography has taken over such application because of its noninvasive nature and for being patient friendly. A number of indices are used to achieve accurate assessment of filling pressures including: LV pulsed-wave filling velocities (E/A ratio, E wave deceleration time), pulmonary venous flow (S wave and D wave), tissue Doppler imaging (E' wave and E/E' ratio) and LA volume index. LA longitudinal strain derived from speckle tracking echocardiography (STE) is also sensitive in estimating intracavitary pressures. It is angle-independent, thus overcomes Doppler limitations and provides highly reproducible measures of LA deformation. This review examines the application of various Doppler echocardiographic techniques in assessing LV filling pressures, in particular the emerging role of STE in assessing LA pressures in various conditions, e.g., HF, arterial hypertension and atrial fibrillation.
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Marginal donors: can older donor hearts tolerate prolonged cold ischemic storage?
Korkmaz, Sevil; Bährle-Szabó, Susanne; Loganathan, Sivakkanan; Li, Shiliang; Karck, Matthias; Szabó, Gábor
2013-10-01
Both advanced donor age and prolonged ischemic time are significant risk factors for the 1-year mortality. However, its functional consequences have not been fully evaluated in the early-phase after transplantation; even early graft dysfunction is the main determinant of long-term outcome following transplantation. We evaluated in vivo left-ventricular (LV) cardiac and coronary vascular function of old-donor grafts after short and prolonged cold ischemic times in rats 1 h after heart transplantation. The hearts were excised from young donor (3-month-old) or old donor (18-month-old) rats, stored in cold preservation solution for either 1 or 8 h, and heterotopically transplanted. After 1 h of ischemic period, in the old-donor group, LV pressure, maximum pressure development (dP/dt max), time constant of LV pressure decay (τ), LV end-diastolic pressure and coronary blood flow did not differ compared with young donors. However, endothelium-dependent vasodilatation to acetylcholine resulted in a significantly lower response of coronary blood flow in the old-donor group (33 ± 4 vs. 51 ± 15 %, p < 0.05). After 8 h preservation, two of the old-donor hearts showed no mechanical activity upon reperfusion. LV pressure (55 ± 6 vs. 72 ± 5 mmHg, p < 0.05), dP/dt max (899 ± 221 vs. 1530 ± 217 mmHg/s, p < 0.05), coronary blood flow and response to acetylcholine were significantly reduced and τ was increased in the old-donor group in comparison to young controls. During the early-phase after transplantation, the ischemic tolerance of older-donor hearts is reduced after prolonged preservation time and the endothelium is more vulnerable to ischemia/reperfusion.
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Lai, Chin-Chih; Sun, Dianjianyi; Cen, Ruiqi; Wang, Jian; Li, Shengxu; Fernandez-Alonso, Camilo; Chen, Wei; Srinivasan, Sathanur R; Berenson, Gerald S
2014-10-14
Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity and LV hemodynamic variables. The aim of this study was to examine the impact of cumulative long-term burden and trends of excessive adiposity and elevated blood pressure (BP) during childhood on adulthood LVH and LV geometric remodeling patterns. This longitudinal study consisted of 1,061 adults, age 24 to 46 years, who had been examined 4 or more times for body mass index (BMI) and BP starting in childhood, with a mean follow-up of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Four LV geometric types were defined-normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH)-all on the basis of LV mass indexed for body height (m(2.7)) and relative wall thickness. Higher values of BMI and systolic and diastolic BP in childhood and adulthood, as well as total AUC and incremental AUC, were all significantly associated with higher LV mass index and LVH, adjusted for race, sex, and age. In addition, higher values of BMI and BP in childhood and adulthood, total AUC, and incremental AUC were significantly associated with EH and CH but not with CR. Importantly, all of these measures of BMI had a consistently and significantly greater influence on EH than did measures of BP. These findings indicate that the adverse influence of excessive adiposity and elevated BP levels on LVH begins in childhood. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Nikolaidis, Lazaros A; Elahi, Dariush; Hentosz, Teresa; Doverspike, Aaron; Huerbin, Rhonda; Zourelias, Lee; Stolarski, Carol; Shen, You-tang; Shannon, Richard P
2004-08-24
The failing heart demonstrates a preference for glucose as its metabolic substrate. Whether enhancing myocardial glucose uptake favorably influences left ventricular (LV) contractile performance in heart failure remains uncertain. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with potent insulinotropic effects the action of which is attenuated when glucose levels fall below 4 mmol. We examined the impact of recombinant GLP-1 (rGLP-1) on LV and systemic hemodynamics and myocardial substrate uptake in conscious dogs with advanced dilated cardiomyopathy (DCM) as a mechanism for overcoming myocardial insulin resistance and enhancing myocardial glucose uptake. Thirty-five dogs were instrumented and studied in the fully conscious state. Advanced DCM was induced by 28 days of rapid pacing. Sixteen dogs with advanced DCM received a 48-hour infusion of rGLP-1 (1.5 pmol x kg(-1) x min(-1)). Eight dogs with DCM served as controls and received 48 hours of a saline infusion (3 mL/d). Infusion of rGLP-1 was associated with significant (P<0.02) increases in LV dP/dt (98%), stroke volume (102%), and cardiac output (57%) and significant decreases in LV end-diastolic pressure, heart rate, and systemic vascular resistance. rGLP-1 increased myocardial insulin sensitivity and myocardial glucose uptake. There were no significant changes in the saline control group. rGLP-1 dramatically improved LV and systemic hemodynamics in conscious dogs with advanced DCM induced by rapid pacing. rGLP-1 has insulinomimetic and glucagonostatic properties, with resultant increases in myocardial glucose uptake. rGLP-1 may be a useful metabolic adjuvant in decompensated heart failure.
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Sleep Duration and Quality as Related to Left Ventricular Structure and Function.
Lee, Jae-Hon; Park, Sung Keun; Ryoo, Jae-Hong; Oh, Chang-Mo; Kang, Jeong Gyu; Mansur, Rodrigo B; Alfonsi, Jeffrey E; Lee, Yena; Shin, Sun-Han; McIntyre, Roger S; Jung, Ju Young
2018-01-01
Inadequate sleep is associated with increased risk of cardiovascular events; however, the associations between sleep duration or quality and cardiac function or structure are not well understood. This cross-sectional study was conducted to investigate to what extent sleep duration and quality are associated with left ventricular (LV) diastolic dysfunction or structural deterioration. A total of 31,598 healthy Korean adults who received echocardiography and completed the Pittsburg Sleep Quality Index were enrolled in this study. Participants were stratified into three groups by self-reported sleep duration (i.e., <7, 7-9, >9 hours) and into two groups by subjective sleep quality. Sleep duration was also assessed as a continuous variable. The odds ratios for impaired LV diastolic function, increased relative wall thickness, and LV hypertrophy (LVH) were compared between groups using multivariable logistic regression analyses. After adjustment for confounding variables (e.g., age, smoking, body mass index), there was a statistically significant association between short sleep duration (<7 hours) and greater LVH (fully adjusted odds ratio = 1.32 [95% confidence interval {CI} = 1.02-1.73]). Short sleep duration was also significantly associated with greater LVH (0.87 per hour [95% CI = 0.78-0.98]) and increased relative wall thickness (0.92 [95% CI = 0.86-0.99]), but there was no significant association between sleep and LV diastolic function. Among individuals with normal sleep duration, poor quality of sleep was not associated with adverse cardiac measures. These results indicate that short sleep duration (<7 hours) is associated with unfavorable LV structural characteristics. The association of insufficient sleep with adverse cardiovascular health outcomes may be mediated in part by adverse changes in cardiac structure and function.
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Thomas, D P; McCormick, K M; Jenkins, R R
1988-01-01
The study was designed to evaluate the effects of eight weeks of exercise training or training-beta-adrenergic blockade combination on gross and microscopic alterations of rat cardiac muscle and microvascular bed. Rats were randomly assigned to either sedentary control (C), trained (T), metoprolol-trained (MT), or propranolol-trained (PT) groups. The training protocol involved treadmill running for 8 weeks at 0.5 ms-1, 20% grade. Earlier experiments by us showed this training protocol to be effective in producing significant changes in selected skeletal muscle enzyme activities in all trained groups. In the current study an absolute reduction in left ventricular (LV) weight was observed in the PT compared to the C group (0.91 +/- 0.02 vs. 1.04 +/- 0.04 g, P less than 0.05). LV weight in the T and MT groups was no different from C so that LV to BW ratio (mg.g-1) was significantly increased (P less than 0.05) due to a similar reduction in body weight (BW) in all three training groups. Morphometric analysis of LV myocardium revealed no significant differences in myocyte mean cross-sectional area (micron 2) in any of the groups (289 +/- 16-C, 332 +/- 20-T, 281 +/- 44-MT, and 273 +/- 12-PT). Capillary density independently calculated by light and electron microscopy was unchanged by training or training-beta-blockade combination. It was concluded that training of sufficient intensity and duration to produce skeletal muscle enzyme adaptations does not necessarily produce myocyte hypertrophy or alter LV capillarity. Additionally functioning beta-adrenergic receptors appear to play a role in both the central and peripheral adaptations to endurance exercise training.
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Ilić, Ivan; Djordjević, Vitomir; Stanković, Ivan; Vlahović-Stipac, Alja; Putniković, Biljana; Babić, Rade; Nesković, Aleksandar N
2014-04-01
Long-term intensive training is associated with distinctive cardiac adaptations which are known as athlete's heart. The aim of this study was to determine whether the use of anabolic androgenic steroids (AAS) could affect echocardiographic parameters of left ventricular (LV) morphology and function in elite strength and endurance athletes. A total of 20 elite strength athletes (10 AAS users and 10 non-users) were compared to 12 steroid-free endurance athletes. All the subjects underwent comprehensive standard echocardiography and tissue Doppler imaging. After being indexed for body surface area, both left atrium (LA) and LV end-diastolic diameter (LVEDD) were significantly higher in the endurance than strength athletes, regardless of AAS use (p < 0.05, for both). A significant correlation was found between LA diameter and LVEDD in the steroid-free endurance athletes, showing that 75% of LA size variability depends on variability of LVEDD (p < 0.001). No significant differences in ejection fraction and cardiac output were observed among the groups, although mildly reduced LV ejection fraction was seen only in the AAS users. The AAS-using strength athletes had higher A-peak velocity when compared to steroid-free athletes, regardless of training type (p < 0.05 for both). Both AAS-using and AAS-free strength athletes had lower e' peak velocity and higher E/e' ratio than endurance athletes (p < 0.05, for all). There is no evidence that LV ejection fraction in elite athletes is altered by either type of training or AAS misuse. Long-term endurance training is associated with preferable effects on LV diastolic function compared to strength training, particularly when the latter is combined with AAS abuse.
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The influence of night-time hypertension on left ventricular mechanics.
Tadic, Marijana; Cuspidi, Cesare; Pencic-Popovic, Biljana; Celic, Vera; Mancia, Giuseppe
2017-09-15
The aim of this study was to evaluate left ventricular (LV) mechanics in individuals with daytime, night-time and day-nighttime hypertension. This cross-sectional study included 272 untreated subjects who underwent 24-hour ambulatory blood pressure monitoring and complete two-dimensional echocardiographic examination including strain analysis. According to current guidelines, night-time hypertension was defined as nocturnal systolic blood pressure≥120mmHg and/or diastolic blood pressure≥70mmHg and day-time hypertension as systolic blood pressure≥135mmHg and/or diastolic blood pressure≥85mmHg. The study sample included 61 normotensive subjects (22%), 77 isolated daytime hypertension (28%), 40 isolated night-time hypertension (15%) and 94day-nighttime hypertension (35%). LV longitudinal and circumferential strain gradually and significantly decreased from normotensive subjects across patients with isolated daytime and night-time hypertension to hypertensive individuals with persistent hypertension. Radial strain was similar between the observed groups. LV twist increased from normotensive subjects across isolated daytime and night-time hypertensive patients to day-nighttime hypertensive individuals. Hypertensive patients with day-nighttime and night-time hypertension are significantly more associated with decreased longitudinal and circumferential strain than hypertensive patients with isolated day-time hypertension and normotension. LV mechanics gradually deteriorated from normotensive controls, across isolated day- and night-time hypertension, to day-nighttime hypertension. Patients with night-time and day-nighttime hypertension are associated with higher risk of LV mechanical dysfunction than normotensives and day-time hypertensives. Copyright © 2017 Elsevier B.V. All rights reserved.
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Peng, Dongxian; He, Yuanli
2015-02-01
To investigate the inhibitory effect of lentiviral vector-mediated short hairpin RNA targeting survivin (LV-survivin shRNA) on the growth of human endometrium xenograft in the abdominal cavity of nude mice. The endometrium xenografts from 8 women with endometriosis were injected into the peritoneal cavities of 45 nude mice. The mice were then randomly assigned to receive intraperitoneal injection of LV-survivin shRNA, pGCL-NC-GFP (negative control) or PBS (blank control). Two weeks later, the number and morphometry of endometriotic lesions were quantified and the expression of survivin protein were detected by immunohistochemistry. The formation of endometriotic lesions was significantly suppressed in mice receiving LV-survivin shRNA injection as compared with those in the two control groups (P/0.001). The mice in LV-survivin-shRNA group showed significantly down-regulated expression levels of survivin protein compared with those in the negative and blank control groups, presenting also necrosis in the endometriosis-like lesions in microscopic observation. Lentiviral vector-mediated shRNA can effectively inhibit the expression of survivin in human endometrium xengrafts and suppress the formation and growth of endometriotic lesions in the abdominal cavities of nude mice.
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Does combined strength training and local vibration improve isometric maximum force? A pilot study.
Goebel, Ruben; Haddad, Monoem; Kleinöder, Heinz; Yue, Zengyuan; Heinen, Thomas; Mester, Joachim
2017-01-01
The aim of the study was to determine whether a combination of strength training (ST) and local vibration (LV) improved the isometric maximum force of arm flexor muscles. ST was applied to the left arm of the subjects; LV was applied to the right arm of the same subjects. The main aim was to examine the effect of LV during a dumbbell biceps curl (Scott Curl) on isometric maximum force of the opposite muscle among the same subjects. It is hypothesized, that the intervention with LV produces a greater gain in isometric force of the arm flexors than ST. Twenty-seven collegiate students participated in the study. The training load was 70% of the individual 1 RM. Four sets with 12 repetitions were performed three times per week during four weeks. The right arm of all subjects represented the vibration trained body side (VS) and the left arm served as the traditional trained body side (TTS). A significant increase of isometric maximum force in both body sides (Arms) occurred. VS, however, significantly increased isometric maximum force about 43% in contrast to 22% of the TTS. The combined intervention of ST and LC improves isometric maximum force of arm flexor muscles. III.
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Erdoğan, Turan; Durakoğlugil, Murtaza Emre; Çiçek, Yüksel; Çetin, Mustafa; Duman, Hakan; Şatiroğlu, Ömer; Çelik, Şükrü
2017-03-01
Prolonged QRS duration is associated with decreased left ventricular (LV) systolic function. However, the relation between LV restrictive filling pattern (RFP) and QRS duration has not been investigated yet. The purpose of our study was to assess this relationship. We analyzed standard 12-lead surface electrocardiogram (ECG) of 155 consecutive patients. Mitral inflow and septal tissue velocities were obtained using the apical 4-chamber view with pulsed Doppler echocardiography. Patients were divided into 2 groups according to measured deceleration time (DT): restrictive (with DT ≤130 ms) or non-restrictive (with DT >130 ms). QRS duration was significantly longer in the restrictive group than in the non-restrictive group (0.101 vs. 0.090 s, p < 0.0001). QRS duration of >0.10 s was highly specific (82.6%), but modestly sensitive (64.7%), for the prediction of LV RFP. Multivariate analyses demonstrated that E/A ratio, peak E, peak A, septal e', and a' velocities were significantly associated with RFP. Prolonged QRS duration (>0.10 s) obtained from a standard resting 12-lead ECG is associated with LV RFP. However, the relationship of QRS duration with RFP was not independent of echocardiographic parameters.
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Ponschab, Martin; Schöchl, Herbert; Keibl, Claudia; Fischer, Henrik; Redl, Heinz; Schlimp, Christoph J
2015-10-06
Fluid resuscitation is a core stone of hemorrhagic shock therapy, and crystalloid fluids seem to be associated with lower mortality compared to colloids. However, as redistribution starts within minutes, it has been suggested to replace blood loss with a minimum of a three-fold amount of crystalloids. The hypothesis was that in comparison to high volume (HV), a lower crystalloid volume (LV) achieves a favorable coagulation profile and exerts sufficient haemodynamics in the acute phase of resuscitation. In 24 anaesthetized pigs, controlled arterial blood loss of 50 % of the estimated blood volume was either (n = 12) replaced with a LV (one-fold) or a HV (three-fold) volume of a balanced, acetated crystalloid solution at room temperature. Hemodynamic parameters, dilution effects and coagulation profile by standard coagulation tests and thromboelastometry at baseline and after resuscitation were determined in both groups. LV resuscitation increased MAP significantly less compared to the HV, 61 ± 7 vs. 82 ± 14 mmHg (p < 0.001) respectively, with no difference between lactate and base excess between groups. Haematocrit after fluid replacement was 0.20 vs. 0.16 (LV vs. HV, p < 0.001), suggesting a grade of blood dilution of 32 vs. 42 % (p < 0.001) compared to baseline values. Compared to LV, HV resulted in decreased core temperature (37.5 ± 0.2 vs. 36.0 ± 0.6 °C, p < 0.001), lower platelet count (318 ± 77 vs. 231 ± 53 K/μL, p < 0.01) and lower plasma fibrinogen levels (205 ± 19 vs. 168 ± 24 mg/dL, p < 0.001). Thromboelastometric measurements showed a significant impairment on viscoelastic clot properties following HV group. While prothrombin time index decreased significantly more in the HV group, activated partial thromboplastin time did not differ between both groups. HV did not result in hyperchloraemic acidosis. Coagulation parameters represented by plasma fibrinogen and ROTEM parameters were also less impaired with LV. With regrad to hematocrit, 60 % of LV remained intracascular , while in HV only 30 % remained in circulation within the first hour of administration. In the acute setting of 50 % controlled blood loss, a one fold LV crystalloid replacement strategy is sufficient to adequately raise blood pressure up to a mean arterial pressure >50 mm Hg. The concept of damage control resuscitation (DCR) with permissive hypotension may be better met by using LV as compared to a three fold HV resuscitation strategy. High volume administration of an acetated balanced crystalloid does not lead to hyperchloraemic acidosis, but may negatively influence clinical parameters, such as higher blood pressure, lower body temperature and impaired coagulation parameters, which could potentially increase bleeding after trauma. Replacement of acute blood loss with just an equal amount of an acetated balanced crystalloid appears to be the preferential treatment strategy in the acute phase after controlled bleeding.
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Dong, Yu; Zhang, Qingguo; Li, Yunxia; Jiang, Jia; Chen, Shiyi
2012-01-01
At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2) on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs) were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control), and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2) were used to reconstruct the anterior cruciate ligament (ACL) in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N) (P = 0.041 and P = 0.001, respectively). In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3) was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4) or control groups (12.4 ± 6.0) (p = 0.036 and 0.001, respectively). Based on the histological findings, there was an increased amount of perpendicular collagen fibers formed between the tendon and bone in the bMSCs+Lv-Control and bMSCs+Lv-BMP-2 group, compared with the gastrocnemius tendons. The proliferation of cartilage-like cells and the formation of fibrocartilage-like tissue were highest within the bone tunnels in the bMSCs+Lv-BMP-2 group. These results suggest that this lentivirus can be used to efficiently infect bMSCs with BMP-2. Furthermore, tendons wrapped by bMSCs+Lv-BMP-2 improved tendon–bone healing. PMID:23202970
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Yue, Bin; Lin, Yazhou; Ma, Xuexiao; Zhang, Guoqing; Chen, Bohua
2016-11-01
The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography‑guided puncture was performed at the L3‑L4 and L4‑L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration.
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Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency.
Tran, Reginald; Myers, David R; Denning, Gabriela; Shields, Jordan E; Lytle, Allison M; Alrowais, Hommood; Qiu, Yongzhi; Sakurai, Yumiko; Li, William C; Brand, Oliver; Le Doux, Joseph M; Spencer, H Trent; Doering, Christopher B; Lam, Wilbur A
2017-10-04
Ex vivo gene therapy using lentiviral vectors (LVs) is a proven approach to treat and potentially cure many hematologic disorders and malignancies but remains stymied by cumbersome, cost-prohibitive, and scale-limited production processes that cannot meet the demands of current clinical protocols for widespread clinical utilization. However, limitations in LV manufacture coupled with inefficient transduction protocols requiring significant excess amounts of vector currently limit widespread implementation. Herein, we describe a microfluidic, mass transport-based approach that overcomes the diffusion limitations of current transduction platforms to enhance LV gene transfer kinetics and efficiency. This novel ex vivo LV transduction platform is flexible in design, easy to use, scalable, and compatible with standard cell transduction reagents and LV preparations. Using hematopoietic cell lines, primary human T cells, primary hematopoietic stem and progenitor cells (HSPCs) of both murine (Sca-1 + ) and human (CD34 + ) origin, microfluidic transduction using clinically processed LVs occurs up to 5-fold faster and requires as little as one-twentieth of LV. As an in vivo validation of the microfluidic-based transduction technology, HSPC gene therapy was performed in hemophilia A mice using limiting amounts of LV. Compared to the standard static well-based transduction protocols, only animals transplanted with microfluidic-transduced cells displayed clotting levels restored to normal. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
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Gimelli, Alessia; Liga, Riccardo; Clemente, Alberto; Marras, Gavino; Kusch, Annette; Marzullo, Paolo
2017-01-12
Single-photon emission computed-tomography (SPECT) allows the quantification of LV eccentricity index (EI), a measure of cardiac remodeling. We sought to evaluate the feasibility of EI measurement with SPECT myocardial perfusion imaging and its interactions with relevant LV functional and structural parameters. Four-hundred and fifty-six patients underwent myocardial perfusion imaging on a Cadmium-Zinc-Telluride (CZT) camera. The summed rest, stress, and difference scores were calculated. From rest images, the LV end-diastolic (EDV) and end-systolic volumes, ejection fraction (EF), and peak filling rate (PFR) were calculated. In every patient, the EI, ranging from 0 (sphere) to 1 (line), was computed using a dedicated software (QGS/QPS; Cedars-Sinai Medical Center). Three-hundred and thirty-eight/456 (74%) patients showed a normal EF (>50%), while 26% had LV systolic dysfunction. The EI was computed from CZT images with excellent reproducibility (interclass correlation coefficient: 0.99, 95% CI 0.98-0.99). More impaired EI values correlated with the presence of a more abnormal LV perfusion (P < .001), function (EF and PFR, P < .001), and structure (EDV, P < .001). On multivariate analysis, higher EDV (P < .001) and depressed EF (P = .014) values were independent predictors of abnormal EI. The evaluation of LV eccentricity is feasible on gated CZT images. Abnormal EI associates with significant cardiac structural and functional abnormalities.
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Hovnanians, Ninel; Win, Theresa; Makkiya, Mohammed; Zheng, Qi; Taub, Cynthia
2017-11-01
To assess the efficiency and reproducibility of automated measurements of left ventricular (LV) volumes and LV ejection fraction (LVEF) in comparison to manually traced biplane Simpson's method. This is a single-center prospective study. Apical four- and two-chamber views were acquired in patients in sinus rhythm. Two operators independently measured LV volumes and LVEF using biplane Simpson's method. In addition, the image analysis software a2DQ on the Philips EPIQ system was applied to automatically assess the LV volumes and LVEF. Time spent on each analysis, using both methods, was documented. Concordance of echocardiographic measures was evaluated using intraclass correlation (ICC) and Bland-Altman analysis. Manual tracing and automated measurement of LV volumes and LVEF were performed in 184 patients with a mean age of 67.3 ± 17.3 years and BMI 28.0 ± 6.8 kg/m 2 . ICC and Bland-Altman analysis showed good agreements between manual and automated methods measuring LVEF, end-systolic, and end-diastolic volumes. The average analysis time was significantly less using the automated method than manual tracing (116 vs 217 seconds/patient, P < .0001). Automated measurement using the novel image analysis software a2DQ on the Philips EPIQ system produced accurate, efficient, and reproducible assessment of LV volumes and LVEF compared with manual measurement. © 2017, Wiley Periodicals, Inc.
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Fernandes, José Maria G; Rivera, Ivan Romero; de Oliveira Romão, Benício; Mendonça, Maria Alayde; Vasconcelos, Miriam Lira Castro; Carvalho, Antônio Carlos; Campos, Orlando; De Paola, Angelo Amato V; Moisés, Valdir A
2009-09-01
The Doppler-derived myocardial performance index (MPI) has been used in the evaluation of left ventricular (LV) function in several diseases. In patients with isolated diastolic dysfunction, the diagnostic utility of this index remains unclear. The aim of this study was to determine the diagnostic utility of MPI in patients with systemic hypertension, impaired LV relaxation, and normal ejection fraction. Thirty hypertensive patients with impaired LV relaxation were compared to 30 control subjects. MPI and its components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and the ejection time (ET), were measured from LV outflow and mitral inflow Doppler velocity profiles. MPI was higher in patients than in control subjects (0.45 +/- 0.13 vs 0.37 +/- 0.07 P < 0.0029). The increase in MPI was due to the prolongation of IRT without significant change of ICT and ET. MPI cutoff value of > or =0.40 identified impaired LV relaxation with a sensitivity of 63% and specificity of 70% while an IRT >94 ms had a sensitivity of 67% and specificity of 80%. Multivariate analysis identified relative wall thickness, mitral early filling wave velocity (E), and systolic myocardial velocity (Sm) as independent predictors of MPI in patients with hypertension. MPI was increase in patients with hypertension, diastolic dysfunction, and normal ejection fraction but was not superior to IRT to detect impaired LV relaxation.
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Bolin, Lisa L; Ahmad, Shamim; Lobelle-Rich, Patricia A; Ooms, Tara G; Alvarez-Hernandez, Xavier; Didier, Peter J; Levy, Laura S
2013-10-01
Feline leukemia virus (FeLV) is a naturally transmitted gammaretrovirus that infects domestic cats. FeLV-945, the predominant isolate associated with non-T-cell disease in a natural cohort, is a member of FeLV subgroup A but differs in sequence from the FeLV-A prototype, FeLV-A/61E, in the surface glycoprotein (SU) and long terminal repeat (LTR). Substitution of the FeLV-945 LTR into FeLV-A/61E resulted in pathogenesis indistinguishable from that of FeLV-A/61E, namely, thymic lymphoma of T-cell origin. In contrast, substitution of both FeLV-945 LTR and SU into FeLV-A/61E resulted in multicentric lymphoma of non-T-cell origin. These results implicated the FeLV-945 SU as a determinant of pathogenic spectrum. The present study was undertaken to test the hypothesis that FeLV-945 SU can act in the absence of other unique sequence elements of FeLV-945 to determine the disease spectrum. Substitution of FeLV-A/61E SU with that of FeLV-945 altered the clinical presentation and resulted in tumors that demonstrated expression of CD45R in the presence or absence of CD3. Despite the evident expression of CD45R, a typical B-cell marker, T-cell receptor beta (TCRβ) gene rearrangement indicated a T-cell origin. Tumor cells were detectable in bone marrow and blood at earlier times during the disease process, and the predominant SU genes from proviruses integrated in tumor DNA carried markers of genetic recombination. The findings demonstrate that FeLV-945 SU alters pathogenesis, although incompletely, in the absence of FeLV-945 LTR. Evidence demonstrates that FeLV-945 SU and LTR are required together to fully recapitulate the distinctive non-T-cell disease outcome seen in the natural cohort.
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Shalev, Zvi; Duffy, Simon P; Adema, Karen W; Prasad, Rati; Hussain, Naveen; Willett, Brian J; Tailor, Chetankumar S
2009-07-01
The pathogenic subgroup C feline leukemia virus (FeLV-C) arises in infected cats as a result of mutations in the envelope (Env) of the subgroup A FeLV (FeLV-A). To better understand emergence of FeLV-C and potential FeLV intermediates that may arise, we characterized FeLV Env sequences from the primary FY981 FeLV isolate previously derived from an anemic cat. Here, we report the characterization of the novel FY981 FeLV Env that is highly related to FeLV-A Env but whose variable region A (VRA) receptor recognition sequence partially resembles the VRA sequence from the prototypical FeLV-C/Sarma Env. Pseudotype viruses bearing FY981 Env were capable of infecting feline, human, and guinea pig cells, suggestive of a subgroup C phenotype, but also infected porcine ST-IOWA cells that are normally resistant to FeLV-C and to FeLV-A. Analysis of the host receptor used by FY981 suggests that FY981 can use both the FeLV-C receptor FLVCR1 and the feline FeLV-A receptor THTR1 for infection. However, our results suggest that FY981 infection of ST-IOWA cells is not mediated by the porcine homologue of FLVCR1 and THTR1 but by an alternative receptor, which we have now identified as the FLVCR1-related protein FLVCR2. Together, our results suggest that FY981 FeLV uses FLVCR1, FLVCR2, and THTR1 as receptors. Our findings suggest the possibility that pathogenic FeLV-C arises in FeLV-infected cats through intermediates that are multitropic in their receptor use.
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Usefulness of radionuclide angiocardiography in predicting stenotic mitral orifice area
DOE Office of Scientific and Technical Information (OSTI.GOV)
Burns, R.J.; Armitage, D.L.; Fountas, P.N.
1986-12-01
Fifteen patients with pure mitral stenosis (MS) underwent high-temporal-resolution radionuclide angiocardiography for calculation of the ratio of peak left ventricular (LV) filling rate divided by mean LV filling rate (filling ratio). Whereas LV filling normally occurs in 3 phases, in MS it is more uniform. Thus, in 13 patients the filling ratio was below the normal range of 2.21 to 2.88 (p less than 0.001). In 11 patients in atrial fibrillation, filling ratio divided by mean cardiac cycle length and by LV ejection fraction provided good correlation (r = 0.85) with modified Gorlin formula derived mitral area and excellent correlationmore » with echocardiographic mitral area (r = 0.95). Significant MS can be detected using radionuclide angiocardiography to calculate filling ratio. In the absence of the confounding influence of atrial systole calculation of 0.14 (filling ratio divided by cardiac cycle length divided by LV ejection fraction) + 0.40 cm2 enables accurate prediction of mitral area (+/- 4%). Our data support the contention that the modified Gorlin formula, based on steady-state hemodynamics, provides less certain estimates of mitral area for patients with MS and atrial fibrillation, in whom echocardiography and radionuclide angiocardiography may be more accurate.« less
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NASA Astrophysics Data System (ADS)
Wang, Yu; Wang, Yuxia; Chen, Lei; Wan, Qian-Hong
2012-02-01
Magnetic porous particles with dual functionality have been prepared by a two-step procedure and evaluated as novel restricted access materials for extraction of therapeutic agents from biological fluids. The magnetic silica particles served as scaffolds were first modified with diol groups, which were then converted to octadecyl esters through reaction with stearoyl chloride. In the second step, the octadecyl esters on the exterior surface were hydrolyzed by the action of lipase to yield magnetic particles with hydrophobic reversed-phase ligands on the inner surface and biocompatible diol groups on the outer surface. The restricted access behavior of the resulting materials was confirmed by differential binding of small molecules such as methotrexate (MTX), leucovorin (LV) and folic acid (FA) relative to bovine serum albumin. While MTX, LV and FA were all bound to the magnetic particles with high affinity, the adsorption of the protein was markedly reduced due to size exclusion effect. The utility of the magnetic particles for sample preparation was tested in solid-phase extraction of MTX, LV and FA from spiked human serum and the effects of the SPE conditions on the recovery of the analytes were systematically studied. Moreover, the magnetic particle-based sample preparation procedure coupled with reversed-phase liquid chromatography analysis was validated in terms of specificity, linearity and reproducibility. The method was shown to be free from interference of endogenous compounds and linear over the concentration range of 0.5-10 μg/mL for the three drugs studied. The limits of detection for the three drugs in serum were in the range of 0.160-0.302 μg/mL. Reproducibility expressed as the RSD of the recovery for ten replicated extractions at three different concentrations was found to be less than 8.93%. With a unique combination of surface functionality with magnetic cores, the restricted access magnetic particles may be adapted in automated and high throughput protocols for routine analysis of a large volume of clinical samples.
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Kim, Kyung-Hee; Kim, Yong-Jin; Ohn, Jung-Hun; Yang, Jimin; Lee, Sang-Eun; Lee, Sae-Won; Kim, Hyung-Kwan; Seo, Jeong-Wook; Sohn, Dae-Won
2012-03-20
We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic mitral regurgitation (MR). MR was created in Sprague-Dawley rats by making a hole on the mitral leaflet. Two weeks after MR creation, MR and LV dilatation were confirmed by echocardiography, and rats were randomly assigned to sildenafil treatment (MR+sildenafil group; 50 mg/kg PO twice a day; n=16) or normal saline only (MR group; n=16) and continued for 4 months. Sixteen sham rats were compared with MR rats. After 4 months, LV size was smaller in the MR+sildenafil compared with the MR group (LV end-systolic dimension, 4.7±0.3 for sham versus 5.9±0.3 for MR+sildenafil versus 7.4±0.5 mm for MR; P<0.05; LV end-diastolic dimension, 8.3±0.4 versus 10.5±0.2 versus 11.7±0.61 mm, respectively; P<0.05). LV ejection fraction was greater in the MR+sildenafil group than in the MR group (70.2±2.2 for sham versus 67.0±4.2 for MR+sildenafil versus 58.9±2.5 for MR; P=0.01). Serial treadmill test revealed that exercise capacity was reduced in the MR but not in the MR+sildenafil group. Transcriptional profiling of cardiac apical tissues revealed that gene sets related to inflammatory response, DNA damage response, cell cycle checkpoint, and cellular signaling pathways were significantly enriched by genes with reciprocal changes. Pathological analysis showed that perivascular fibrosis was more prominent in the MR than in the MR+sildenafil group and that the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells was 2-fold greater in the MR compared with the MR+sildenafil group. Sildenafil significantly attenuates LV remodeling and prevents exercise intolerance in a rat model of chronic MR. This benefit may be associated with the antiapoptotic, anti-inflammatory effects of sildenafil.
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Inoue, Yuko Y.; Ambale-Venkatesh, Bharath; Mewton, Nathan; Volpe, Gustavo J.; Ohyama, Yoshiaki; Sharma, Ravi K.; Wu, Colin O.; Liu, Chia-Ying; Bluemke, David A.; Soliman, Elsayed Z.; Lima, João A. C.
2017-01-01
Purpose To examine the associations of myocardial diffuse fibrosis and scar with surface electrocardiographic (ECG) parameters in individuals free of prior coronary heart disease in four different ethnicities. Materials and Methods This prospective cross-sectional study was approved by the institutional review boards, and all participants gave informed consent. A total of 1669 participants in the Multi-Ethnic Study of Atherosclerosis, or MESA, who were free of prior myocardial infarction underwent both ECG and cardiac magnetic resonance imaging. In individuals without a late gadolinium enhancement–defined myocardial scar (n = 1131), T1 mapping was used to assess left ventricular (LV) interstitial diffuse fibrosis. The associations of LV diffuse fibrosis or myocardial scar with ECG parameters (QRS voltage, QRS duration, and corrected QT interval [QTc]) were evaluated by using multivariable regression analyses adjusted for demographic data, risk factors for scar, LV end-diastolic volume, and LV mass. Results The mean age of the 1669 participants was 67.4 years ± 8.7 (standard deviation); 49.8% were women. Lower postcontrast T1 time at 12 minutes was significantly associated with lower QRS Sokolow-Lyon voltage (β = 15.1 µV/10 msec, P = .004), lower QRS Cornell voltage (β = 9.2 µV/10 msec, P = .031), and shorter QRS duration (β = 0.16 msec/10 msec, P = .049). Greater extracellular volume (ECV) fraction was also significantly associated with lower QRS Sokolow-Lyon voltage (β = −35.2 µV/1% ECV increase, P < .001) and Cornell voltage (β = −23.7 µV/1% ECV increase, P < .001), independent of LV structural indexes. In contrast, the presence of LV scar (n = 106) was associated with longer QTc (β = 4.3 msec, P = .031). Conclusion In older adults without prior coronary heart disease, underlying greater LV diffuse fibrosis is associated with lower QRS voltage and shorter QRS duration at surface ECG, whereas clinically unrecognized myocardial scar is associated with a longer QT interval. © RSNA, 2016 Online supplemental material is available for this article. PMID:27740904
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Xu, Jia-Ying; Liu, Dai; Zhong, Yang; Huang, Rong-Chong
2017-10-16
Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI). A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy. Thirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3-7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P < 0.00001) resulted in a significant increase of left ventricular ejection fraction (LVEF). As for the inhibitory effect on ventricular remodeling, BMC transplantation 3-7 days after PCI reduced LV end-diastolic indexes (-4.48; 95% CI, -7.98 to -0.98; P = 0.01) and LV end-systolic indexes (-6.73; 95% CI, -11.27 to -2.19; P = 0.004). However, in the groups who received BMC transplantation either within 24 hours or later than 7 days there was no significant effect on treatment outcome. In subgroup analysis, the group with LVEF ≤ 50% underwent a significant decrease in LV end-diastolic index after BMC transplantation (WMD = -3.29, 95% CI, -4.49 to -2.09; P < 0.00001); the decrease was even more remarkable in the LV end-systolic index after BMC transplantation in the group with LVEF ≤ 50% (WMD = -5.25, 95% CI, -9.30 to -1.20; P = 0.01), as well as in patients who received a dose of 10^7-10^8 cells (WMD = -12.99, 95% CI, -19.07 to -6.91; P < 0.0001). In the group with a follow-up of more than 12 months, this beneficial effect was significant and increased to a more pronounced effect of +3.58% (95% CI, 1.55 to 5.61; P = 0.0006) when compared with control. In this meta-analysis, BMC transfer at 3 to 7 days post-AMI was superior to transfer within 24 hours or more than 7 days after AMI in improving LVEF and decreasing LV end-systolic dimensions or LV end-diastolic dimensions. It is more effective in patients with lower baseline LVEF (≤50%) and the effect can last more than 12 months.
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Ahmed, Amany; Gondi, Sreedevi; Cox, Casey; Zheng, Minjuan; Mohammed, Anwarullah; Stupin, Igor V; Wang, Suwei; Vela, Deborah; Brewer, Alan; Elayda, Macarthur A; Buja, L Maximilian; Ward Casscells, S; Wilson, James M
2011-11-01
A declining amplitude of body temperature circadian rhythm (BTCR) predicts decompensation or death in cardiomyopathic hamsters. We tested the hypothesis that changes in BTCR amplitude accompany significant changes in left ventricular (LV) size and function. Using intraperitoneal transmitters, we continuously monitored the temperature of 30 male BIO TO-2 Syrian dilated cardiomyopathic hamsters. Cosinor analysis was used to detect significant changes--defined as changes >1 standard deviation from the baseline amplitude for 3 consecutive days--in BTCR amplitude over each hamster's lifespan. The Student t-test was used to compare BTCR variability and LV size and function (as assessed by 2D echocardiography) between baseline and the time that BTCR amplitude declined. All hamsters received 10 mg/kg furosemide daily. At the time of BTCR amplitude decline, functional parameters had changed significantly (P < .0001) from baseline: ejection fraction (0.31 ± 0.09% vs. 0.52 ± 0.08%), LV end-systolic volume (0.11 ± 0.03 vs. 0.05 ± 0.02 cm(3)), and LV end-diastolic volume (0.16 ± 0.04 vs. 0.10 ± 0.03 cm(3)). In decompensated cardiomyopathic hamsters, a decline in BTCR amplitude was associated with progression of heart failure and cardiac decompensation. Variation in BTCR warrants further investigation because of its potential implications for the diagnosis and treatment of cardiovascular disorders. Published by Elsevier Inc.
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Ahmet, Ismayil; Tae, Hyun-Jin; Lakatta, Edward G; Talan, Mark
2017-03-01
A short-term exposure to resveratrol at high dosages exerts a remarkable cardioprotective effect. Whether a long-term exposure to resveratrol at low dosages that can be obtained through consumption of a resveratrol-rich diet is beneficial to heart diseases is unknown. We tested the effects of a resveratrol-enriched diet on cardiovascular remodeling of chronic heart failure (CHF) in rats resulting from permanent ligation of left coronary artery. Two weeks after surgery, rats were started on either a resveratrol-enriched (R; 5 mg/kg per day; n = 23) or normal (Control; n = 23) diet for next 10 months. Serial echocardiography in Control showed a significant decline in LV ejection fraction, increases in LV end-systolic and end-diastolic volumes, and expansion in myocardial infarct from pre-treatment values. In R, compared with Control, there were substantial improvements in those parameters. End-point LV pressure-volume loop analysis showed a significantly improved LV systolic function and AV-coupling, an index of energy transfer efficacy between the heart and aortic tree, in R compared with Control (p < 0.05). Aortic pulse wave velocity, a measure of arterial stiffness, was significantly lower in R (389 ± 15 cm/s; p < 0.05) compared with Control (489 ± 38 cm/s). These results demonstrated that long-term dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in CHF.
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Platts, David G; Diab, Sara; Dunster, Kimble R; Shekar, Kiran; Burstow, Darryl J; Sim, Beatrice; Tunbridge, Matthew; McDonald, Charles; Chemonges, Saul; Chan, Jonathan; Fraser, John F
2015-03-01
Transthoracic echocardiography (TTE) during extra corporeal membrane oxygenation (ECMO) is important but can be technically challenging. Contrast-specific TTE can improve imaging in suboptimal studies. These contrast microspheres are hydrodynamically labile structures. This study assessed the feasibility of contrast echocardiography (CE) during venovenous (VV) ECMO in a validated ovine model. Twenty-four sheep were commenced on VV ECMO. Parasternal long-axis (Plax) and short-axis (Psax) views were obtained pre- and postcontrast while on VV ECMO. Endocardial definition scores (EDS) per segment were graded: 1 = good, 2 = suboptimal 3 = not seen. Endocardial border definition score index (EBDSI) was calculated for each view. Endocardial length (EL) in the Plax view for the left ventricle (LV) and right ventricle (RV) was measured. Summation EDS data for the LV and RV for unenhanced TTE (UE) versus CE TTE imaging: EDS 1 = 289 versus 346, EDS 2 = 38 versus 10, EDS 3 = 33 versus 4, respectively. Wilcoxon matched-pairs rank-sign tests showed a significant ranking difference (improvement) pre- and postcontrast for the LV (P < 0.0001), RV (P < 0.0001) and combined ventricular data (P < 0.0001). EBDSI for CE TTE was significantly lower than UE TTE for the LV (1.05 ± 0.17 vs. 1.22 ± 0.38, P = 0.0004) and RV (1.06 ± 0.22 vs. 1.42 ± 0.47, P = 0.0.0006) respectively. Visualized EL was significantly longer in CE versus UE for both the LV (58.6 ± 11.0 mm vs. 47.4 ± 11.7 mm, P < 0.0001) and the RV (52.3 ± 8.6 mm vs. 36.0 ± 13.1 mm, P < 0.0001), respectively. Despite exposure to destructive hydrodynamic forces, CE is a feasible technique in an ovine ECMO model. CE results in significantly improved EDS and increased EL. © 2014, Wiley Periodicals, Inc.
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Sengupta, Shantanu P; Jaju, Rahul; Nugurwar, Abhijeet; Caracciolo, Giuseppe; Sengupta, Partho P
2012-01-01
The status of left ventricle in sickle cell anemia presenting in sickle crisis and follow up has been minimally studied in past. To determine the left ventricular (LV) myocardial performance in these patients, we performed the study to assess two dimensional strains imaging which allowed a rapid and an accurate analysis of global and regional LV myocardial performance in longitudinal, radial, and circumferential directions. In this prospective study, 2-dimensional echocardiography (2DE) images of the LV were obtained in 52 subjects which included 32 patients (23 ± 8yrs, 16 male) with homozygous sickle cell anemia (SCA) in sickle cell crisis and 20 healthy controls (23 ± 5 yrs, 11 male) using apical 4-chamber and parasternal short-axis at the basal, mid, and apical levels. Of these 32 patients, 2DE was performed again in 18 patients in follow up (8 months ± 5 days). Longitudinal, circumferential and radial strains (LS, CS and RS respectively) were quantified and compared in an 18-segment model using a novel speckle tracking system (2D Cardiac Performance Analysis, TomTec Imaging System, Munich, Germany). There was no significant difference in LV ejection fraction between both the groups (59.32 ± 12.6 vs. 52.3 ± 7.9; p-value > 0.05). In comparison with normal controls and follow up of sickle cell patients, peak LS was significantly attenuated in the subendocardial and subepicardial regions during sickle cell crisis (p < 0.05). However, a significant reduction in circumferential strain was evident only in subepicardial region (p < 0.001). Also patients in sickle cell crisis showed significantly higher radial strain parameters than controls (p < 0.001). Patients with SCA presenting in sickle cell crisis have reduced longitudinal shortening. LV myocardial performance remains unaltered due to relatively preserved circumferential shortening and increased radial thickening. Copyright © 2012 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.
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Nebivolol prevents remodeling in a rat myocardial infarction model: an echocardiographic study.
Mercanoğlu, Güldem Olguner; Pamukçu, Burak; Safran, Nurhas; Mercanoğlu, Fehmi; Fici, Francesco; Güngör, Mehmet
2010-02-01
Ventricular remodeling (VR) which develops after myocardial infarction (MI) plays an important role in progressive left ventricular dysfunction. We aimed to investigate the role of nebivolol treatment on VR after a MI in a rat ischemia-reperfusion model. Rats were divided into 3 groups of 12 each: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). Left ventricular (LV) diameters, volumes, and diastolic filling parameters were evaluated by echocardiography. On the 28th day, after recording the systemic and LV pressures and determining the plasma nitric oxide (NO) and peroxynitrite (ONOO-) levels , animals were sacrificed and heart, body and LV weights (HW, BW, LVW) were measured and infarct sizes were determined. Results were evaluated statistically by ANOVA for repeated measurements 3x3 factorial design with post-hoc Bonferroni test. After MI, while VR (an increase in LV diameters and volumes associated with a decrease in EF, FS and posterior wall thickness change (LWPc) was significant in MI-control rats (p<0.05 for; all comparisons) these changes were significantly less in MI-nebivolol group (p=0.08 and p=0.06 for EF and FS respectively). LV end diastolic pressure (LVEDP) was lower (p<0.005) and Delta+/- dp/dt's (p<0.05) were higher in MI-nebivolol group compared to MI-control animals. Although infarct sizes were similar in MI-induced groups (p=0.79); LVW/HW and HW/BW's were significantly greater in the MI-control group compared to sham-control (p<0.01 for all comparisons), these changes were not statistically significant in MI-nebivolol group. The increase in plasma NO and ONOO- levels were also prevented with nebivolol. Nebivolol therapy reduced the effects of VR in rats after MI. These beneficial effects were not related to its heart rate and blood pressure reducing effects. Nitric oxide regulatory action of this compound may contribute these beneficial effects on VR developed after MI.
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Rodrigues, Jonathan C L; Rohan, Stephen; Ghosh Dastidar, Amardeep; Harries, Iwan; Lawton, Christopher B; Ratcliffe, Laura E; Burchell, Amy E; Hart, Emma C; Hamilton, Mark C K; Paton, Julian F R; Nightingale, Angus K; Manghat, Nathan E
2017-03-01
European guidelines state left ventricular (LV) end-diastolic wall thickness (EDWT) ≥15mm suggests hypertrophic cardiomyopathy (HCM), but distinguishing from hypertensive heart disease (HHD) is challenging. We identify cardiovascular magnetic resonance (CMR) predictors of HHD over HCM when EDWT ≥15mm. 2481 consecutive clinical CMRs between 2014 and 2015 were reviewed. 464 segments from 29 HCM subjects with EDWT ≥15mm but without other cardiac abnormality, hypertension or renal impairment were analyzed. 432 segments from 27 HHD subjects with EDWT ≥15mm but without concomitant cardiac pathology were analyzed. Magnitude and location of maximal EDWT, presence of late gadolinium enhancement (LGE), LV asymmetry (>1.5-fold opposing segment) and systolic anterior motion of the mitral valve (SAM) were measured. Multivariate logistic regression was performed. Significance was defined as p<0.05. HHD and HCM cohorts were age-/gender-matched. HHD had significantly increased indexed LV mass (110±27g/m 2 vs. 91±31g/m 2 , p=0.016) but no difference in site or magnitude of maximal EDWT. Mid-wall LGE was significantly more prevalent in HCM. Elevated indexed LVM, mid-wall LGE and absence of SAM were significant multivariate predictors of HHD, but LV asymmetry was not. Increased indexed LV mass, absence of mid-wall LGE and absence of SAM are better CMR discriminators of HHD from HCM than EDWT ≥15mm. • Hypertrophic cardiomyopathy (HCM) is often diagnosed with end-diastolic wall thickness ≥15mm. • Hypertensive heart disease (HHD) can be difficult to distinguish from HCM. • Retrospective case-control study showed that location and magnitude of EDWT are poor discriminators. • Increased left ventricular mass and midwall fibrosis are independent predictors of HHD. • Cardiovascular magnetic resonance parameters facilitate a better discrimination between HHD and HCM.
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Mapanao, Ratchaneegorn; Cheng, Winton
2016-09-01
Tyrosine hydroxylase (TH) belongs to the biopterin-dependent aromatic amino acid hydroxylase enzyme family, and it represents the first and rate-limiting step in the synthesis of catecholamines that are required for physiological and immune process in invertebrates and vertebrates. Cloned Litopenaeus vannamei TH (LvTH), containing a short alpha helix domain, a catalytic core, a regulatory domain, a phosphorylation site and two potential N-linked glycosylation sites as presented in vertebrate and insect THs without acidic region and signal peptide cleavage sites at the amino-terminal, exhibited a similarity of 60.0-61.2% and 45.0-47.0% to that of invertebrate and vertebrate THs, respectively. Further, LvTH expression was abundant in gill and haemocytes determined by quantitative real-time PCR. L. vannamei challenged with Vibrio alginolyticus at 10(5) cfu shrimp(-1) revealed significant increase of LvTH mRNA expression in haemocytes within 30-120 min and in brain within 15-30 min followed with recuperation. In addition, shrimps exposed to hypothermal stress at 18 °C significantly increased LvTH expression in haemocytes and brain within 30-60 and 15-60 min, respectively. The TH activity and haemolymph glucose level (haemocytes-free) significantly increased in pathogen challenged shrimp at 120 min and 60 min, and in hypothermal stressed shrimp at 30-60 and 30 min, respectively. These results affirm that stress response initiates in the brain while haemocytes display later response. Further, the significant elevation of TH activity in haemolymph is likely to confer by TH that released from haemocytes. In conclusion, the cloned LvTH in our current study is a neural TH enzyme appears to be involved in the physiological and immune responses of whiteleg shrimp, L. vannamei suffering stressful stimulation. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Siciliano, Mariachiara; Migliore, Federico; Badano, Luigi; Bertaglia, Emanuele; Pedrizzetti, Gianni; Cavedon, Stefano; Zorzi, Alessandro; Corrado, Domenico; Iliceto, Sabino; Muraru, Denisa
2017-11-01
To characterize the effect of multipoint pacing (MPP) compared to biventricular pacing (BiV) on left ventricle (LV) mechanics and intraventricular fluid dynamics by three-dimensional echocardiography (3DE) and echocardiographic particle imaging velocimetry (Echo-PIV). In 11 consecutive patients [8 men; median age 65 years (57-75)] receiving cardiac resynchronization therapy (CRT) with a quadripolar LV lead (Quartet,St.Jude Medical,Inc.), 3DE and Echo-PIV data were collected for each pacing configuration (CRT-OFF, BiV, and MPP) at follow-up after 6 months. 3DE data included LV volumes, LV ejection fraction (LVEF), strain, and systolic dyssynchrony index (SDI). Echo-PIV was used to evaluate the directional distribution of global blood flow momentum, ranging from zero, when flow force is predominantly along the base-apex direction, up to 90° when it becomes transversal. MPP resulted in significant reduction in end-diastolic and end-systolic volumes compared with both CRT-OFF (P = 0.02; P = 0.008, respectively) and BiV (P = 0.04; P = 0.03, respectively). LVEF and cardiac output were significant superior in MPP compared with CRT-OFF, but similar between MPP and BiV. Statistical significant differences when comparing global longitudinal and circumferential strain and SDI with MPP vs. CRT-OFF were observed (P = 0.008; P = 0.008; P = 0.01, respectively). There was also a trend towards improvement in strain between BiV and MPP that did not reach statistical significance. MPP reflected into a significant reduction of the deviation of global blood flow momentum compared with both CRT-OFF and BiV (P = 0.002) indicating a systematic increase of longitudinal alignment from the base-apex orientation of the haemodynamic forces. These preliminary results suggest that MPP resulted in significant improvement of LV mechanics and fluid dynamics compared with BiV. However, larger studies are needed to confirm this hypothesis. © Crown copyright 2016.
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Stroupe, Kevin T; Stelmack, Joan A; Tang, X Charlene; Wei, Yongliang; Sayers, Scott; Reda, Domenic J; Kwon, Ellen; Massof, Robert W
2018-05-01
Examining costs and consequences of different low-vision (LV) programs provides important information about resources needed to expand treatment options efficiently. To examine the costs and consequences of LV rehabilitation or basic LV services. The US Department of Veterans Affairs (VA) Low Vision Intervention Trial (LOVIT) II was conducted from September 27, 2010, to July 31, 2014, at 9 VA facilities and included 323 veterans with macular diseases and a best-corrected distance visual acuity of 20/50 to 20/200. Veterans were randomized to receive basic LV services that provided LV devices without therapy, or LV rehabilitation that added a therapist to LV services who provided instruction and homework on using LV devices, eccentric viewing, and environmental modification. We compared costs and consequences between these groups. Low-vision devices without therapy and LV devices with therapy. Costs of providing basic LV services or LV rehabilitation were assessed. We measured consequences as changes in functional visual ability from baseline to follow-up 4 months after randomization using the VA Low Vision Visual Functioning Questionnaire. Visual ability was measured in dimensionless log odds units (logits). Of 323 randomized patients, the mean (SD) age was 80 (10.5) years, 314 (97.2%) were men, and 292 (90.4%) were white. One hundred sixty (49.5%) received basic LV services and 163 (50.1%) received LV rehabilitation. The mean (SD) total direct health care costs per patient were similar between patients who were randomized to receive basic LV services ($1662 [$671]) or LV rehabilitation ($1788 [$864]) (basic LV services, $126 lower; 95% CI, $299 lower to $35 higher; P = .15). However, basic LV services required less time and had lower transportation costs. Patients receiving LV rehabilitation had greater improvements in overall visual ability, reading ability, visual information processing, and visual motor skill scores.
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Feng, Dong; Ge, Chun; Tan, Zhao-Yi; Sun, Jian-Guo; Xie, Yuan; Yao, Lan; Yan, Cai-Xia; Aa, Ji-Ye; Wang, Guang-Ji
2018-06-19
Xuezhikang capsule (XZK) is a traditional Chinese medicine that contains lovastatin (Lv) for hyperlipidemia treatment, although it has fewer side effects than Lv. However, the pharmacokinetic mechanisms contributing to its distinct efficacy and low side effects are unclear. Mice were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia. We first conducted the pharmacokinetic studies in HFD mice following oral administration of Lv (10 mg/kg, i.g.) and found that HFD remarkably decreased the active form of Lv (the lovastatin acid, LvA) exposure in the circulation system, especially in the targeting organ liver, with a declined conversion from Lv to LvA, whereas the Lv (responsible for myotoxicity) exposure in muscle markedly increased. Then we compared the pharmacokinetic profiles of Lv in HFD mice after the oral administration of XZK (1200 mg/kg, i.g.) or an equivalent dose of Lv (10 mg/kg, i.g.). A higher exposure of LvA and lower exposure of Lv were observed after XZK administration, suggesting a pharmacokinetic interaction of some ingredients in XZK. Further studies revealed that HFD promoted the inflammation and inhibited carboxylesterase (CES) activities in the intestine and the liver, thus contributing to the lower transformation of Lv into LvA. In contrast, XZK inhibited the inflammation and upregulated CES in the intestine and the liver. Finally, we evaluated the effects of monacolins and phytosterols, the fractional extracts of isoflavones, on inflammatory LS174T or HepG2 cells, which showed that isoflavones inhibited inflammation, upregulated CES, and markedly enhanced the conversion of Lv into LvA. For the first time, we provide evidence that isoflavones and Lv in XZK act in concert to enhance the efficacy and reduce the side effects of Lv.
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Birner, Christoph M; Ulucan, Coskun; Fredersdorf, Sabine; Rihm, Munhie; Löwel, Hannelore; Stritzke, Jan; Schunkert, Heribert; Hengstenberg, Christian; Holmer, Stephan; Riegger, Günter; Luchner, Andreas
2007-11-01
Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.
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Ghardashi Afousi, Alireza; Izadi, Mohammad Reza; Rakhshan, Kamran; Mafi, Farnoosh; Biglari, Soheil; Gandomkar Bagheri, Habibalah
2018-06-22
What is the central question of this study? Endothelial function is impaired because of increased oscillatory and retrograde shear in patients with type 2 diabetes. It is unclear whether low-volume high-intensity interval training and continuous moderate intensity exercise can modulate oscillatory and retrograde shear, blood flow and flow-mediated arterial dilation in these patients. What is the main finding and its importance? We found that low-volume high-intensity interval training, by increasing anterograde shear and decreasing retrograde shear and oscillatory index, can increase nitric oxide production and consequently result in increased flow-mediated dilation and outward arterial remodelling in patients with type 2 diabetes. Atherosclerosis in patients with type 2 diabetes is characterized by endothelial dysfunction associated with impaired flow-mediated dilation (FMD) and increases retrograde and oscillatory shear. The present study investigated endothelium-dependent vasodilation and shear rate in patients with type 2 diabetes at baseline and follow-up after 12 weeks of low-volume high-intensity interval training (LV-HIIT) or continuous moderate intensity training (CMIT). Seventy five sedentary patients with type 2 diabetes and untreated pre- or stage I hypertension were randomly divided into LV-HIIT, CMIT and control groups. The LV-HIIT group intervention was 12 intervals of 1.5 min at 85%-90% HR max and 2 min at 55%-60% HR max . The CMIT group intervention was 42 min of exercise at 70% HR max for 3 sessions per week during 12 weeks. High-resolution Doppler ultrasound was used to measure FMD, arterial diameter, anterograde and retrograde blood flow and shear rate patterns. Brachial artery FMD increased significantly in the LV-HIIT group (3.83 ± 1.13 baseline, 7.39 ± 3.6% follow-up), whereas there were no significant increase in the CMIT group (3.45 ± 0.97 baseline, 4.81 ± 2.36% follow-up) compared to the control group (3.16 ± 0.78 baseline, 4.04 ± 1.28% follow-up) (P < 0.05). Retrograde shear in the LV-HIIT group decreased significantly (P < 0.05), and no significant decrease in retrograde shear was seen in the CMIT group. Anterograde shear after LV-HIIT increased significantly (P < 0.05) but was unchanged in the CMIT group. However, oscillatory shear index in both exercise groups decreased significantly (P = 0.029). Nitrite/nitrate (NOx) level increased in both exercise groups, but the increase was greater in the LV-HIIT group (P < 0.001). Our results indicate that by increasing NOx, HIIT decreases the oscillatory shear-induced improvement in FMD and outward artery remodelling in patients with T2D. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Nesina, Stefanie; Katrin Helfer-Hungerbuehler, A; Riond, Barbara; Boretti, Felicitas S; Willi, Barbara; Meli, Marina L; Grest, Paula; Hofmann-Lehmann, Regina
2015-12-21
The feline leukemia virus (FeLV) is a gamma-retrovirus of domestic cats that was discovered half a century ago. Cats that are infected with FeLV may develop a progressive infection resulting in persistent viremia, immunodeficiency, tumors, anemia and death. A significant number of cats mount a protective immune response that suppresses viremia; these cats develop a regressive infection characterized by the absence of viral replication and the presence of low levels of proviral DNA. The biological importance of these latter provirus carriers is largely unknown. Here, we demonstrate that ten cats that received a transfusion of blood from aviremic provirus carriers developed active FeLV infections, some with a progressive outcome and the development of fatal FeLV-associated disease. The infection outcome, disease spectrum and evolution into FeLV-C in one cat mirrored those of natural infection. Two cats developed persistent antigenemia; six cats were transiently antigenemic. Reactivation of infection occurred in some cats. One recipient developed non-regenerative anemia associated with FeLV-C, and four others developed a T-cell lymphoma, one with secondary lymphoblastic leukemia. Five of the ten recipient cats received provirus-positive aviremic blood, whereas the other five received provirus- and viral RNA-positive but aviremic blood. Notably, the cats that received blood containing only proviral DNA exhibited a later onset but graver outcome of FeLV infection than the cats that were transfused with blood containing proviral DNA and viral RNA. Leukocyte counts and cytokine analyses indicated that the immune system of the latter cats reacted quicker and more efficiently. Our results underline the biological and epidemiological relevance of FeLV provirus carriers and the risk of inadvertent FeLV transmission via blood transfusion and demonstrate the replication capacity of proviral DNA if uncontrolled by the immune system. Our results have implications not only for veterinary medicine, such as the requirement for testing blood donors and blood products for FeLV provirus by sensitive polymerase chain reaction, but are also of general interest by revealing the importance of latent retroviral DNA in infected hosts. When aiming to eliminate a retroviral infection from a population, provirus carriers must be considered.
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Kırış, Abdulkadir; Kırış, Gülhanım; Karaman, Kayıhan; Sahin, Mürsel; Gedikli, Omer; Kaplan, Sahin; Orem, Asım; Kutlu, Merih; Kazaz, Zeynep
2012-10-01
Left ventricular (LV) dyssynchrony is a common finding in patients with hypertension and is associated with LV hypertrophy. Arterial stiffness (AS) and central (aortic) blood pressures play a significant role in end-organ damage such as LV hypertrophy caused by hypertension. The objective of this study was to investigate the relationship between AS, central blood pressures (BP) and LV dyssynchrony. Thirty-five newly diagnosed hypertensive patients and 40 controls were enrolled in the study. The entire study population underwent a comprehensive echocardiographic study including tissue synchrony imaging. The 12 segmental model was used to measure the time to regional peak systolic tissue velocity (Ts) in the LV and two dyssynchrony indices were computed. Parameters of AS including pulse wave velocity (PWV), augmentation index (AIx@75), and central systolic and diastolic BP were evaluated by applanation tonometry. The baseline clinical and echocardiographic parameters of both groups were similar except for their BPs. Dyssynchrony indices were prolonged in patients with hypertension as compared to the controls. The standart deviation of Ts of 12 LV segments in patients with hypertension and the controls were 48.7±18.8 vs. 25.8±13.1, respectively (p<0.001), and the maximal difference in Ts between any 2 of 12 LV segments was 143.9±52.2 for hypertension patients vs. 83.8±39.4 for controls (p<0.001). PWV (11.9±2.5 vs. 9.5±1.4, p<0.001), AIx@75 (27.4±8.3 vs. 18.3±9, p=0.009), and central systolic (147.6±20.8 vs. 105.4±11, p<0.001) and diastolic (99.8±14.4 vs. 72.8±9.5, p<0.001) pressures were higher in patients with hypertension than in the controls, respectively. In multivariable analysis, central systolic BP (ß=0.496, p=0.03), LV mass index (ß=0.232, p=0.027), and body mass index (ß=0.308, p=0.002) were found to be independently related to dyssynchrony. Central systolic BP is an independent predictor of LV dyssynchrony, but Aıx@75 did not have an independent effect on LV synchronicity in patients with newly-diagnosed hypertension.
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Zhang, Hai-Bo; Meng, Xu; Han, Jie; Li, Yan; Zhang, Ye; Jiang, Teng-Yong; Zhao, Ying-Xin; Zhou, Yu-Jie
2017-04-01
Transvenous lead placement is the standard approach for left ventricular (LV) pacing in cardiac resynchronization therapy (CRT), while the open chest access epicardial lead placement is currently the most frequently used second choice. Our study aimed to compare the ventricular electromechanical synchronicity in patients with heart failure after CRT with these two different LV pacing techniques. We enrolled 33 consecutive patients with refractory heart failure secondly to dilated cardiomyopathy who were eligible for CRT in this study. Nineteen patients received transvenous (TV group) while 14 received open chest (OP group) LV lead pacing. Intra- and inter-ventricular electromechanical synchronicity was assessed by tissue Doppler imaging (TDI) before and one year after CRT procedure. Before CRT procedure, the mean QRS-duration, maximum time difference to systolic peak velocity among 12 left ventricle segments (LV Ts-12), standard deviation of time difference to systolic peak velocity of 12 left ventricle segments (LV Ts-SD), and inter-ventricular mechanical delay (IVMD) in OP and TV group were 166 ± 17 ms and 170 ± 21 ms, 391 ± 42 ms and 397 ± 36 ms, 144 ± 30 ms and 148 ± 22 ms, 58 ± 25 ms and 60 ± 36 ms, respectively (all P > 0.05). At one year after the CRT, the mean QRS-duration, LV Ts-12, LV Ts-SD, and IVMD in TV and OP group were 128 ± 14 ms and 141 ± 22 ms ( P = 0.031), 136 ± 37 ms and 294 ± 119 ms ( P = 0.023), 50 ± 22 ms and 96 ± 34 ms ( P = 0.015), 27 ± 11 ms and 27 ± 26 ms ( P = 0.86), respectively. The LV lead implantation procedure time was 53.4 ± 16.3 min for OP group and 136 ± 35.1 min for TV group ( P = 0.016). The mean LV pacing threshold increased significantly from 1.7 ± 0.6 V/0.5 ms to 2.3 ± 1.6 V/0.5 ms ( P < 0.05) in TV group while it remained stable in the OP group. Compared to conventional endovascular approach, open chest access of LV pacing for CRT leads to better improvement of the intraventricular synchronization.
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Firstenberg, M S; Smedira, N G; Greenberg, N L; Prior, D L; McCarthy, P M; Garcia, M J; Thomas, J D
2001-09-18
Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular "suction." Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking. Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (tau), +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg; P<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=-0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=-1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85). Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.
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NASA Technical Reports Server (NTRS)
Firstenberg, M. S.; Smedira, N. G.; Greenberg, N. L.; Prior, D. L.; McCarthy, P. M.; Garcia, M. J.; Thomas, J. D.
2001-01-01
BACKGROUND: Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular "suction." Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking. METHODS AND RESULTS: Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (tau), +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg; P<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=-0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=-1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85). CONCLUSIONS: Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.
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Gallagher, Peter; Martin, Laura; Angel, Lori; Tomassoni, Gery
2007-02-01
The placement of left ventricular (LV) leads during cardiac resynchronization therapy (CRT) involves many technical difficulties. These difficulties increase procedural times and decrease procedural success rates. A total of 50 patients with severe cardiomyopathy (mean LV ejection fraction was 21 +/- 6%) and a wide QRS underwent CRT implantation. Magnetic navigation (Stereotaxis, Inc.) was used to position a magnet-tipped 0.014'' guidewire (Cronus guidewire) within the coronary sinus (CS) vasculature. LV leads were placed in a lateral CS branch, either using a standard CS delivery sheath or using a "bare-wire" approach without a CS delivery sheath. The mean total procedure time was 98.1 +/- 29.1 minutes with a mean fluoroscopy time of 22.7 +/- 15.1 minutes. The mean LV lead positioning time was 10.4 +/- 7.6 minutes. The use of a delivery sheath was associated with longer procedure times 98 +/- 32 minutes vs 80 +/- 18 minutes (P = 0.029), fluoroscopy times 23 +/- 15 minutes vs 13 +/- 4 minutes (P = 0.0007) and LV lead positioning times 10 +/- 6 minutes vs 4 +/- 2 minutes (P = 0.015) when compared to a "bare-wire" approach. When compared with 52 nonmagnetic-assisted control CRT cases, magnetic navigation reduced total LV lead positioning times (10.4 +/- 7.6 minutes vs 18.6 +/- 18.9 minutes; P = 0.005). If more than one CS branch vessel was tested, magnetic navigation was associated with significantly shorter times for LV lead placement (16.2 +/- 7.7 minutes vs 36.4 +/- 23.4 minutes; P = 0.004). Magnetic navigation is a safe, feasible, and efficient tool for lateral LV lead placement during CRT. Magnetic navigation during CRT allows for control of the tip direction of the Cronus 0.014'' guidewire using either a standard CS delivery sheath or "bare-wire" approach. Although there are some important limitations to the 0.014'' Cronus magnetic navigation can decrease LV lead placement times compared with nonmagnetic-assisted control CRT cases, particularly if multiple CS branches are to be tested.
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Effects of gene silencing of CypB on gastric cancer cells.
Guo, Feng; Zhang, Ying; Zhao, Chun-Na; Li, Lin; Guo, Yan-Jun
2015-04-01
To determine the effect of gene silencing of cyclophilin B (CypB) on growth and proliferation of gastric cancer cells. CypB siRNA lentivirus (LV-CypB-si) and control lentivirus (LV-si-con) were produced. CypB expression in gastric cancer cell lines was detected by Western blot. BGC823 and SGC7901 cells were chosen to be infected with LV-si-con and LV-CypB-si, and stable transfectants were isolated. The cell groups transfected with LV-CypB-siRNA, LV-siRNA-con and transfected no carrier were served as the experimental group, the implicit control group and the blank control group respectively. MTT and colony formation assays were used to examine the effect of CypB on the cell growth and proliferation in vitro. Cell cycle was analyzed with flow cytometry. The expression of VEGFR of BGC823-si and SGC7901-si was detected by Western blot. Gene silencing of CypB can inhibit gastric cancer cell growth, proliferation, cell cycle progress and tumorigenesis. CypB expression level was obviously higher in SGC7901 and BGC823 than MKN28 and GES. These two cell lines were infected with LV-si-con and LV-CypB-si respectively. MTT and cloney formation assays showed a significantly decreased rate of cell proliferation from the forth day or the fifth day in cells transfected with LV-CypB-si (P<0.05). Down-regulation of CypB resulted in slightly decreased percentage of S phase and increased percentage of G1 (P<0.05). These findings indicated that CypB could promote the G1-S transition of gastric cancer cell. In addition, the expression of VEGF of BGC823 and SGC7901 transfected with CypB siRNA was reduced in comparison with the implicit control group and the blank control group. Gene silencing of CypB decreases gastric cancer cells proliferation and in vivo tumorigenesis. These findings indiccate CypB could be a potential biomarker and therapeutic target for gastric cancer. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.
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Meli, Marina L.; Cattori, Valentino; Martínez, Fernando; López, Guillermo; Vargas, Astrid; Simón, Miguel A.; Zorrilla, Irene; Muñoz, Alvaro; Palomares, Francisco; López-Bao, Jose V.; Pastor, Josep; Tandon, Ravi; Willi, Barbara; Hofmann-Lehmann, Regina; Lutz, Hans
2009-01-01
Background The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. Methodology/ Principal Findings We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. Conclusions/Significance It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained. PMID:19270739
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Westman, Mark E; Paul, Amanda; Malik, Richard; McDonagh, Phillip; Ward, Michael P; Hall, Evelyn; Norris, Jacqueline M
2016-01-01
Our aim was to: (i) determine the current seroprevalence of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) in three large cohorts of cats from Australia; and (ii) investigate potential risk factors for retroviral infection. Cohort 1 (n = 2151 for FIV, n = 2241 for FeLV) consisted of cats surrendered to a shelter on the west coast of Australia (Perth, Western Australia [WA]). Cohort 2 (n = 2083 for FIV, n = 2032 for FeLV) consisted of client-owned cats with outdoor access recruited from around Australia through participating veterinary clinics. Cohort 3 (n = 169 for FIV, n = 166 for FeLV) consisted of cats presenting to Murdoch University Veterinary Hospital for a variety of reasons. Fresh whole blood was collected and tested using a commercially available point-of-care lateral flow ELISA kit that detects p27 FeLV antigen and antibodies to FIV antigens (p15 and p24) (cohorts 1 and 2), or one of two lateral flow immunochromatography kits that detect p27 antigen and antibodies to FIV antigen (p24 and/or gp40) (cohort 3). Data recorded for cats in cohort 2 included signalment, presenting complaint and postcode, allowing investigation of risk factors for FIV or FeLV infection, as well as potential geographical 'hot spots' for infection. The seroprevalence of FIV was 6% (cohort 1), 15% (cohort 2) and 14% (cohort 3), while the seroprevalence of FeLV was 1%, 2% and 4% in the same respective cohorts. Risk factors for FIV infection among cats in cohort 2 included age (>3 years), sex (male), neutering status (entire males) and location (WA had a significantly higher FIV seroprevalence compared with the Australian Capital Territory, New South Wales and Victoria). Risk factors for FeLV infection among cats in cohort 2 included health status ('sick') and location (WA cats were approximately three times more likely to be FeLV-infected compared with the rest of Australia). No geographical hot spots of FIV infection were identified. Both FIV and FeLV remain important infections among Australian cats. WA has a higher seroprevalence of both feline retroviruses compared with the rest of Australia, which has been noted in previous studies. A lower neutering rate for client-owned male cats is likely responsible for the higher seroprevalence of FIV infection in WA cats, while the reason for the higher seroprevalence of FeLV in WA cats is currently unknown.
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NASA Technical Reports Server (NTRS)
Nakatani, S.; Thomas, J. D.; Vandervoort, P. M.; Zhou, J.; Greenberg, N. L.; Savage, R. M.; McCarthy, P. M.
1997-01-01
OBJECTIVES: We studied the effects of left ventricular (LV) unloading by an implantable ventricular assist device on LV diastolic filling. BACKGROUND: Although many investigators have reported reliable systemic and peripheral circulatory support with implantable LV assist devices, little is known about their effect on cardiac performance. METHODS: Peak velocities of early diastolic filling, late diastolic filling, late to early filling ratio, deceleration time of early filling, diastolic filling period and atrial filling fraction were measured by intraoperative transesophageal Doppler echocardiography before and after insertion of an LV assist device in eight patients. A numerical model was developed to simulate this situation. RESULTS: Before device insertion, all patients showed either a restrictive or a monophasic transmitral flow pattern. After device insertion, transmitral flow showed rapid beat to beat variation in each patient, from abnormal relaxation to restrictive patterns. However, when the average values obtained from 10 consecutive beats were considered, overall filling was significantly normalized from baseline, with early filling velocity falling from 87 +/- 31 to 64 +/- 26 cm/s (p < 0.01) and late filling velocity rising from 8 +/- 11 to 32 +/- 23 cm/s (p < 0.05), resulting in an increase in the late to early filling ratio from 0.13 +/- 0.18 to 0.59 +/- 0.38 (p < 0.01) and a rise in the atrial filling fraction from 8 +/- 10% to 26 +/- 17% (p < 0.01). The deceleration time (from 112 +/- 40 to 160 +/- 44 ms, p < 0.05) and the filling period corrected by the RR interval (from 39 +/- 8% to 54 +/- 10%, p < 0.005) were also significantly prolonged. In the computer model, asynchronous LV assistance produced significant beat to beat variation in filling indexes, but overall a normalization of deceleration time as well as other variables. CONCLUSIONS: With LV assistance, transmitral flow showed rapidly varying patterns beat by beat in each patient, but overall diastolic filling tended to normalize with an increase of atrial contribution to the filling. Because of the variable nature of the transmitral flow pattern with the assist device, the timing of the device cycle must be considered when inferring diastolic function from transmitral flow pattern.
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Roth, D A; Urasawa, K; Helmer, G A; Hammond, H K
1993-01-01
The extent to which congestive heart failure (CHF) is dependent upon increased levels of the cardiac inhibitory GTP-binding protein (Gi), and the impact of CHF on the cardiac stimulatory GTP-binding protein (Gs) and mechanisms by which Gs may change remain unexplored. We have addressed these unsettled issues using pacing-induced CHF in pigs to examine physiological, biochemical, and molecular features of the right atrium (RA) and left ventricle (LV). CHF was associated with an 85 +/- 20% decrease in LV segment shortening (P < 0.001) and a 3.5-fold increase (P = 0.006) in the ED50 for isoproterenol-stimulated heart rate responsiveness. Myocardial beta-adrenergic receptor number was decreased 54% in RA (P = 0.004) and 57% in LV (P < 0.001), and multiple measures of adenylyl cyclase activity were depressed 49 +/- 8% in RA (P < 0.005), and 44 +/- 9% in LV (P < 0.001). Quantitative immunoblotting established that Gi and Gs were decreased in RA (Gi: 59% reduction; P < 0.0001; Gs: 28% reduction; P < 0.007) and LV (Gi: 35% reduction; P < 0.008; Gs: 28% reduction; P < 0.01) after onset of CHF. Reduced levels of Gi and Gs were confirmed by ADP ribosylation studies, and diminished function of Gs was established in reconstitution studies. Steady state levels for Gs alpha mRNA were increased in RA and unchanged in LV, and significantly more GS alpha was found in the supernatant (presumably cytosolic) fraction in RA and LV membrane homogenates after CHF, suggesting that increased Gs degradation, rather than decreased Gs synthesis, is the mechanism by which Gs is downregulated. We conclude that cardiac Gi content poorly predicts adrenergic responsiveness or contractile function, that decreased Gs is caused by increased degradation rather than decreased synthesis, and that alterations in beta-adrenergic receptors, adenylyl cyclase, and GTP-binding proteins are uniform in RA and LV in this model of congestive heart failure. Images PMID:8383705
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Yoon, Ji Hyun; Son, Jung Woo; Chung, Hyemoon; Park, Chul Hwan; Kim, Young-Jin; Chang, Hyuk-Jae; Hong, Geu-Ru; Kim, Tae Hoon; Ha, Jong-Won; Choi, Byoung Wook; Rim, Se-Joong; Chung, Namsik; Choi, Eui-Young
2015-01-01
Post-contrast T1 values are closely related to the degree of myocardial extracellular space expansion. We determined the relationship between post-contrast T1 values and left ventricular (LV) diastolic function, LV remodeling, and neurohormonal activation in patients with dilated cardiomyopathy (DCM). Fifty-nine patients with DCM (mean age, 55 ± 15 years; 41 males and 18 females) who underwent both 1.5T magnetic resonance imaging and echocardiography were enrolled. The post-contrast 10-minute T1 value was generated from inversion time scout images obtained using the Look-Locker inversion recovery sequence and a curve-fitting algorithm. The T1 sample volume was obtained from three interventricular septal points, and the mean T1 value was used for analysis. The N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level was measured in 40 patients. The mean LV ejection fraction was 24 ± 9% and the post-T1 value was 254.5 ± 46.4 ms. The post-contrast T1 value was significantly correlated with systolic longitudinal septal velocity (s'), peak late diastolic velocity of the mitral annulus (a'), the diastolic elastance index (Ed, [E/e']/stroke volume), LV mass/volume ratio, LV end-diastolic wall stress, and LV end-systolic wall stress. In a multivariate analysis without NT-proBNP, T1 values were independently correlated with Ed (β = -0.351, p = 0.016) and the LV mass/volume ratio (β = 0.495, p = 0.001). When NT-proBNP was used in the analysis, NT-proBNP was independently correlated with the T1 values (β = -0.339, p = 0.017). Post-contrast T1 is closely related to LV remodeling, diastolic function, and neurohormonal activation in patients with DCM.
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Sukhumavasi, Woraporn; Bellosa, Mary L; Lucio-Forster, Araceli; Liotta, Janice L; Lee, Alice C Y; Pornmingmas, Pitcha; Chungpivat, Sudchit; Mohammed, Hussni O; Lorentzen, Leif; Dubey, J P; Bowman, Dwight D
2012-08-13
The seroprevalence of Toxoplasma gondii, Dirofilaria immitis (heartworm), feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) infections was examined using serum or plasma samples from 746 pet cats collected between May and July 2009 from clinics and hospitals located in and around Bangkok, Thailand. The samples were tested for heartworm, FIV, and FeLV using a commercial ELISA. Of the 746 samples, 4.6% (34/746) were positive for heartworm antigen, 24.5% (183/746) had circulating FeLV antigen, and 20.1% (150/746) had antibodies against FIV. In addition, the first 348 submitted samples were tested for T. gondii antibodies using a modified agglutination test (MAT, cut off 1:25); 10.1% (35/348) were seropositive. Of the 348 cats sampled for all four pathogens, 11, 10, and 1 were positive for T. gondii antibodies and FIV antibodies, FeLV antigen, or D. immitis antigen, respectively. Of the 35 T. gondii-seropositive cats, 42.9% (15/35) were co-infected with at least one of the other three pathogens. The presence of antibodies to FIV was significantly associated with both age and gender, while FeLV antigen presence was only associated with age. In the case of FIV, males were twice as likely to be infected as females, and cats over 10 years of age were 13.5 times more likely to be infected than cats less than 1 year of age. FeLV antigen was more common in younger cats, with cats over 10 years of age being 10 times less likely to be FeLV positive than cats under 1 year of age. This is the first survey for these four pathogens affecting feline health in Thailand. Copyright © 2012 Elsevier B.V. All rights reserved.
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Souron, Robin; Besson, Thibault; McNeil, Chris J.; Lapole, Thomas; Millet, Guillaume Y.
2017-01-01
Local vibration (LV) has been recently validated as an efficient training method to improve muscle strength. Understanding the acute effects may help elucidate the mechanism(s). This study aimed to investigate the effects of a single bout of prolonged LV on knee extensor force production and corticospinal responsiveness of vastus lateralis (VL) and rectus femoris (RF) muscles in healthy young and old adults. Across two visits, 23 adult subjects (20–75 years old) performed pre- and post-test measurements, separated by 30-min of either rest (control; CON) or LV. Maximal voluntary contraction (MVC) force was assessed and transcranial magnetic stimulation (TMS) was used to evaluate cortical voluntary activation (VATMS) as well as the motor evoked potential (MEP) and silent period (SP). In 11 young adults, thoracic electrical stimulation was used to assess the thoracic motor evoked potential (TMEP). Although MVC decreased after both CON (−6.3 ± 4.4%, p = 0.01) and LV (−12.9 ± 7.7%, p < 0.001), the MVC loss was greater after LV (p = 0.001). Normalized maximal electromyographic (EMG) activity decreased after LV for both VL (−25.1 ± 10.7%) and RF (−20.9 ± 16.5%; p < 0.001), while it was unchanged after CON (p = 0.32). For RF, the TMEP and MEP/TMEP ratio decreased (p = 0.01) and increased (p = 0.01) after LV, respectively. Both measures were unchanged for VL (p = 0.27 and p = 0.15, respectively). No changes were reported for TMS-related parameters. These results confirm our hypothesis that modulations within the central nervous system would accompany the significant reduction of maximal voluntary force. A reduced motoneuron excitability seems to explain the decreased MVC after prolonged LV, as suggested by reductions in maximal EMG (all subjects) and TMEP area (data from 11 young subjects). A concomitant increased cortical excitability seems to compensate for lower excitability at the spinal level. PMID:29118698
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Litwin, Sheldon E; Katz, Sarah E; Morgan, James P; Douglas, Pamela S
1999-01-01
Chronic treatment with beta-adrenergic blocking agents can improve survival in patients with heart failure. The mechanisms underlying the beneficial effects and whether these effects are generalizable to ischaemic heart failure are unresolved.We performed echocardiographic-Doppler examinations in rats (n=28) 1 and 6 weeks after myocardial infarction (MI) or sham surgery. Rats were randomized to no treatment or propranolol (500 mg/l in drinking water) after the first echocardiogram. Isometric contractions and intracellular Ca transients were recorded simultaneously in noninfarcted left ventricular (LV) papillary muscles.Untreated MI rats had significant LV dilatation (10.6±0.4* vs 8.9±0.3 mm, MI vs control), impaired systolic function (fractional shortening=11±2* vs 38±2%), and a restrictive LV diastolic filling pattern. MI rats receiving propranolol had similar LV chamber sizes (10.6±0.5 mm) and systolic function (13±2%). The propranolol treated animals had higher LV end-diastolic pressures (27±2* vs 20±3 mmHg) and a more restricted LV diastolic filling pattern (increased ratio of early to late filling velocities and more rapid E wave deceleration rate). Contractility of papillary muscles from untreated MI rats was depressed (1.6±0.3 vs 2.4±0.5 g mm−2). In addition, Ca transients were prolonged and the inotropic response to isoproterenol was blunted. Propranolol treatment did not improve force development (1.6±0.3 g mm−2) or the duration of Ca transients during isoproterenol stimulation.Chronic propranolol treatment in rats with postinfarction heart failure did not improve LV remodeling or systolic function. LV diastolic pressures and filling patterns were worsened by propranolol. Treatment also did not produce appreciable improvement in contractility, intracellular Ca regulation or beta-adrenergic responsiveness in the noninfarcted myocardium. PMID:10455325
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Tsao, Connie W; Gona, Philimon N; Salton, Carol J; Chuang, Michael L; Levy, Daniel; Manning, Warren J; O'Donnell, Christopher J
2015-09-15
Elevated left ventricular mass index (LVMI) and concentric left ventricular (LV) remodeling are related to adverse cardiovascular disease (CVD) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized. Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65±9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002-2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person-years of follow-up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable-adjusted proportional hazards regression models, each 10-g/m(2) increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD, respectively (P=0.004 and P=0.009, respectively). The association between LV mass/LV end-diastolic volume and incident CVD was borderline significant (P=0.053). Multivariable-adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C-statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness). Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
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Desai, Milind Y; Gupta, Sandeep; Bomma, Chandra; Tandri, Harikrishna; Foo, Thomas K; Lima, Joao A C; Bluemke, David A
2005-01-01
Delayed post-contrast magnetic resonance (MR) imaging involves suppression of signal from myocardium using inversion times (TI) between 150-225 ms, when the myocardium appears dark and fibrotic scar appears bright. We noticed that at a TI optimized for signal suppression of the left ventricle (LV), the right ventricle (RV) appeared brighter. The purpose of this study was to evaluate the TI for signal suppression in RV compared to LV, and to try and identify the cause of this observation. Methods. We studied 31 patients (ages ranged from 17-79 years, 11 females) who had an MR scan on a 1.5 T GE scanner. Delayed post-contrast short-axis images were obtained 20 minutes after injection of 0.2 mmol/kg of intravenous gadolinium chelate. TI optimization was performed by acquiring a range of TI times within a single breath hold, in increments of 25 msec. The TI time that resulted in lowest signal for the RV arid LV was recorded. With the imaging sequence employed, the TI leading to LV signal suppression ranged from 150-225 ms. At the TI that resulted in LV signal suppression, the corrected signal from the RV was significantly higher as compared to the LV (29 +/- 13 au vs. 15 +/- 8 au, p < 0.001). The findings were similar using only the body coil. The TI required to suppress the RV was usually < or =150 msec. The observation persisted before and after gadolinium infusion. The TI for myocardial signal suppression appears to be different between LV and RV. Potential mechanisms include partial volume averaging with fat or blood pool (related to increased trabeculation) in the RV. Alternatively, increased blood pool signal (within Thebesian veins or arterioluminal communications) in RV compared to LV leads to altered TI times due to similar partial volume effects.
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Eerola, Anneli; Jokinen, Eero; Boldt, Talvikki; Pihkala, Jaana
2006-03-07
We aimed to evaluate the effect of percutaneous closure of patent ductus arteriosus (PDA) on left ventricular (LV) hemodynamics. Today, most PDAs are closed percutaneously. Little is known, however, about hemodynamic changes after the procedure. Of 37 children (ages 0.6 to 10.6 years) taken to the catheterization laboratory for percutaneous PDA closure, the PDA was closed in 33. Left ventricular diastolic and systolic dimensions, volumes, and function were examined by two-dimensional (2D) and three-dimensional (3D) echocardiography and serum concentrations of natriuretic peptides measured before PDA closure, on the following day, and 6 months thereafter. Control subjects comprised 36 healthy children of comparable ages. At baseline, LV diastolic diameter measured >+2 SD in 5 of 33 patients. In 3D echocardiography, a median LV diastolic volume measured 54.0 ml/m2 in the control subjects and 58.4 ml/m2 (p < 0.05) in the PDA group before closure and 57.2 ml/m2 (p = NS) 6 months after closure. A median N-terminal brain natriuretic peptide (pro-BNP) concentration measured 72 ng/l in the control group and 141 ng/l in the PDA group before closure (p = 0.001) and 78.5 ng/l (p = NS) 6 months after closure. Patients differed from control subjects in indices of LV systolic and diastolic function at baseline. By the end of follow-up, all these differences had disappeared. Even in the subgroup of patients with normal-sized LV at baseline, the LV diastolic volume decreased significantly during follow-up. Changes in LV volume and function caused by PDA disappear by 6 months after percutaneous closure. Even the children with normal-sized LV benefit from the procedure.
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Chen, Chi; Sung, Kuo-Tzu; Shih, Shou-Chuan; Liu, Chuan-Chuan; Kuo, Jen-Yuan; Hou, Charles Jia-Yin; Hung, Chung-Lieh; Yeh, Hung-I
2016-01-01
Advanced age is associated with left ventricle (LV) remodeling and impaired cardiac function that may increase the risk of heart failure. Even so, studies regarding age-related cardiac remodeling in a large, asymptomatic Asian population remain limited. We studied 8,410 asymptomatic participants (49.7 ±11.7 y, 38.9% women) in a health evaluation cohort (2004-2012) at a tertiary center in Northern Taiwan. We analyzed age-related alterations for all echocardiography-derived cardiac structures/functions and the associations with circulating N-terminal prohormone of brain natriuretic peptide (NT-proBNP). We also explored sex-related differences in these measures. In our cohort of 8,410 participants, advanced age was associated with greater LV wall thickness, larger LV total mass (+5.08 g/decade), and greater LV mass index (4.41 g/m2/decade), as well as increased serum NT-proBNP level (+18.89 pg/mL/decade). An accompanying reduction of stress-corrected midwall fractional shortening (-0.1%/decade) with aging was apparent in women after multi-variate adjustment (-0.09%/decade, p = 0.001). Furthermore, women demonstrated greater overall increase in LV wall thickness, LV mass index, and NT-proBNP compared to men (p for interaction: <0.001). All blood pressure components, including systolic, diastolic, and pulse pressures were independently associated with greater wall thickness and LV mass index after adjustment for confounders (all p <0.001). The associations between age and cardiac remodeling or mid-wall functions were further confirmed in a subset of study subjects with repeated follow up by GEE model. Significant associations of unfavorable LV remodeling and advanced age in our asymptomatic Asian population were observed, along with sex differences. These data may help explain the incidence of some diverse gender-related cardiovascular diseases, especially heart failure.
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Molecular cytogenetic analysis of feline leukemia virus insertions in cat lymphoid tumor cells.
Fujino, Yasuhito; Satoh, Hitoshi; Ohno, Koichi; Tsujimoto, Hajime
2010-02-01
This study was conducted to map the acquired proviral insertions in the chromosomal genome of feline lymphoid tumors induced by feline leukemia virus (FeLV). Chromosome specimens of the lymphoid tumor-derived cell lines and normal cat lymphocytes were subjected to fluorescence in situ hybridization and tyramide signal amplification, using an exogenous FeLV-A genome as a probe. Specific hybridization signals were detected only on the metaphase chromosomes of the tumor cells. Poisson's distribution-based statistics indicated that 6 chromosomal loci in each cell line showed FeLV integration. In the examination of metaphase chromosomes of FL-74, FT-1 and KO-1 cells, significant signals were detected on B2p15-p14, B2q11, D1p14, E1p14-p13, E1q12 and F2q16; A2p23-p22, B2p15-p14, B4p15-p14, D4q23-q24, E1p14-p13 and E2p13-p12; and A2p22, A3q22, B1p13, B1q13, D1p13 and D3p15-p14, respectively. Consistently, Southern blot hybridization using an FeLV LTR-U3 probe specific for exogenous FeLV revealed the presence of at least 6 copies of exogenous FeLV proviruses at different integration sites in each cell line. These results indicate that there may be common FeLV integration sites at least in A2p22 and B2p15-p14. The cytogenetic analysis used in this study can promptly screen FeLV insertions and provide tags for identifying the novel common integration site. 2009 Elsevier B.V. All rights reserved.
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Choi, Jin-Oh; Daly, Richard C; Lin, Grace; Lahr, Brian D; Wiste, Heather J; Beaver, Thomas M; Iacovoni, Attilio; Malinowski, Marcin; Friedrich, Ivar; Rouleau, Jean L; Favaloro, Roberto R; Sopko, George; Lang, Irene M; White, Harvey D; Milano, Carmelo A; Jones, Robert H; Lee, Kerry L; Velazquez, Eric J; Oh, Jae K
2015-04-01
We sought to evaluate associations between baseline sphericity index (SI) and clinical outcome, and changes in SI after coronary artery bypass graft (CABG) surgery with or without surgical ventricular reconstruction (SVR) in ischaemic cardiomyopathy patients enrolled in the SVR study (Hypothesis 2) of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Among 1000 patients in the STICH SVR study, we evaluated 546 patients (255 randomized to CABG alone and 291 to CABG + SVR) whose baseline SI values were available. SI was not significantly different between treatment groups at baseline. After 4 months, SI had increased in the CABG + SVR group, but was unchanged in the CABG alone group (0.69 ± 0.10 to 0.77 ± 0.12 vs. 0.67 ± 0.07 to 0.66 ± 0.09, respectively; P < 0.001). SI did not significantly change from 4 months to 2 years in either group. Although LV end-systolic volume and EF improved significantly more in the CABG + SVR group compared with CABG alone, the severity of mitral regurgitation significantly improved only in the CABG alone group, and the estimated LV filling pressure (E/A ratio) increased only in the CABG + SVR group. Higher baseline SI was associated with worse survival after surgery (hazard ratio 1.21, 95% confidence interval 1.02 - 1.43; P = 0.026). Survival was not significantly different by treatment strategy. Although SVR was designed to improve LV geometry, SI worsened after SVR despite improved LVEF and smaller LV volume. Survival was significantly better in patients with lower SI regardless of treatment strategy. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.
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Aktoz, Meryem; Yilmaztepe, Mustafa; Tatli, Ersan; Turan, Fatma Nesrin; Umit, Elif G; Altun, Armagan
2011-01-01
The aim of this study was to investigate ventricular functions and left atrial (LA) mechanical functions, atrial electromechanical coupling, and P wave dispersion in scleroderma patients. Twenty-six patients with scleroderma and twenty-four controls were included. Left and right ventricular (LV and RV) functions were evaluated using conventional echocardiography and tissue Doppler imaging (TDI). LA volumes were measured using the biplane area- -length method and LA mechanical function parameters were calculated. Inter-intraatrial electromechanical delays were measured by TDI. P wave dispersion was calculated by 12-lead electrocardiograms. LV myocardial performance indices (MPI) and RV MPI were higher in patients with scleroderma (p = 0.000, p = 0.000, respectively) while LA passive emptying fraction was decreased and LA active emptying fraction was increased (p = 0.051, p = 0.000, respectively). P wave dispersion and inter-intraatrial electromechanical delay were significantly higher in patients with scleroderma (25 [10-60] vs 20 [0-30], p = 0.000, 16.50 [7.28-26.38] vs 9.44 [3.79-15.78] and 11.33 [4.88-16.06] vs 4.00 [0-12.90], p < 0.05, respectively). Interatrial electromechanical delay was negatively correlated with LV E wave, (p = 0.018). LV E wave was demonstrated to be a factor independent of the interatrial electromechanical delay (R² = = 0.270, b = -0.52, p = 0.013). This study showed that in scleroderma patients, global functions of LV, RV and mechanical functions of LA were impaired, intra-interatrial electromechanical delays were prolonged and P wave dispersion was higher. LV E wave was demonstrated to be a factor that is independent of the interatrial electromechanical delay. Reduced LV E wave may also give additional information on the process of risk stratification of atrial fibrillation.
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Cai, Yi-Ming; Chen, Ting; Ren, Chun-Hua; Huang, Wen; Jiang, Xiao; Gao, Yan; Huo, Da; Hu, Chao-Qun
2017-05-01
The sodium bicarbonate cotransporter (NBC) is an integral membrane ion transporter that can transport HCO 3 - (or a related species, such as CO 3 2- ) across the plasma membrane. Previous researches revealed that NBC might play an important role in the regulation of intracellular pH in vertebrates. In the present study, an NBC cDNA was identified from Pacific white shrimp (Litopenaeus vannamei) and designated as Lv-NBC. The full-length Lv-NBC cDNA is 4479 bp in size, containing a 5'-untranslated region (UTR) of 59 bp, a 3'-UTR of 835 bp and an open reading frame (ORF) of 3585 bp that encodes a protein of 1194 amino acids with a deduced molecular weight of 134.34 kDa. The Lv-NBC protein contains two functional domains (Band_3_cyto and HCO3_cotransp) and twelve transmembrane (TM) domains. Expression of the Lv-NBC mRNA was ubiquitously detected in all selected tissues, with the highest level in the gill. By in situ hybridization (ISH) with Digoxigenin-labeled probe, the Lv-NBC positive cells were shown mainly located in the secondary gill filaments. After low or high pH challenge, the transcript levels of Lv-NBC in the gill were found to be up-regulated. After knockdown of the Lv-NBC level by siRNA, the mortality of shrimp significantly increased under pH stress. Our study, as a whole, may provide evidences for the role of NBC in shrimp responding to pH stress, and give a new insight of the acid/base homeostasis mechanism in crustaceans. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Villarreal, C; Rodriguez, M H; Bown, D N; Arredondo-Jiménez, J I
1995-04-01
Village-scale trials were carried out in southern Mexico to compare the efficacy of indoor-spraying of the pyrethroid insecticide lambda-cyhalothrin applied either as low-volume (LV) aqueous emulsion or as wettable-powder (WP) aqueous suspension for residual control of the principal coastal malaria vector Anopheles albimanus. Three indoor spray rounds were conducted at 3-month intervals using back-pack mist-blowers to apply lambda-cyhalothrin 12.5 mg a.i./m2 by LV, whereas the WP was applied by conventional compression sprayer at a mean rate of 26.5 mg a.i./m2. Both treatments caused mosquito mortality indoors and outdoors (collected inside house curtains) as a result of contact with treated surfaces before and after feeding, but had no significant impact on overall population density of An. albimanus resting indoors or assessed by human bait collections. Contact bioassays showed that WP and LV treatments with lambda-cyhalothrin were effective for 12-20 weeks (> 75% mortality) without causing excito-repellency. Compared to the WP treatment (8 houses/man/day), LV treatment (25 houses/man/day) was more than 3 times quicker per house, potentially saving 68% of labour costs. This is offset, however, by the much lower unit price of a compression sprayer (e.g. Hudson 'X-pert' at US$120) than a mist-blower (e.g. 'Super Jolly' at US$350), and higher running costs for LV applications. It was calculated, therefore, that LV becomes more economical than WP after 18.8 treatments/100 houses/10 men at equivalent rates of application, or after 7.6 spray rounds with half-rate LV applications.
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Levy, J K; Crawford, P Cynda; Tucker, S J
2017-03-01
More than 3 million cats in the United States are infected with FeLV or FIV. The cornerstone of control is identification and segregation of infected cats. To compare test performance with well-characterized clinical samples of currently available FeLV antigen/FIV antibody combination test kits. Surplus serum and plasma from diagnostic samples submitted by animal shelters, diagnostic laboratories, veterinary clinics, and cat research colonies. None of the cats had been vaccinated against FIV. The final sample set included 146 FeLV+, 154 FeLV-, 94 FIV+, and 97 FIV- samples. Prospective, blind comparison to a gold standard: Samples were evaluated in 4 different point-of-care tests by ELISA antigen plate tests (FeLV) and virus isolation (FIV) as the reference standards. All test results were visually read by 2 blinded observers. Sensitivity and specificity, respectively, for FeLV were SNAP ® (100%/100%), WITNESS ® (89.0%/95.5%), Anigen ® (91.8%/95.5%), and VetScan ® (85.6%/85.7%). Sensitivity and specificity for FIV were SNAP ® (97.9%/99.0%), WITNESS ® (94.7%/100%), Anigen ® (96.8%/99.0%), and VetScan ® (91.5%/99.0%). The SNAP ® test had the best performance for FeLV, but there were no significant differences for FIV. In typical cat populations with seroprevalence of 1-5%, a majority of positive results reported by most point-of-care test devices would be false-positives. This could result in unnecessary segregation or even euthanasia. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Stuetzer, Bianca; Brunner, Konstanze; Lutz, Hans; Hartmann, Katrin
2013-08-01
Feline leukaemia virus (FeLV) infection is still one of the leading causes of infection-related deaths in domestic cats. Treatment with various drugs has been attempted, but none has resulted in cure or complete virus elimination. Human interferon-α2a (huIFN-α2a) and 3'-azido-2',3'-dideoxythymidine (AZT) have been proven to decrease antigenaemia in cats infected experimentally with FeLV. The purpose of this study was to assess the efficacy of huIFN-α2a, AZT and a combination of both drugs in cats infected naturally with FeLV in a placebo-controlled double-blinded trial. Fourty-four FeLV-infected cats in which free FeLV p27 antigen was detected in serum by enzyme-linked immunosorbent assay were included in the study. Cats were assigned to one of four treatment groups that received either high dose huIFN-α2a (10(5) IU/kg q24h; 12 cats), AZT (5 mg/kg q12h; 10 cats, both of these treatments (12 cats) or placebo (10 cats). All cats were treated for 6 weeks. Clinical variables, including stomatitis, and laboratory parameters, such as CD4(+) and CD8(+) counts and serum FeLV p 27 antigen concentration, were recorded throughout the treatment period. No significant difference among the groups was observed during the treatment period for any of the parameters. Aside from anaemia in one cat treated with AZT, no adverse effects were observed. It was not possible to demonstrate efficacy of huIFN-α2a or AZT alone or together in cats infected naturally with FeLV when given according to this regimen for 6 weeks; however, no notable side effects were detected.
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Contijoch, Francisco; Witschey, Walter R T; Rogers, Kelly; Rears, Hannah; Hansen, Michael; Yushkevich, Paul; Gorman, Joseph; Gorman, Robert C; Han, Yuchi
2015-05-21
Data obtained during arrhythmia is retained in real-time cardiovascular magnetic resonance (rt-CMR), but there is limited and inconsistent evidence to show that rt-CMR can accurately assess beat-to-beat variation in left ventricular (LV) function or during an arrhythmia. Multi-slice, short axis cine and real-time golden-angle radial CMR data was collected in 22 clinical patients (18 in sinus rhythm and 4 patients with arrhythmia). A user-initialized active contour segmentation (ACS) software was validated via comparison to manual segmentation on clinically accepted software. For each image in the 2D acquisitions, slice volume was calculated and global LV volumes were estimated via summation across the LV using multiple slices. Real-time imaging data was reconstructed using different image exposure times and frame rates to evaluate the effect of temporal resolution on measured function in each slice via ACS. Finally, global volumetric function of ectopic and non-ectopic beats was measured using ACS in patients with arrhythmias. ACS provides global LV volume measurements that are not significantly different from manual quantification of retrospectively gated cine images in sinus rhythm patients. With an exposure time of 95.2 ms and a frame rate of > 89 frames per second, golden-angle real-time imaging accurately captures hemodynamic function over a range of patient heart rates. In four patients with frequent ectopic contractions, initial quantification of the impact of ectopic beats on hemodynamic function was demonstrated. User-initialized active contours and golden-angle real-time radial CMR can be used to determine time-varying LV function in patients. These methods will be very useful for the assessment of LV function in patients with frequent arrhythmias.
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Karabelas, Elias; Gsell, Matthias A. F.; Augustin, Christoph M.; Marx, Laura; Neic, Aurel; Prassl, Anton J.; Goubergrits, Leonid; Kuehne, Titus; Plank, Gernot
2018-01-01
Computational fluid dynamics (CFD) models of blood flow in the left ventricle (LV) and aorta are important tools for analyzing the mechanistic links between myocardial deformation and flow patterns. Typically, the use of image-based kinematic CFD models prevails in applications such as predicting the acute response to interventions which alter LV afterload conditions. However, such models are limited in their ability to analyze any impacts upon LV load or key biomarkers known to be implicated in driving remodeling processes as LV function is not accounted for in a mechanistic sense. This study addresses these limitations by reporting on progress made toward a novel electro-mechano-fluidic (EMF) model that represents the entire physics of LV electromechanics (EM) based on first principles. A biophysically detailed finite element (FE) model of LV EM was coupled with a FE-based CFD solver for moving domains using an arbitrary Eulerian-Lagrangian (ALE) formulation. Two clinical cases of patients suffering from aortic coarctations (CoA) were built and parameterized based on clinical data under pre-treatment conditions. For one patient case simulations under post-treatment conditions after geometric repair of CoA by a virtual stenting procedure were compared against pre-treatment results. Numerical stability of the approach was demonstrated by analyzing mesh quality and solver performance under the significantly large deformations of the LV blood pool. Further, computational tractability and compatibility with clinical time scales were investigated by performing strong scaling benchmarks up to 1536 compute cores. The overall cost of the entire workflow for building, fitting and executing EMF simulations was comparable to those reported for image-based kinematic models, suggesting that EMF models show potential of evolving into a viable clinical research tool. PMID:29892227
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Gao, Xiao-Ming; Dilley, Rodney J; Samuel, Chrishan S; Percy, Elodie; Fullerton, Meryl J; Dart, Anthony M; Du, Xiao-Jun
2002-10-01
This paper addresses whether the enhanced left ventricular (LV) contractility and heart rate, seen in transgenic mice overexpressing beta -adrenergic receptor in the heart, might raise the incidence of LV rupture after myocardial infarct. Transgenic and wild-type mice underwent left coronary artery occlusion. Postinfarct deaths that occurred 1-7 days after surgery were analyzed. Hemodynamics, morphologic parameters, and collagen content in the LV were determined. A significantly lower incidence of LV rupture was observed in transgenic than in wild-type mice 3-5 days after myocardial infarct (2.5 versus 19.7%, p < 0.05), despite a similar infarct size between the two groups and better hemodynamic function in transgenic mouse hearts. Morphologic analysis showed a more severe infarct expansion in wild-type versus transgenic mice or in mice dying of rupture versus those that died of acute heart failure. Collagen content was higher in the LV of sham-operated transgenic than wild-type mice (p < 0.01) with both type I and type III collagen elevated. Such difference in collagen content between transgenic and wild-type mice was maintained in noninfarcted and infarcted LV. In conclusion, transgenic mice overexpressing beta -adrenergic receptor had a lower risk of cardiac rupture during the acute phase after infarction despite the markedly enhanced LV contractility and heart rate. As a hyperdynamic function due to beta-adrenergic activation would likely increase the risk of cardiac rupture and infarct expansion, the lack of rupture in this transgenic mouse model suggests that the interstitial collagen level is a more important factor than functional status in the pathogenesis of rupture and infarct expansion.