Wang, Yan; Cao, Li; Liang, Dong; Meng, Lulu; Wu, Yun; Qiao, Fengchang; Ji, Xiuqing; Luo, Chunyu; Zhang, Jingjing; Xu, Tianhui; Yu, Bin; Wang, Leilei; Wang, Ting; Pan, Qiong; Ma, Dingyuan; Hu, Ping; Xu, Zhengfeng
2018-02-01
Currently, chromosomal microarray analysis is considered the first-tier test in pediatric care and prenatal diagnosis. However, the diagnostic yield of chromosomal microarray analysis for prenatal diagnosis of congenital heart disease has not been evaluated based on a large cohort. Our aim was to evaluate the clinical utility of chromosomal microarray as the first-tier test for chromosomal abnormalities in fetuses with congenital heart disease. In this prospective study, 602 prenatal cases of congenital heart disease were investigated using single nucleotide polymorphism array over a 5-year period. Overall, pathogenic chromosomal abnormalities were identified in 125 (20.8%) of 602 prenatal cases of congenital heart disease, with 52.0% of them being numerical chromosomal abnormalities. The detection rates of likely pathogenic copy number variations and variants of uncertain significance were 1.3% and 6.0%, respectively. The detection rate of pathogenic chromosomal abnormalities in congenital heart disease plus additional structural anomalies (48.9% vs 14.3%, P < .0001) or intrauterine growth retardation group (50.0% vs 14.3%, P = .044) was significantly higher than that in isolated congenital heart disease group. Additionally, the detection rate in congenital heart disease with additional structural anomalies group was significantly higher than that in congenital heart disease with soft markers group (48.9% vs 19.8%, P < .0001). No significant difference was observed in the detection rates between congenital heart disease with additional structural anomalies and congenital heart disease with intrauterine growth retardation groups (48.9% vs 50.0%), congenital heart disease with soft markers and congenital heart disease with intrauterine growth retardation groups (19.8% vs 50.0%), or congenital heart disease with soft markers and isolated congenital heart disease groups (19.8% vs 14.3%). The detection rate in fetuses with congenital heart disease plus mild ventriculomegaly was significantly higher than in those with other types of soft markers (50.0% vs 15.6%, P < .05). Our study suggests chromosomal microarray analysis is a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.
Ahmad, Fareed; Mangano, Robert; Shore, Shirah; Polimenakos, Anastasios
2017-10-01
This is a case report of premature low birth weight infant with hypoplasia of left heart structures and a large malaligned VSD who underwent successful staged approach of biventricular repair. We obtained qualitative and quantitative echocardiographic, MRI, and conventional catheterization data to support stepwise strategy towards LV rehabilitation to sustain adequate cardiac output. A thorough and intense follow-up has shown significant growth of left heart structures and favorable clinical status following staged biventricular repair. Our data indicate usefulness of qualitative and quantitative advanced complimentary multi-imaging modalities in predicting the postnatal growth potential of critically underdeveloped left heart structures.
Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.
Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika
2018-02-01
Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.
Bioengineering and Stem Cell Technology in the Treatment of Congenital Heart Disease
Bosman, Alexis; Edel, Michael J.; Blue, Gillian; Dilley, Rodney J.; Harvey, Richard P.; Winlaw, David S.
2015-01-01
Congenital heart disease places a significant burden on the individual, family and community despite significant advances in our understanding of aetiology and treatment. Early research in ischaemic heart disease has paved the way for stem cell technology and bioengineering, which promises to improve both structural and functional aspects of disease. Stem cell therapy has demonstrated significant improvements in cardiac function in adults with ischaemic heart disease. This finding, together with promising case studies in the paediatric setting, demonstrates the potential for this treatment in congenital heart disease. Furthermore, induced pluripotent stems cell technology, provides a unique opportunity to address aetiological, as well as therapeutic, aspects of disease. PMID:26239354
ERIC Educational Resources Information Center
Crowley, Julianne; Titmus, Morgan
2016-01-01
This article explores an alternative conception held by high school and first-year university biology students regarding the structure of the left and right ventricles of the heart and the significance of the left ventricular wall being thicker than the right. The left ventricular wall of the heart is thicker than the right ventricular wall due to…
Wang, Yu; Cao, Hai-yan; Xie, Ming-xing; He, Lin; Han, Wei; Hong, Liu; Peng, Yuan; Hu, Yun-fei; Song, Ben-cai; Wang, Jing; Wang, Bin; Deng, Cheng
2016-04-01
To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease (control group) and 18 specimens with severe congenital heart disease (case group) from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels (including overall level, atrioventricular and great vascular system, left-sided and right-sided heart), as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group (P=0.027). Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group (P=0.046), while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.
Diab, Osama Ali; Amer, Mohammed Said; Salah El-Din, Rania Ahmed
2016-12-01
To study the effect of coronary sinus (CS) occlusion on normal hearts and hearts with structural disease. We included 32 dogs, divided into 4 groups: (1) CS ligation (CSL): subjected to CSL; (2) control group: no intervention; (3) MI-CSL group: subjected to myocardial infarction (MI) induction followed by CSL after 1 week; and (4) MI-control group: subjected to MI induction, then open thoracotomy after 1 week without CSL. Electrocardiography, echocardiography, histopathology, and immunohistochemistry were done before and after CSL. In CSL group, there were no significant electrocardiographic or echocardiographic changes after CSL, although there was interstitial oedema that decreased after 1 week with the appearance of Thebesian vessels and positive staining for vascular endothelial growth factor. In MI-CSL group, there was significant increase in left ventricular (LV) end-systolic diameter (P = 02), decrease in LV fractional shortening (P = 0.0001), and LV ejection fraction (P = 0.002) in comparison with MI-control group, associated with severe myocardial degeneration. Acute CS occlusion could be compensated in normal hearts, but may be detrimental in the presence of structural heart disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
Left atrial function in heart failure with impaired and preserved ejection fraction.
Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man
2014-09-01
Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.
Meurs, Kathryn M; Stern, Josh A; Reina-Doreste, Yamir; Maran, Brian A; Chdid, Lhoucine; Lahmers, Sunshine; Keene, Bruce W; Mealey, Katrina L
2015-09-01
β-Adrenergic receptor antagonists are widely utilized for the management of cardiac diseases in dogs. We have recently identified two deletion polymorphisms in the canine adrenoreceptor 1 (ADRB1) gene.We hypothesized that canine ADRB1 deletions would alter the structure of the protein, as well as the heart rate response to the β-adrenergic receptor antagonist, atenolol. The objectives of this study were to predict the impact of these deletions on the predicted structure of the protein and on the heart rate response to atenolol in a population of healthy adult dogs. Eighteen apparently healthy, mature dogs with (11) and without (seven) ADRB1 deletions were evaluated. The heart rate of the dogs was evaluated with a baseline ambulatory ECG before and 14-21 days after atenolol therapy (1 mg/kg orally q12 h). Minimum, average, and maximum heart rates were compared between groups of dogs (deletions, controls) using an unpaired t-test and within each group of dogs using a paired t-test. The protein structure of ADRB1 was predicted by computer modeling. Deletions were predicted to alter the structure of the ADRB1 protein. The heart rates of the dogs with deletions were lower than those of the control dogs (the average heart rates were significantly lower). ADRB1 deletions appear to have structural and functional consequences. Individual genome-based treatment recommendations could impact the management of dogs with heart disease.
Hyperthyroidism and the Heart.
Osuna, Patricia Mejia; Udovcic, Maja; Sharma, Morali D
2017-01-01
Thyroid hormones have a significant impact on cardiac function and structure. Excess thyroid hormone affects cardiovascular hemodynamics, leading to high-output heart failure and, in late stages, dilated cardiomyopathy. In this review, we discuss how hyperthyroidism affects cardiovascular pathophysiology and molecular mechanisms and examine the complications caused by excess thyroid hormone, such as heart failure and atrial fibrillation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhukov, Mikhail, E-mail: cloudjyk@yandex.ru; Golubok, Alexander; Institute for Analytical Instrumentation, Russian Academy of Sciences
The new specialized AFM-probes with hydroxyapatite structures for atomic force microscopy of heart tissues calcification were created and studied. A process of probe fabrication is demonstrated. The adhesive forces between specialized hydroxyapatite probe and endothelium/subendothelial layers were investigated. It was found that the adhesion forces are significantly higher for the subendothelial layers. We consider that it is connected with the formation and localization of hydroxyapatite in the area of subendothelial layers of heart tissues. In addition, the roughness analysis and structure visualization of the endothelial surface of the heart tissue were carried out. The results show high efficiency of createdmore » specialized probes at study a calcinations process of the aortic heart tissues.« less
Rosa-Garrido, Manuel; Chapski, Douglas J.; Schmitt, Anthony D.; Kimball, Todd H.; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J.; Ren, Shuxun; Wang, Yibin; Ren, Bing
2017-01-01
Background: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. Methods: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload–induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Results: Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. Conclusions: These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. PMID:28802249
Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M
2017-10-24
Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.
Polarization-resolved SHG microscopy in cardiac hypertrophy study (Conference Presentation)
NASA Astrophysics Data System (ADS)
Wang, Zhonghai; Yuan, Cai; Shao, Yonghong; Bradshaw, Amy D.; Borg, Thomas K.; Gao, Bruce Z.
2017-02-01
Cardiac hypertrophy, a process initiated by mechanical alterations, is hypothesized to cause long-term molecular-level alteration in the sarcomere lattice, which is the main force-generating component in the heart muscle. This molecular-level alteration is beyond the resolving capacity of common light microscopy. Second harmonic generation (SHG) microscopy has unique capability for visualizing ordered molecular structures in biological tissues without labeling. Combined with polarization imaging technique, SHG microscopy is able to extract structural details of myosin at the molecular level so as to reveal molecular-level alterations that occur during hypertrophy. The myosin filaments are believed to possess C6 symmetry; thus, the nonlinear polarization response relationship between generated second harmonic light I^2ωand incident fundamental light I^ω is determined by nonlinear coefficients, χ_15, χ_31 and χ_33. χ_31/χ_15 is believed to be an indicator of the molecular symmetry of myosin filament, whileχ_33/χ_15represents the intramyosin orientation angle of the double helix. By changing the polarization of the incident light and evaluating the corresponding SHG signals, the molecular structure of the myosin, reflected by the χ coefficients, can be revealed. With this method, we studied the structural properties of heart tissues in different conditions, including those in normal, physiologically hypertrophic (heart tissue from postpartum female rats), and pathologically hypertrophic (heart tissue from transverse-aorta constricted rats) conditions. We found that ratios of χ_31/χ_15 showed no significant difference between heart tissues from different conditions; their values were all close to 1, which demonstrated that Kleinman symmetry held for all conditions. Ratios of χ_33/χ_15 from physiologically or pathologically hypertrophic heart tissues were raised and showed significant difference from those from normal heart tissues, which indicated that the intramyosin orientation angle of the double helix was altered when heart tissues hypertrophied. Polarization-resolved SHG microscopy permitted us to study heart tissues at the molecular level and may serve as a diagnostic tool for cardiac hypertrophy.
Osuna, Patricia Mejia; Udovcic, Maja; Sharma, Morali D.
2017-01-01
Thyroid hormones have a significant impact on cardiac function and structure. Excess thyroid hormone affects cardiovascular hemodynamics, leading to high-output heart failure and, in late stages, dilated cardiomyopathy. In this review, we discuss how hyperthyroidism affects cardiovascular pathophysiology and molecular mechanisms and examine the complications caused by excess thyroid hormone, such as heart failure and atrial fibrillation. PMID:28740583
Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie
2018-04-01
The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p < 0.001) higher collagen I content, a lower collagen III and elastin content, and a similar glycosaminoglycans (GAGs) content, in comparison with the NAV, as measured by ECM integrated density. However, the relative thickness of the main load-bearing structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p < 0.05) than in the longitudinal direction. This proved that both tissues were anisotropic. No statistically significant differences in UTS (ultimate tensile strength) values and in calculated bending stiffness values in the longitudinal or transversal direction were found between HP and NAV. Our study confirms that HP has an advantageous ECM biopolymeric structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.
Epinephrine and left atrial and left ventricular diastolic function decrease in normal subjects.
Fuenmayor, Abdel J; Solórzano, Moisés I; Gómez, Luisangelly
2016-10-01
We assessed the effect of epinephrine over left atrial and left ventricular diastolic function in subjects without structural heart disease. Twenty-seven, 34.6±17.2year-old patients without structural heart disease were included. Intravenous epinephrine (50 to 100ng/kg/min) was infused. Left atrial and ventricular functions were evaluated by means of echocardiography before and during the epinephrine infusion. No complications were observed. Significant increases in heart rate and systolic blood pressure were recorded. Both left atrial (minimal and maximal) volumes increased but increase in the minimal volume was more pronounced, and the ejection fraction diminished. Left atrial expansion index decreased and the fraction of left ventricular inflow volume resulting from atrial contraction increased. Two patients displayed abnormal left ventricular diastolic function. During epinephrine infusion, E/A and e' decreased, and isovolumetric relaxation time increased. In this group of young adults without structural heart disease, epinephrine infusion was safe, did not produce any complications, and induced a small but significant decrease in left atrial function and left ventricular diastolic function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Cellular Plasticity in the Diabetic Myocardium
2017-09-01
pathogenesis of cardiac dysfunction associated with metabolic disease . 8 Fig. 1: The db/db mouse recapitulates features of human Heart failure with ...patients, hypertensive heart disease is associated with development of interstitial and periarteriolar fibrosis even in the absence of significant cor...increased secretion of structural matrix proteins. The cardiac ECM in metabolic disease Diabetics exhibit a high incidence of heart failure with
Noda, Takashi; Kurita, Takashi; Nitta, Takashi; Chiba, Yasutaka; Furushima, Hiroshi; Matsumoto, Naoki; Toyoshima, Takeshi; Shimizu, Akihiko; Mitamura, Hideo; Okumura, Ken; Ohe, Tohru; Aizawa, Yoshifusa
2018-03-15
Electrical storm (E-Storm), defined as multiple episodes of ventricular arrhythmias within a short period of time, is an important clinical problem in patients with an implantable cardiac defibrillator (ICD) including cardiac resynchronization therapy devices capable of defibrillation. The detailed clinical aspects of E-Storm in large populations especially for non-ischemic dilated cardiomyopathy (DCM), however, remain unclear. This study was performed to elucidate the detailed clinical aspects of E-Storm, such as its predictors and prevalence among patients with structural heart disease including DCM. We analyzed the data of the Nippon Storm Study, which was a prospective observational study involving 1570 patients enrolled from 48 ICD centers. For the purpose of this study, we evaluated 1274 patients with structural heart disease, including 482 (38%) patients with ischemic heart disease (IHD) and 342 (27%) patients with DCM. During a median follow-up of 28months (interquartile range: 23 to 33months), E-Storm occurred in 84 (6.6%) patients. The incidence of E-Storm was not significantly different between patients with IHD and patients with DCM (log-rank p=0.52). Proportional hazard regression analyses showed that ICD implantation for secondary prevention of sudden cardiac death (p=0.0001) and QRS width (p=0.015) were the independent risk factors for E-storm. In a comparison between patients with and without E-Storm, survival curves after adjustment for clinical characteristics showed a significant difference in mortality. E-Storm was associated with subsequent mortality in patients with structural heart disease including DCM. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Hypertension as a risk factor for heart failure.
Kannan, Arun; Janardhanan, Rajesh
2014-07-01
Hypertension remains a significant risk factor for development of congestive heart failure CHF), with various mechanisms contributing to both systolic and diastolic dysfunction. The pathogenesis of myocardial changes includes structural remodeling, left ventricular hypertrophy, and fibrosis. Activation of the sympathetic nervous system and renin-angiotensin system is a key contributing factor of hypertension, and thus interventions that antagonize these systems promote regression of hypertrophy and heart failure. Control of blood pressure is of paramount importance in improving the prognosis of patients with heart failure.
The Athletic Heart Syndrome: Ruling Out Cardiac Pathologies.
ERIC Educational Resources Information Center
Puffer, James C.
2002-01-01
People who participate in regular vigorous or strenuous physical activities undergo significant changes in cardiac structure and function. Occasionally, these changes may be confused with those of hypertrophic cardiomyopathy (HCM). Differentiating between athletic heart syndrome and HCM requires careful examination. ECG and echocardiograms may be…
Matrone, Gianfranco; Wilson, Kathryn S; Mullins, John J; Tucker, Carl S; Denvir, Martin A
2015-06-01
Heart formation is a complex, dynamic and highly coordinated process of molecular, morphogenetic and functional factors with each interacting and contributing to formation of the mature organ. Cardiac abnormalities in early life can be lethal in mammals but not in the zebrafish embryo which has been widely used to study the developing heart. While early cardiac development in the zebrafish has been well characterized, functional changes during development and how these relate to architectural, cellular and molecular aspects of development have not been well described previously. To address this we have carefully characterised cardiac structure, function, cardiomyocyte proliferation and cardiac-specific gene expression between 48 and 120 hpf in the zebrafish. We show that the zebrafish heart increases in volume and changes shape significantly between 48 and 72 hpf accompanied by a 40% increase in cardiomyocyte number. Between 96 and 120 hpf, while external heart expansion slows, there is rapid formation of a mature and extensive trabecular network within the ventricle chamber. While ejection fraction does not change during the course of development other determinants of contractile function increase significantly particularly between 72 and 96 hpf leading to an increase in cardinal vein blood flow. This study has revealed a number of novel aspects of cardiac developmental dynamics with striking temporal orchestration of structure and function within the first few days of development. These changes are associated with changes in expression of developmental and maturational genes. This study provides important insights into the complex temporal relationship between structure and function of the developing zebrafish heart. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
TRPV2 is critical for the maintenance of cardiac structure and function in mice
Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji
2014-01-01
The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca2+ handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca2+-dependent intracellular Ca2+ increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function. PMID:24874017
TRPV2 is critical for the maintenance of cardiac structure and function in mice.
Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji
2014-05-29
The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca(2+) handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca(2+)-dependent intracellular Ca(2+) increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function.
Levay, Agata K; Peacock, Jacqueline D; Lu, Yinhui; Koch, Manuel; Hinton, Robert B; Kadler, Karl E; Lincoln, Joy
2008-10-24
Heart valve structures, derived from mesenchyme precursor cells, are composed of differentiated cell types and extracellular matrix arranged to facilitate valve function. Scleraxis (scx) is a transcription factor required for tendon cell differentiation and matrix organization. This study identified high levels of scx expression in remodeling heart valve structures at embryonic day 15.5 through postnatal stages using scx-GFP reporter mice and determined the in vivo function using mice null for scx. Scx(-/-) mice display significantly thickened heart valve structures from embryonic day 17.5, and valves from mutant mice show alterations in valve precursor cell differentiation and matrix organization. This is indicated by decreased expression of the tendon-related collagen type XIV, increased expression of cartilage-associated genes including sox9, as well as persistent expression of mesenchyme cell markers including msx1 and snai1. In addition, ultrastructure analysis reveals disarray of extracellular matrix and collagen fiber organization within the valve leaflet. Thickened valve structures and increased expression of matrix remodeling genes characteristic of human heart valve disease are observed in juvenile scx(-/-) mice. In addition, excessive collagen deposition in annular structures within the atrioventricular junction is observed. Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures.
Atrial Fibrillation and Heart Failure - Cause or Effect?
Prabhu, Sandeep; Voskoboinik, Aleksandr; Kaye, David M; Kistler, Peter M
2017-09-01
There are emerging epidemics of atrial fibrillation (AF) and heart failure in most developed countries, with a significant health burden. Due to many shared pathophysiological mechanisms, which facilitate the maintenance of each condition, AF and heart failure co-exist in up to 30% of patients. In the circumstance where known structural causes of heart failure (such as myocardial infarction) are absent, patients presenting with both conditions present a unique challenge, particularly as the temporal relationship of each condition can often remain elusive from the clinical history. The question of whether the AF is driving, or significantly contributing to the left ventricular (LV) dysfunction, rather than merely a consequence of heart failure, has become ever more pertinent, especially as catheter ablation now offers a significant advancement over existing rhythm control strategies. This paper will review the inter-related physiological drivers of AF and heart failure before considering the implications from the outcomes of recent clinical trials in patients with AF and heart failure. Copyright © 2017 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.
Rezaei, Ali; Heidarian, Esfandiar
2013-08-01
The administration of flaxseed oil or flaxseed oil plus trientine in diabetic rats reduced triglyceride, very low density lipoprotein, and total cholesterol. Furthermore, the combined treatment significantly increased superoxide dismutase activity and attenuated serum Cu2+. The results suggest that the administration of flaxseed oil plus trientine is useful in controlling serum lipid abnormalities, oxidative stress, restoring heart structure, and reducing serum Cu2+ in diabetic rats.
Comorbid Conditions in Neonates With Congenital Heart Disease.
Krishnamurthy, Ganga; Ratner, Veniamin; Bacha, Emile; Aspelund, Gudrun
2016-08-01
The objectives of this review are to discuss the pathophysiology, clinical impact and treatment of major noncardiac anomalies, and prematurity in infants with congenital heart disease. MEDLINE and PubMed. Mortality risk is significantly higher in patients with congenital heart disease and associated anomalies compared with those in whom the heart defect occurs in isolation. Although most noncardiac structural anomalies do not require surgery in the neonatal period, several require surgery for survival. Management of such infants poses multiple challenges. Premature infants with congenital heart disease face challenges imposed by their immature organ systems, which are susceptible to injury or altered function by congenital heart disease and abnormal circulatory physiology independent of congenital heart disease. For optimal outcomes in premature infants or in infants with multiple congenital anomalies, a collaborative interdisciplinary approach is necessary.
Wang, Linlin; Li, Yuanmin; Deng, Wen; Dong, Zhihui; Li, Xue; Liu, Dan; Zhao, Lijie; Fu, Weiguo; Cho, Kenka; Niu, Huaying; Guo, Dean; Cheng, Jinle; Jiang, Baohong
2018-08-10
Myocardial infarction (MI) is considered as the major inducer to the morbidity and mortality related to coronary occlusion. Salvia miltiorrhiza Bunge is widely applied in the clinic for the prevention and treatment of heart diseases. The preparation of traditional herb decoction (THD) is not only time consuming but also difficult to keep uniform for every time. New usage form of Salvia miltiorrhiza Bunge with characteristics of convenience, uniform and efficiency is needed. The aims of present study were to investigate the cardio-protection of ultrafine granular powder (UGP) of Salvia miltiorrhiza Bunge; and further compare the characteristics of UGP with THD. MI was induced by ligation of the left anterior descending coronary artery near the main pulmonary artery. Cardio-protection of UGP or THD was evaluated based on two sets of experiments, one was acute myocardial infarction (AMI) through 7 days preventive administration, and the other one was chronic cardiac remodeling through 28 days therapeutic administration. Hemodynamic measurement was conducted to evaluate heart function and histopathological detection was used to evaluate heart structure. No significant improvement of heart structure and function was detected for preventive administration of UGP or THD on AMI rats. While, more significant improvements on left ventricular systolic and diastolic function were detected with therapeutic treatment with 0.81 g/kg UGP than same dose of THD on rats against chronic cardiac remodeling. Both UGP and THD showed the protective effects on heart structure, especially against fibrosis with long-term therapeutic treatment. As a new usage form of Salvia miltiorrhiza Bunge, UGP showed significant cardio-protection against myocardial remodeling with therapeutic treatment. Comparing with THD, UGP also holds the advantages of uniform, convenience and efficiency. Copyright © 2018 Elsevier B.V. All rights reserved.
Structured telephone support or non-invasive telemonitoring for patients with heart failure.
Inglis, Sally C; Clark, Robyn A; Dierckx, Riet; Prieto-Merino, David; Cleland, John G F
2015-10-31
Specialised disease management programmes for heart failure aim to improve care, clinical outcomes and/or reduce healthcare utilisation. Since the last version of this review in 2010, several new trials of structured telephone support and non-invasive home telemonitoring have been published which have raised questions about their effectiveness. To review randomised controlled trials (RCTs) of structured telephone support or non-invasive home telemonitoring compared to standard practice for people with heart failure, in order to quantify the effects of these interventions over and above usual care. We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology AsseFssment Database (HTA) on the Cochrane Library; MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index- Science (CPCI-S) on Web of Science (Thomson Reuters), AMED, Proquest Theses and Dissertations, IEEE Xplore and TROVE in January 2015. We handsearched bibliographies of relevant studies and systematic reviews and abstract conference proceedings. We applied no language limits. We included only peer-reviewed, published RCTs comparing structured telephone support or non-invasive home telemonitoring to usual care of people with chronic heart failure. The intervention or usual care could not include protocol-driven home visits or more intensive than usual (typically four to six weeks) clinic follow-up. We present data as risk ratios (RRs) with 95% confidence intervals (CIs). Primary outcomes included all-cause mortality, all-cause and heart failure-related hospitalisations, which we analysed using a fixed-effect model. Other outcomes included length of stay, health-related quality of life, heart failure knowledge and self care, acceptability and cost; we described and tabulated these. We performed meta-regression to assess homogeneity (the null hypothesis) in each subgroup analysis and to see if the effect of the intervention varied according to some quantitative variable (such as year of publication or median age). We include 41 studies of either structured telephone support or non-invasive home telemonitoring for people with heart failure, of which 17 were new and 24 had been included in the previous Cochrane review. In the current review, 25 studies evaluated structured telephone support (eight new studies, plus one study previously included but classified as telemonitoring; total of 9332 participants), 18 evaluated telemonitoring (nine new studies; total of 3860 participants). Two of the included studies trialled both structured telephone support and telemonitoring compared to usual care, therefore 43 comparisons are evident.Non-invasive telemonitoring reduced all-cause mortality (RR 0.80, 95% CI 0.68 to 0.94; participants = 3740; studies = 17; I² = 24%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.71, 95% CI 0.60 to 0.83; participants = 2148; studies = 8; I² = 20%, GRADE: moderate-quality evidence). Structured telephone support reduced all-cause mortality (RR 0.87, 95% CI 0.77 to 0.98; participants = 9222; studies = 22; I² = 0%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.85, 95% CI 0.77 to 0.93; participants = 7030; studies = 16; I² = 27%, GRADE: moderate-quality evidence).Neither structured telephone support nor telemonitoring demonstrated effectiveness in reducing the risk of all-cause hospitalisations (structured telephone support: RR 0.95, 95% CI 0.90 to 1.00; participants = 7216; studies = 16; I² = 47%, GRADE: very low-quality evidence; non-invasive telemonitoring: RR 0.95, 95% CI 0.89 to 1.01; participants = 3332; studies = 13; I² = 71%, GRADE: very low-quality evidence).Seven structured telephone support studies reported length of stay, with one reporting a significant reduction in length of stay in hospital. Nine telemonitoring studies reported length of stay outcome, with one study reporting a significant reduction in the length of stay with the intervention. One telemonitoring study reported a large difference in the total number of hospitalisations for more than three days, but this was not an analysis of length of stay per hospitalisation. Nine of 11 structured telephone support studies and five of 11 telemonitoring studies reported significant improvements in health-related quality of life. Nine structured telephone support studies and six telemonitoring studies reported costs of the intervention or cost effectiveness. Three structured telephone support studies and one telemonitoring study reported a decrease in costs and two telemonitoring studies reported increases in cost, due both to the cost of the intervention and to increased medical management. Adherence was rated between 55.1% and 98.5% for those structured telephone support and telemonitoring studies which reported this outcome. Participant acceptance of the intervention was reported in the range of 76% to 97% for studies which evaluated this outcome. Seven of nine studies that measured these outcomes reported significant improvements in heart failure knowledge and self-care behaviours. For people with heart failure, structured telephone support and non-invasive home telemonitoring reduce the risk of all-cause mortality and heart failure-related hospitalisations; these interventions also demonstrated improvements in health-related quality of life and heart failure knowledge and self-care behaviours. Studies also demonstrated participant satisfaction with the majority of the interventions which assessed this outcome.
Li, Airong; Ahsen, Osman O.; Liu, Jonathan J.; Du, Chuang; McKee, Mary L.; Yang, Yan; Wasco, Wilma; Newton-Cheh, Christopher H.; O'Donnell, Christopher J.; Fujimoto, James G.; Zhou, Chao; Tanzi, Rudolph E.
2013-01-01
The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits. PMID:23696452
Li, Airong; Ahsen, Osman O; Liu, Jonathan J; Du, Chuang; McKee, Mary L; Yang, Yan; Wasco, Wilma; Newton-Cheh, Christopher H; O'Donnell, Christopher J; Fujimoto, James G; Zhou, Chao; Tanzi, Rudolph E
2013-09-15
The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits.
Exercise echocardiography for structural heart disease.
Izumo, Masaki; Akashi, Yoshihiro J
2016-03-01
Since the introduction of transcatheter structural heart intervention, the term "structural heart disease" has been widely used in the field of cardiology. Structural heart disease refers to congenital heart disease, valvular heart disease, and cardiomyopathy. In structural heart disease, valvular heart disease is frequently identified in the elderly. Of note, the number of patients who suffer from aortic stenosis (AS) and mitral regurgitation (MR) is increasing in developed countries because of the aging of the populations. Transcatheter aortic valve replacement and percutaneous mitral valve repair has been widely used for AS and MR, individually. Echocardiography is the gold standard modality for initial diagnosis and subsequent evaluation of AS and MR, although the difficulties in assessing patients with these diseases still remain. Here, we review the clinical usefulness and prognostic impact of exercise echocardiography on structural heart disease, particularly on AS and MR.
Research on fiber Bragg grating heart sound sensing and wavelength demodulation method
NASA Astrophysics Data System (ADS)
Zhang, Cheng; Miao, Chang-Yun; Gao, Hua; Gan, Jing-Meng; Li, Hong-Qiang
2010-11-01
Heart sound includes a lot of physiological and pathological information of heart and blood vessel. Heart sound detecting is an important method to gain the heart status, and has important significance to early diagnoses of cardiopathy. In order to improve sensitivity and reduce noise, a heart sound measurement method based on fiber Bragg grating was researched. By the vibration principle of plane round diaphragm, a heart sound sensor structure of fiber Bragg grating was designed and a heart sound sensing mathematical model was established. A formula of heart sound sensitivity was deduced and the theoretical sensitivity of the designed sensor is 957.11pm/KPa. Based on matched grating method, the experiment system was built, by which the excursion of reflected wavelength of the sensing grating was detected and the information of heart sound was obtained. Experiments show that the designed sensor can detect the heart sound and the reflected wavelength variety range is about 70pm. When the sampling frequency is 1 KHz, the extracted heart sound waveform by using the db4 wavelet has the same characteristics with a standard heart sound sensor.
Chloroquine-induced cardiomyopathy: a reversible cause of heart failure.
Yogasundaram, Haran; Hung, Whitney; Paterson, Ian D; Sergi, Consolato; Oudit, Gavin Y
2018-06-01
Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-rheumatic medications frequently used in the treatment of connective tissue disorders. We present the case of a 45-year-old woman with CQ-induced cardiomyopathy leading to severe heart failure. Electrocardiographic abnormalities included bifascicular block, while structural disease consisted of severe biventricular and biatrial hypertrophy. Appropriate diagnosis via endomyocardial biopsy led to cessation of CQ and subsequent dramatic improvement in symptoms and structural heart disease. Cardiac toxicity is an under-recognized adverse effect of CQ/HCQ leading to cardiomyopathy with concentric hypertrophy and conduction abnormalities, with the potential for significant morbidity and mortality. Predisposing factors for CQ/HCQ-induced cardiomyopathy have been proposed. CQ/HCQ cardiomyopathy is a phenocopy of Fabry disease, and α-galactosidase A polymorphism may account for some heterogeneity of disease presentation. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
NASA Astrophysics Data System (ADS)
Wang, Shang; Singh, Manmohan; Lopez, Andrew L.; Wu, Chen; Raghunathan, Raksha; Schill, Alexander; Li, Jiasong; Larin, Kirill V.; Larina, Irina V.
2016-03-01
Efficient phenotyping of cardiac dynamics in live mouse embryos has significant implications on understanding of early mammalian heart development and congenital cardiac defects. Recent studies established optical coherence tomography (OCT) as a powerful tool for live embryonic heart imaging in various animal models. However, current four-dimensional (4D) OCT imaging of the beating embryonic heart largely relies on gated data acquisition or postacquisition synchronization, which brings errors when cardiac cycles lack perfect periodicity and is time consuming and computationally expensive. Here, we report direct 4D OCT imaging of the structure and function of cardiac dynamics in live mouse embryos achieved by employing a Fourier domain mode-locking swept laser source that enables ~1.5 MHz A-line rate. Through utilizing both forward and backward scans of a resonant mirror, we obtained a ~6.4 kHz frame rate, which allows for a direct volumetric data acquisition speed of ~43 Hz, around 20 times of the early-stage mouse embryonic heart rate. Our experiments were performed on mouse embryos at embryonic day 9.5. Time-resolved 3D cardiodynamics clearly shows the heart structure in motion. We present analysis of cardiac wall movement and its velocity from the primitive atrium and ventricle. Our results suggest that the combination of ultrahigh-speed OCT imaging with live embryo culture could be a useful embryonic heart phenotyping approach for mouse mutants modeling human congenital heart diseases.
Khomaziuk, I M; Habulavichene, Zh M; Khomaziuk, V A
2011-01-01
Particularities and clinical importance of the structural and functional changes of myocardium were estimated in Chernobyl disaster clean-up workers with atrial fibrillation (AF). We examined 122 men with AF, which was associated with ischemic heart disease and arterial hypertension. Paroxysmal AF was diagnosed in 42 patients, 80 patients had permanent AE Control group comprised 80 men without AF. Echocardiography and Doppler studies were performed using ultrasound scanner Aloka SSD-630 (Japan). Significant structural and functional changes of the heart were revealed already in paroxysmal AF and became more pronounced in permanent AF. Increased left atrial size, its ratio to left ventricular end diastolic diameter, diastolic dysfunction were important echocardiographic predictors of AF. Heart walls thickening was accompanied by disorders of myocardial relaxation, increase in myocardial mass led to ischemia, and together they promoted overload, dysfunction of atrium and development of AF. Obligatory echocardiographic examination of the Chernobyl disaster clean-up workers with ischemic heart disease and arterial hypertension is necessary for predicting AF early, ordering adequate therapy in proper time and improving prognosis.
Stam, Barbara; Peulen, Heike; Guckenberger, Matthias; Mantel, Frederick; Hope, Andrew; Werner-Wasik, Maria; Belderbos, Jose; Grills, Inga; O'Connell, Nicolette; Sonke, Jan-Jakob
2017-06-01
To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). 803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively. Median follow-up was 34.8months. Two year Kaplan-Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009-197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003-70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death. Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied. Copyright © 2017 Elsevier B.V. All rights reserved.
Radiation-induced valvular heart disease.
Gujral, Dorothy M; Lloyd, Guy; Bhattacharyya, Sanjeev
2016-02-15
Radiation to the mediastinum is a key component of treatment with curative intent for a range of cancers including Hodgkin's lymphoma and breast cancer. Exposure to radiation is associated with a risk of radiation-induced heart valve damage characterised by valve fibrosis and calcification. There is a latent interval of 10-20 years between radiation exposure and development of clinically significant heart valve disease. Risk is related to radiation dose received, interval from exposure and use of concomitant chemotherapy. Long-term outlook and the risk of valve surgery are related to the effects of radiation on mediastinal structures including pulmonary fibrosis and pericardial constriction. Dose prediction models to predict the risk of heart valve disease in the future and newer radiation techniques to reduce the radiation dose to the heart are being developed. Surveillance strategies for this cohort of cancer survivors at risk of developing significant heart valve complications are required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Xia, Jun Hong; Li, Hong Lian; Li, Bi Jun; Gu, Xiao Hui; Lin, Hao Ran
2018-01-10
Hypoxia is one of the critical environmental stressors for fish in aquatic environments. Although accumulating evidences indicate that gene expression is regulated by hypoxia stress in fish, how genes undergoing differential gene expression and/or alternative splicing (AS) in response to hypoxia stress in heart are not well understood. Using RNA-seq, we surveyed and detected 289 differential expressed genes (DEG) and 103 genes that undergo differential usage of exons and splice junctions events (DUES) in heart of a hypoxia tolerant fish, Nile tilapia, Oreochromis niloticus following 12h hypoxic treatment. The spatio-temporal expression analysis validated the significant association of differential exon usages in two randomly selected DUES genes (fam162a and ndrg2) in 5 tissues (heart, liver, brain, gill and spleen) sampled at three time points (6h, 12h, and 24h) under acute hypoxia treatment. Functional analysis significantly associated the differential expressed genes with the categories related to energy conservation, protein synthesis and immune response. Different enrichment categories were found between the DEG and DUES dataset. The Isomerase activity, Oxidoreductase activity, Glycolysis and Oxidative stress process were significantly enriched for the DEG gene dataset, but the Structural constituent of ribosome and Structural molecule activity, Ribosomal protein and RNA binding protein were significantly enriched only for the DUES genes. Our comparative transcriptomic analysis reveals abundant stress responsive genes and their differential regulation function in the heart tissues of Nile tilapia under acute hypoxia stress. Our findings will facilitate future investigation on transcriptome complexity and AS regulation during hypoxia stress in fish. Copyright © 2017 Elsevier B.V. All rights reserved.
Iwasaki, Yu-Ki; Yamashita, Takeshi; Sekiguchi, Akiko; Hayami, Noriyuki; Shimizu, Wataru
2016-06-01
Hypertension is one of the independent risk factors for atrial fibrillation (AF). Pulmonary veins (PVs) play an important role as the substrate for AF and triggers of AF. The purpose of this study was to determine the structural remodelling of the PVs and its effect on promoting AF in hypertensive (HT) rat hearts. Eighteen-week-old Dahl salt-sensitive HT rats and their controls were used for histological and immunohistological analyses, and electrophysiological studies were performed in Langendorff perfused hearts. Masson-trichrome staining revealed that hypertension significantly increased the fibrosis in the PVs, particularly in subendocardial and perivascular areas, compared with that in control rats, however, at this early stage of hypertension, left atrial fibrosis was not prominent. In the HT rat hearts with PVs, electrical stimulation significantly increased the number of repetitive atrial firing and atrial tachycardia inducibility, which significantly diminished after the excision of the PVs. An immunofluorescent analysis revealed that HT rats had PV specific endocardial smooth muscle actin (αSMA)-positive cells with remarkable proliferation of platelet-derived growth factor (PDGF)-C and vascular endothelial growth factor (VEGF), which was lacking in the left atrial structures of the control and the HT rats. Pretreatment with imatinib, a PDGF receptor activity blocker, in HT rats reduced the αSMA-positive cell proliferation and fibrosis in the PVs and also induced a significant reduction in VEGF expression. Also, the drug pretreatment effectively prevented repetitive atrial firing promotion without affecting the blood pressure. PV preferential fibrosis might play an important role in the arrhythmogenic substrate of AF in HT rat hearts. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir
2017-01-01
The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.
Quantitative analysis of hypertrophic myocardium using diffusion tensor magnetic resonance imaging
Tran, Nicholas; Giannakidis, Archontis; Gullberg, Grant T.; Seo, Youngho
2016-01-01
Abstract. Systemic hypertension is a causative factor in left ventricular hypertrophy (LVH). This study is motivated by the potential to reverse or manage the dysfunction associated with structural remodeling of the myocardium in this pathology. Using diffusion tensor magnetic resonance imaging, we present an analysis of myocardial fiber and laminar sheet orientation in ex vivo hypertrophic (6 SHR) and normal (5 WKY) rat hearts using the covariance of the diffusion tensor. First, an atlas of normal cardiac microstructure was formed using the WKY b0 images. Then, the SHR and WKY b0 hearts were registered to the atlas. The acquired deformation fields were applied to the SHR and WKY heart tensor fields followed by the preservation of principal direction (PPD) reorientation strategy. A mean tensor field was then formed from the registered WKY tensor images. Calculating the covariance of the registered tensor images about this mean for each heart, the hypertrophic myocardium exhibited significantly increased myocardial fiber derangement (p=0.017) with a mean dispersion of 38.7 deg, and an increased dispersion of the laminar sheet normal (p=0.030) of 54.8 deg compared with 34.8 deg and 51.8 deg, respectively, in the normal hearts. Results demonstrate significantly altered myocardial fiber and laminar sheet structure in rats with hypertensive LVH. PMID:27872872
ACE phenotyping in human heart.
Tikhomirova, Victoria E; Kost, Olga A; Kryukova, Olga V; Golukhova, Elena Z; Bulaeva, Naida I; Zholbaeva, Aigerim Z; Bokeria, Leo A; Garcia, Joe G N; Danilov, Sergei M
2017-01-01
Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.
Cui, Weina; Jang, Albert; Zhang, Pengyuan; Thompson, Brian; Townsend, DeWayne; Metzger, Joseph M; Zhang, Jianyi
2015-01-01
Duchenne muscular dystrophy (DMD) is the most common fatal form of muscular dystrophy characterized by striated muscle wasting and dysfunction. Patients with DMD have a very high incidence of heart failure, which is increasingly the cause of death in DMD patients. We hypothesize that in the in vivo system, the dystrophic cardiac muscle displays bioenergetic deficits prior to any functional or structural deficits. To address this we developed a complete non invasive 31P magnetic resonance spectroscopy (31P MRS) approach to measure myocardial bioenergetics in the heart in vivo. Six control and nine mdx mice at 5 months of age were used for the study. A standard 3D -Image Selected In vivo Spectroscopy (3D-ISIS) sequence was used to provide complete gradient controlled three-dimensional localization for heart 31P MRS. These studies demonstrated dystrophic hearts have a significant reduction in PCr/ATP ratio compare to normal (1.59±0.13 vs 2.37±0.25, p<0.05). Our present study provides the direct evidence of significant cardiac bioenergetic deficits in the in vivo dystrophic mouse. These data suggest that energetic defects precede the development of significant hemodynamic or structural changes. The methods provide a clinically relevant approach to use myocardial energetics as an early marker of disease in the dystrophic heart. The new method in detecting the in vivo bioenergetics abnormality as an early non-invasive marker of emerging dystrophic cardiomyopathy is critical in management of patients with DMD, and optimized therapies aimed at slowing or reversing the cardiomyopathy.
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.
Disease management programs for heart failure: not just for the 'sick' heart failure population.
McDonald, Ken; Conlon, Carmel; Ledwidge, Mark
2007-02-01
The development of disease management programs has been a major advance in heart failure care, bringing about significant improvements for the heart failure population, with reduction in readmission, better use of guideline therapy and improved survival. However, at present, the majority of such programs focus their attention only on the sicker segment of this population, with little application of this important service to the broader heart failure population, where potentially benefits may be even more impressive. This has led to an imbalance in the care of patients with heart failure, where aspects of management such as regular structured review and education are preferentially given to the group at the later stages of the natural history of the syndrome. This paper argues for a far wider application of the disease management program concept in heart failure care so as to bring the benefits of specialist care, patient education and follow-up to patients at an earlier stage in the natural history of heart failure.
Cardiac Metabolism in Heart Failure - Implications beyond ATP production
Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale
2013-01-01
The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714
Chen, Jiqiu; Yaniz-Galende, Elisa; Kagan, Heather J.; Liang, Lifan; Hekmaty, Saboor; Giannarelli, Chiara
2015-01-01
The aim of the present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). CHF was induced in rats by aortic banding plus ischemia-reperfusion followed by aortic debanding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were obtained to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Stenosis was found in all levels of the coronary arteries in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in microvessels with a diameter of ≤3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, potentially indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in length in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart had lower functional reserve; this may be associated with congestion in coronary microcirculation. Ischemic coronary vascular disorder is not limited to the main coronary arteries, as it occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation, and roughened surfaces. This disorder in the coronary artery architecture may contribute to the reduction in myocyte contractility in the setting of heart failure. PMID:25659485
Mammalian enabled (Mena) is a critical regulator of cardiac function
Aguilar, Frédérick; Belmonte, Stephen L.; Ram, Rashmi; Noujaim, Sami F.; Dunaevsky, Olga; Protack, Tricia L.; Jalife, Jose; Todd Massey, H.; Gertler, Frank B.
2011-01-01
Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena−/−) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena−/− mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena−/− hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena−/− mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction. PMID:21335464
Mammalian enabled (Mena) is a critical regulator of cardiac function.
Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C
2011-05-01
Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.
Kinoshita, Koji; Kawai, Makoto; Minai, Kosuke; Ogawa, Kazuo; Inoue, Yasunori; Yoshimura, Michihiro
2016-07-15
Plasma B-type natriuretic peptide (BNP) levels may vary widely among patients with similar stages of heart failure, in whom obesity might be the only factor reducing plasma BNP levels. We investigated the effect of obesity and body mass index (BMI) on plasma BNP levels using serial measurements before and after treatment (pre- and post-BNP and pre- and post-BMI) in patients with acute heart failure. Multiple regression analysis and covariance structure analysis were performed to study the interactions between clinical factors in 372 patients. The pre-BMI was shown as a combination index of obesity and fluid accumulation, whereas the post-BMI was a conventional index of obesity. There was a significant inverse correlation between BMI and BNP in each condition before and after treatment for heart failure. The direct significant associations of the log pre-BNP with the log post-BNP (β: 0.387), the post-BMI (β: -0.043), and the pre-BMI (β: 0.030) were analyzed by using structural equation modeling. The post-BMI was inversely correlated, but importantly, the pre-BMI was positively correlated, with the log pre-BNP, because the pre-BMI probably entailed an element of fluid accumulation. There were few patients with extremely high levels of pre-BNP among those with high post-BMI, due to suppressed secretion of BNP. The low plasma BNP levels in true obesity patients with acute heart failure are of concern, because plasma BNP cannot increase in such patients. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Nekouei, Zohreh Khayyam; Yousefy, Alireza; Doost, Hamid Taher Neshat; Manshaee, Gholamreza; Sadeghei, Masoumeh
2014-01-01
Background: Conducted researches show that psychological factors may have a very important role in the etiology, continuity and consequences of coronary heart diseases. This study has drawn the psychological risk and protective factors and their effects in patients with coronary heart diseases (CHD) in a structural model. It aims to determine the structural relations between psychological risk and protective factors with quality of life in patients with coronary heart disease. Materials and Methods: The present cross-sectional and correlational studies were conducted using structural equation modeling. The study sample included 398 patients of coronary heart disease in the university referral Hospital, as well as other city health care centers in Isfahan city. They were selected based on random sampling method. Then, in case, they were executed the following questionnaires: Coping with stressful situations (CISS- 21), life orientation (LOT-10), general self-efficacy (GSE-10), depression, anxiety and stress (DASS-21), perceived stress (PSS-14), multidimensional social support (MSPSS-12), alexithymia (TAS-20), spiritual intelligence (SQ-23) and quality of life (WHOQOL-26). Results: The results showed that protective and risk factors could affect the quality of life in patients with CHD with factor loadings of 0.35 and −0.60, respectively. Moreover, based on the values of the framework of the model such as relative chi-square (CMIN/DF = 3.25), the Comparative Fit Index (CFI = 0.93), the Parsimony Comparative Fit Index (PCFI = 0.68), the Root Mean Square Error of Approximation (RMSEA = 0.07) and details of the model (significance of the relationships) it has been confirmed that the psychocardiological structural model of the study is the good fitting model. Conclusion: This study was among the first to research the different psychological risk and protective factors of coronary heart diseases in the form of a structural model. The results of this study have emphasized the necessity of noticing the psychological factors in primary prevention by preventive programs and in secondary prevention by rehabilitation centers to improve the quality of life of the people with heart diseases. PMID:24778660
FLUID MECHANICS OF ARTIFICIAL HEART VALVES
Dasi, Lakshmi P; Simon, Helene A; Sucosky, Philippe; Yoganathan, Ajit P
2009-01-01
SUMMARY 1. Artificial heart valves have been in use for over five decades to replace diseased heart valves. Since the first heart valve replacement performed with a caged-ball valve, more than 50 valve designs have been developed, differing principally in valve geometry, number of leaflets and material. To date, all artificial heart valves are plagued with complications associated with haemolysis, coagulation for mechanical heart valves and leaflet tearing for tissue-based valve prosthesis. For mechanical heart valves, these complications are believed to be associated with non-physiological blood flow patterns. 2. In the present review, we provide a bird’s-eye view of fluid mechanics for the major artificial heart valve types and highlight how the engineering approach has shaped this rapidly diversifying area of research. 3. Mechanical heart valve designs have evolved significantly, with the most recent designs providing relatively superior haemodynamics with very low aerodynamic resistance. However, high shearing of blood cells and platelets still pose significant design challenges and patients must undergo life-long anticoagulation therapy. Bioprosthetic or tissue valves do not require anticoagulants due to their distinct similarity to the native valve geometry and haemodynamics, but many of these valves fail structurally within the first 10–15 years of implantation. 4. These shortcomings have directed present and future research in three main directions in attempts to design superior artificial valves: (i) engineering living tissue heart valves; (ii) development of advanced computational tools; and (iii) blood experiments to establish the link between flow and blood damage. PMID:19220329
Fluid mechanics of artificial heart valves.
Dasi, Lakshmi P; Simon, Helene A; Sucosky, Philippe; Yoganathan, Ajit P
2009-02-01
1. Artificial heart valves have been in use for over five decades to replace diseased heart valves. Since the first heart valve replacement performed with a caged-ball valve, more than 50 valve designs have been developed, differing principally in valve geometry, number of leaflets and material. To date, all artificial heart valves are plagued with complications associated with haemolysis, coagulation for mechanical heart valves and leaflet tearing for tissue-based valve prosthesis. For mechanical heart valves, these complications are believed to be associated with non-physiological blood flow patterns. 2. In the present review, we provide a bird's-eye view of fluid mechanics for the major artificial heart valve types and highlight how the engineering approach has shaped this rapidly diversifying area of research. 3. Mechanical heart valve designs have evolved significantly, with the most recent designs providing relatively superior haemodynamics with very low aerodynamic resistance. However, high shearing of blood cells and platelets still pose significant design challenges and patients must undergo life-long anticoagulation therapy. Bioprosthetic or tissue valves do not require anticoagulants due to their distinct similarity to the native valve geometry and haemodynamics, but many of these valves fail structurally within the first 10-15 years of implantation. 4. These shortcomings have directed present and future research in three main directions in attempts to design superior artificial valves: (i) engineering living tissue heart valves; (ii) development of advanced computational tools; and (iii) blood experiments to establish the link between flow and blood damage.
Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances.
Fernández-Falgueras, Anna; Sarquella-Brugada, Georgia; Brugada, Josep; Brugada, Ramon; Campuzano, Oscar
2017-01-29
Sudden cardiac death poses a unique challenge to clinicians because it may be the only symptom of an inherited heart condition. Indeed, inherited heart diseases can cause sudden cardiac death in older and younger individuals. Two groups of familial diseases are responsible for sudden cardiac death: cardiomyopathies (mainly hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) and channelopathies (mainly long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). This review focuses on cardiac channelopathies, which are characterized by lethal arrhythmias in the structurally normal heart, incomplete penetrance, and variable expressivity. Arrhythmias in these diseases result from pathogenic variants in genes encoding cardiac ion channels or associated proteins. Due to a lack of gross structural changes in the heart, channelopathies are often considered as potential causes of death in otherwise unexplained forensic autopsies. The asymptomatic nature of channelopathies is cause for concern in family members who may be carrying genetic risk factors, making the identification of these genetic factors of significant clinical importance.
Wilson, M G; Sharma, S; Carré, F; Charron, P; Richard, P; O'Hanlon, R; Prasad, S K; Heidbuchel, H; Brugada, J; Salah, O; Sheppard, M; George, K P; Whyte, G; Hamilton, B; Chalabi, H
2012-01-01
Preparticipation screening programmes for underlying cardiac pathologies are now commonplace for many international sporting organisations. However, providing medical clearance for an asymptomatic athlete without a family history of sudden cardiac death (SCD) is especially challenging when the athlete demonstrates particularly abnormal repolarisation patterns, highly suggestive of an inherited cardiomyopathy or channelopathy. Deep T-wave inversions of ≥2 contiguous anterior or lateral leads (but not aVR, and III) are of major concern for sports cardiologists who advise referring team physicians, as these ECG alterations are a recognised manifestation of hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Subsequently, inverted T-waves may represent the first and only sign of an inherited heart muscle disease, in the absence of any other features and before structural changes in the heart can be detected. However, to date, there remains little evidence that deep T-wave inversions are always pathognomonic of either a cardiomyopathy or an ion channel disorder in an asymptomatic athlete following long-term follow-up. This paper aims to provide a systematic review of the prevalence of T-wave inversion in athletes and examine T-wave inversion and its relationship to structural heart disease, notably HCM and ARVC with a view to identify young athletes at risk of SCD during sport. Finally, the review proposes clinical management pathways (including genetic testing) for asymptomatic athletes demonstrating significant T-wave inversion with structurally normal hearts. PMID:23097480
Wilson, M G; Sharma, S; Carré, F; Charron, P; Richard, P; O'Hanlon, R; Prasad, S K; Heidbuchel, H; Brugada, J; Salah, O; Sheppard, M; George, K P; Whyte, G; Hamilton, B; Chalabi, H
2012-11-01
Preparticipation screening programmes for underlying cardiac pathologies are now commonplace for many international sporting organisations. However, providing medical clearance for an asymptomatic athlete without a family history of sudden cardiac death (SCD) is especially challenging when the athlete demonstrates particularly abnormal repolarisation patterns, highly suggestive of an inherited cardiomyopathy or channelopathy. Deep T-wave inversions of ≥ 2 contiguous anterior or lateral leads (but not aVR, and III) are of major concern for sports cardiologists who advise referring team physicians, as these ECG alterations are a recognised manifestation of hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Subsequently, inverted T-waves may represent the first and only sign of an inherited heart muscle disease, in the absence of any other features and before structural changes in the heart can be detected. However, to date, there remains little evidence that deep T-wave inversions are always pathognomonic of either a cardiomyopathy or an ion channel disorder in an asymptomatic athlete following long-term follow-up. This paper aims to provide a systematic review of the prevalence of T-wave inversion in athletes and examine T-wave inversion and its relationship to structural heart disease, notably HCM and ARVC with a view to identify young athletes at risk of SCD during sport. Finally, the review proposes clinical management pathways (including genetic testing) for asymptomatic athletes demonstrating significant T-wave inversion with structurally normal hearts.
Malik, Archana; Hellinger, Jeffrey C; Servaes, Sabah; Schwartz, Mathew C; Keller, Marc S; Epelman, Monica
2017-03-01
CT angiography is gaining broader acceptance in the evaluation of children with known or suspected congenital heart disease. These studies include non-cardiovascular structures such as the mediastinum, lung parenchyma and upper abdominal organs. It is important to inspect all these structures for potential abnormalities that might be clinically important and, in some cases, may impact care plans. To determine the prevalence of non-cardiovascular findings in CT angiography of children with congenital heart disease. During 28 months, 300 consecutive children (170 males; mean age: 7.1 years, age range: 6 h-26 years), referred from a tertiary pediatric cardiology center, underwent clinically indicated CT angiography to evaluate known or suspected congenital heart disease. Slightly more than half (n = 169) of the patients were postoperative or post-intervention. Examinations were retrospectively reviewed, and non-cardiovascular findings were recorded and tabulated by organ system, congenital heart disease and operative procedure in conjunction with outcomes from medical charts. Non-cardiovascular findings were identified in 83% (n = 250 / 300) of the studies for a total of 857 findings. In 221 patients (n = 73.7% of 300) a total of 813 non-cardiovascular findings were clinically significant, while in 9.7% (n = 29 / 300) of patients, 5.1% (n = 44 / 857) of the findings were nonsignificant. In 38.3% (n = 115 / 300) of patients with significant non-cardiovascular pathology, the findings were unexpected and directly impacted patient care plans. Commonly involved organs with non-cardiovascular findings were the lungs with 280 non-cardiovascular findings in 176 / 300 (58.7%) of patients, the airway with 139 non-cardiovascular findings in 103 / 300 (34.3%) of patients and the liver with 108 non-cardiovascular findings in 72 / 300 (24.0%) of patients. Syndromic associations were noted in 22% (n = 66 / 300) of the patients. Non-cardiovascular findings are common in children with congenital heart disease who undergo CT angiography. Based upon our study population, if a child with congenital heart disease has a CT angiography, five out of six will have non-cardiovascular findings, while nearly three out of four (73.7%; 221 / 300) will have significant non-cardiovascular findings. Close attention to the non-cardiovascular structures in children with congenital heart disease presenting for a CT angiography is recommended as in nearly 40% of these children, findings were unexpected and directly altered patient care.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.
2006-12-18
Background - The human heart is composed of a helicalnetwork of muscle fibers. These fibers are organized to form sheets thatare separated by cleavage surfaces. This complex structure of fibers andsheets is responsible for the orthotropic mechanical properties ofcardiac muscle. The understanding of the configuration of the 3D fiberand sheet structure is important for modeling the mechanical andelectrical properties of the heart and changes in this configuration maybe of significant importance to understand the remodeling aftermyocardial infarction.Methods - Anisotropic least square filteringfollowed by fiber and sheet tracking techniques were applied to DiffusionTensor Magnetic Resonance Imaging (DTMRI) data of the excisedmore » humanheart. The fiber configuration was visualized by using thin tubes toincrease 3-dimensional visual perception of the complex structure. Thesheet structures were reconstructed from the DTMRI data, obtainingsurfaces that span the wall from the endo- to the epicardium. Allvisualizations were performed using the high-quality ray-tracing softwarePOV-Ray. Results - The fibers are shown to lie in sheets that haveconcave or convex transmural structure which correspond to histologicalstudies published in the literature. The fiber angles varied depending onthe position between the epi- and endocardium. The sheets had a complexstructure that depended on the location within the myocardium. In theapex region the sheets had more curvature. Conclusions - A high-qualityvisualization algorithm applied to demonstrated high quality DTMRI datais able to elicit the comprehension of the complex 3 dimensionalstructure of the fibers and sheets in the heart.« less
Castonguay, Alexandre; Lefebvre, Joël; Pouliot, Philippe; Avti, Pramod; Moeini, Mohammad; Lesage, Frédéric
2017-01-01
Normal aging is accompanied by structural changes in the heart architecture. To explore this remodeling, we used a serial optical coherence tomography scanner to image entire mouse hearts at micron scale resolution. Ex vivo hearts of 7 young (4 months) and 5 old (24 months) C57BL/6 mice were acquired with the imaging platform. OCT of the myocardium revealed myofiber orientation changing linearly from the endocardium to the epicardium. In old mice, this rate of change was lower when compared to young mice while the average volume of old mice hearts was significantly larger (p<0.05). Myocardial wall thickening was also accompanied by extracellular spacing in the endocardium, resulting in a lower OCT attenuation coefficient in old mice endocardium (p<0.05). Prior to serial sectioning, cardiac function of the same hearts was imaged in vivo using MRI and revealed a reduced ejection fraction with aging. The use of a serial optical coherence tomography scanner allows new insight into fine age-related changes of the heart associated with changes in heart function. PMID:29188099
Hemodynamic adaptation to suboptimal fetal growth in patients with single ventricle physiology.
Alsaied, Tarek; Tseng, Stephanie; King, Eileen; Hahn, Eunice; Divanovic, Allison; Habli, Mounira; Cnota, James
2018-06-10
In fetuses with structurally normal heart and suboptimal fetal growth (SFG), umbilical artery vascular resistance increases as measured by umbilical artery pulsatility index (UA-PI). The objective of this study is to compare hemodynamic responses to SFG in fetuses with single ventricle (SV) and controls with structurally normal heart. Fetal echocardiograms around 30 weeks of gestation were reviewed. UA-PI and middle cerebral artery pulsatility index (MCA-PI) were calculated. SFG was defined as a birth weight below 25th percentile for gestational age. Studies from 92 fetuses were reviewed-SV (n = 50) and controls (n = 42). The prevalence of SFG was higher in SV compared to controls (46% vs 21%, P = .02). In patients with normal heart and SFG, UAPI was significantly higher than normal controls (P = .003) suggesting increased placental vascular resistance. In SV with SFG there was no difference in UAPI compared to SV without SFG. There was no difference in MCA-PI between the groups. The hemodynamic response to SFG in SV varies from fetuses with structurally normal heart. The mechanism of SFG and the placental pathology may be distinct in SV. © 2018 Wiley Periodicals, Inc.
Ruan, Guoran; Ren, Haojin; Zhang, Chi; Zhu, Xiaogang; Xu, Chao; Wang, Liyue
2018-01-01
QiShenYiQi dripping pills (QSYQ), a traditional Chinese medicine, are commonly used to treat coronary heart disease, and QSYQ was recently approved as a complementary treatment for ischemic heart failure in China. However, only few studies reported on whether QSYQ exerts a protective effect on heart failure induced by pressure overload. In this study, we explored the role of QSYQ in a mouse model of heart failure induced by transverse aortic constriction (TAC). Twenty-eight C57BL/6J mice were divided into four groups: Sham + NS group, Sham + QSYQ group, TAC + NS group, and TAC + QSYQ group. QSYQ dissolved in normal saline (NS) was administered intragastrically (3.5 mg/100 g/day) in the Sham + QSYQ and TAC + QSYQ groups. In the Sham + NS and TAC + NS groups, NS was provided every day intragastrically. Eight weeks after TAC, echocardiography, and cardiac catheterization were performed to evaluate the cardiac function, and immunofluorescent staining with anti-actinin2 antibody was performed to determine the structure of the myocardial fibers. Moreover, TUNEL staining and Masson trichrome staining were employed to assess the effects of QSYQ on cardiac apoptosis and cardiac fibrosis. Western blots and real-time polymerase chain reaction (PCR) were used to measure the expression levels of vascular endothelial growth factor (VEGF) in the heart, and immunohistochemical staining with anti-CD31 antibody was performed to explore the role of QSYQ in cardiac angiogenesis. Results showed that TAC-induced cardiac dysfunction and disrupted structure of myocardial fibers significantly improved after QSYQ treatment. Moreover, QSYQ treatment also significantly improved cardiac apoptosis and cardiac fibrosis in TAC-induced heart failure, which was accompanied by an increase in VEGF expression levels and maintenance of microvessel density in the heart. In conclusion, QSYQ exerts a protective effect on TAC-induced heart failure, which could be attributed to enhanced cardiac angiogenesis, which is closely related to QSYQ. Thus, QSYQ may be a promising traditional Chinese medicine for the treatment of heart failure induced by pressure overload such as hypertension.
ACE phenotyping in human heart
Tikhomirova, Victoria E.; Kost, Olga A.; Kryukova, Olga V.; Golukhova, Elena Z.; Bulaeva, Naida I.; Zholbaeva, Aigerim Z.; Bokeria, Leo A.; Garcia, Joe G. N.
2017-01-01
Aims Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. Methods and results We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10–15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. “Conformational fingerprint” of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Conclusions Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk. PMID:28771512
Diabetic Cardiomyopathy and Metabolic Remodeling of the Heart
Battiprolu, Pavan K.; Lopez-Crisosto, Camila; Wang, Zhao V.; Nemchenko, Andriy; Lavandero, Sergio; Hill, Joseph A.
2012-01-01
The incidence and prevalence of diabetes mellitus are each increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. However, the diabetic milieu is itself intrinsically noxious to the heart, and cardiomyopathy can develop independent of elevated blood pressure or coronary artery disease. This process, termed diabetic cardiomyopathy, is characterized by significant changes in the physiology, structure, and mechanical function of the heart. Presently, therapy for patients with diabetes focuses largely on glucose control, and attention to the heart commences with the onset of symptoms. When the latter develops, standard therapy for heart failure is applied. However, recent studies highlight that specific elements of the pathogenesis of diabetic heart disease are unique, raising the prospect of diabetes-specific therapeutic intervention. Here, we review recently unveiled insights into the pathogenesis of diabetic cardiomyopathy and associated metabolic remodeling with an eye toward identifying novel targets with therapeutic potential. PMID:23123443
The incidence of chromosome abnormalities in neonates with structural heart disease.
Dykes, John C; Al-mousily, Mohammad F; Abuchaibe, Eda-Cristina; Silva, Jennifer N; Zadinsky, Jennifer; Duarte, Daniel; Welch, Elizabeth
2016-04-01
This study was conducted to determine the prevalence of chromosomal anomalies in newborns with structural heart disease admitted to the cardiac intensive care unit (CICU) at Nicklaus Children's Hospital (NCH). A retrospective review identified newborns age 30 days or less admitted to NCH CICU between 2004 and 2010. Patients with structural heart disease who required admission to our CICU and received karyotype or karyotype and fluorescent in situ hybridization (FISH) testing were included in the study. All patients were examined for the presence of dysmorphic features. Four hundred and eighty-two patients met the criteria for the study; 405 (84%) received both karyotype and FISH. Chromosome abnormalities were present in 86 (17.8%) patients. Syndromes accounted for 20 (5.1%) of those with normal chromosomes. Dysmorphic features were seen in 79.1% of patients with abnormal chromosomes and 25.5% of those with normal chromosomes. All patients with syndromes were dysmorphic. Race and gender did not significantly affect the incidence of genetic abnormalities. Chromosome abnormalities, including syndromes, are prevalent in newborns with congenital heart disease. Further research is needed to evaluate the utility of cytogenetic screening in all children with congenital heart disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Cardiac structural changes and electrical remodeling in a thiamine-deficiency model in rats.
Roman-Campos, D; Campos, A C; Gioda, C R; Campos, P P; Medeiros, M A A; Cruz, J S
2009-06-05
Thiamine is an important cofactor present in many biochemical reactions, and its deprivation can lead to heart dysfunction. Little is known about the influence of thiamine deprivation on the electrophysiological behavior of the isolated heart cells and information about thiamine deficiency in heart morphology is controversial. Thus, we decided to investigate the major repolarizing conductances and their influence in the action potential (AP) waveform as well as the changes in the heart structure in a set of thiamine deficiency in rats. Using the patch-clamp technique, we investigated inward (I(K1)) and outward K(+) currents (I(to)), T-type and L-type Ca(2+) currents and APs. To evaluate heart morphology we used hematoxylin and eosin in transversal heart sections. Thiamine deficiency caused a marked decrease in left ventricle thickness, cardiomyocyte number, cell length and width, and membrane capacitance. When evaluating I(to) we did not find difference in current amplitude; however an acceleration of I(to) inactivation was observed. I(K1) showed a reduction in the amplitude and slope conductance, which implicated a less negative resting membrane potential in cardiac myocytes isolated from thiamine-deficient rats. We did not find any difference in L-type Ca(2+) current density. T-type Ca(2+) current was not observed. In addition, we did not observe significant changes in AP repolarization. Based on our study we can conclude that thiamine deficiency causes heart hypotrophy and not heart hypertrophy. Moreover, we provided evidence that there is no major electrical remodeling during thiamine deficiency, a feature of heart failure models.
Exercises in anatomy: the normal heart.
Anderson, Robert H; Sarwark, Anne; Spicer, Diane E; Backer, Carl L
2014-01-01
In this series of videoclips, we analyze the anatomy of the normal heart. We begin our overview by emphasizing the need, in the current era, to describe the heart in attitudinally appropriate fashion. Increasingly, clinicians are demonstrating the features of the heart as it is located within the body. It is no longer satisfactory, therefore, to describe these components in a ‘Valentine’ fashion, as continues to be the case in most textbooks of normal or cardiac anatomy. We then emphasize the importance of the so-called morphological method, which states that structures within the heart should be defined on the basis of their own intrinsic morphology, and not according to other parts, which are themselves variable. We continue by using this concept to show how the appendages serve to distinguish between the atrial chambers, while the apical trabecular components provide the features to distinguish the ventricles. We then return to the cardiac chambers, emphasizing features of surgical significance, in particular the locations of the cardiac conduction tissues. We proceed by examining the cardiac valves, and conclude by providing a detailed analysis of the septal structures. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Manipulation of sarcoplasmic reticulum Ca2+ release in heart failure through mechanical intervention
Ibrahim, Michael; Nader, Anas; Yacoub, Magdi H; Terracciano, Cesare
2015-01-01
Left ventricular assist devices (LVADs) were developed as a means of temporary circulatory support, but the mechanical unloading they offer also results in significant reverse remodelling. In selected patients, these improvements are sufficient to allow ultimate device explantation without requiring transplantation; this represents a fundamental shift in our understanding of heart failure. Like heart failure itself, LVADs influence multiple biological systems. The transverse tubules are a system of membrane invaginations in ventricular cardiomyocytes which allow rapid propagation of the action potential throughout the cell. Through their dense concentration of L-type Ca2+ channels in close proximity to intracellular ryanodine receptors, the t-tubules enable synchronous Ca2+ release throughout the cell. The t-tubules’ structure appears to be specifically regulated by mechanical load, such that either the overload of heart failure (or the spontaneously hypertensive rat model) or the profound unloading in a chronically unloaded heart result in impaired t-tubule structure, with ineffective Ca2+ release. While there are multiple molecular pathways which underpin t-tubule regulation, Telethonin (Tcap) appears to be important in regulating the effect of altered loading on the t-tubule system. PMID:25922157
Smith predictor-based robot control for ultrasound-guided teleoperated beating-heart surgery.
Bowthorpe, Meaghan; Tavakoli, Mahdi; Becher, Harald; Howe, Robert
2014-01-01
Performing surgery on fast-moving heart structures while the heart is freely beating is next to impossible. Nevertheless, the ability to do this would greatly benefit patients. By controlling a teleoperated robot to continuously follow the heart's motion, the heart can be made to appear stationary. The surgeon will then be able to operate on a seemingly stationary heart when in reality it is freely beating. The heart's motion is measured from ultrasound images and thus involves a non-negligible delay due to image acquisition and processing, estimated to be 150 ms that, if not compensated for, can cause the teleoperated robot's end-effector (i.e., the surgical tool) to collide with and puncture the heart. This research proposes the use of a Smith predictor to compensate for this time delay in calculating the reference position for the teleoperated robot. The results suggest that heart motion tracking is improved as the introduction of the Smith predictor significantly decreases the mean absolute error, which is the error in making the distance between the robot's end-effector and the heart follow the surgeon's motion, and the mean integrated square error.
Nakahara, Takehiro; Jinzaki, Masahiro; Niwamae, Nogiku; Saito, Yuuichirou; Arai, Masashi; Tsushima, Yoshito; Kuribayashi, Sachio; Kurabayashi, Masahiko
2014-01-01
Despite the improvement of cardiac CT, right heart visualization remains challenging. We herein describe a new method, called the time-adjusted gradual replacement injection protocol. The aim of this study was to compare this protocol with the split-bolus injection protocol. Fifty-two patients who had undergone dual-source cardiac CT were retrospectively recruited. Twenty-six patients were injected by using the split-bolus injection protocol, and 26 patients were injected by using the time-adjusted gradual replacement injection protocol. For this method, we injected contrast medium for 10 seconds at a flow rate of 0.07 × body weight mL/s, then gradually replaced the contrast material with saline until 2 seconds before finishing the scans. The CT attenuation was measured in 4 chambers, the aorta, and the coronary arteries. The visualization of the anatomic structures and the occurrence and severity of streak artifacts were scored for the cardiac structures in the heart. For the analyses, either Welch t-test or Student t-test was performed. In the right heart, the CT values and visualization scores were significantly higher in the time-adjusted replacement injection group than in the split-bolus injection group, whereas the artifact scores were comparable between the 2 groups. The CT values, visualization scores, and artifact scores of the left heart were not significantly different between the 2 groups. In this study, the time-adjusted gradual replacement injection protocol provided excellent attenuation for visualization of the right heart. This method may help to accurately evaluate the right cardiac anatomy and thereby identify any potential diseases. Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.
Ramaswamy, Prema; Rafii, Daniela; Osmolovsky, Marina; Agarwal, Arpit; Amirtharaj, Cynthia
2016-12-01
Evidence suggests an association between left heart obstructive lesions and dilated coronary sinus (DCS), but this has not been studied in fetuses. A retrospective review of fetal echocardiograms (FE) over an 8-year period was conducted, and patients with DCS were identified and confirmed postnatally. There were 5840 FE performed on 4920 women during this period. Of 49 patients with DCS, 22 had normal intracardiac anatomy and 27 patients had congenital heart disease (CHD) yielding an incidence of 4.6 % in the presence of CHD (27/584). Of 27 patients with DCS and CHD, approximately a third had either hypoplastic left ventricles and/or coarctations (10/27, 37 %). The incidence of left heart obstructive lesions was much higher in the presence of a DCS (37 % vs 45/557, 8 %, p < 0.0001). The odds ratio of left heart hypoplasia in fetuses with CHD and a DCS was 6.6 (95 % CI 2.8-15.3). Comparison of patients with postnatally confirmed coarctation with those with normal intracardiac anatomy with DCS, revealed that in the former, the right ventricle (p = 0.005), pulmonic valve annulus (p = 0.0001) and the tricuspid inflow were larger (p = 0.001) compared to corresponding left-sided structures. The size of the DCS was not significantly different between the two groups, but in the former, the DCS was more closely related to the posterior leaflet of the mitral valve and caused a significant diminution of the mitral inflow. Our study suggests a strong association, possibly causal, between left heart obstructive lesions and DCS in utero.
Downregulation in GATA4 and Downstream Structural and Contractile Genes in the db/db Mouse Heart
Broderick, Tom L.; Jankowski, Marek; Wang, Donghao; Danalache, Bogdan A.; Parrott, Cassandra R.; Gutkowska, Jolanta
2012-01-01
Reduced expression of GATA4, a transcriptional factor for structural and cardioprotective genes, has been proposed as a factor contributing to the development of cardiomyopathy. We investigated whether the reduction of cardiac GATA4 expression reported in diabetes alters the expression of downstream genes, namely, atrial natriuretic peptide (ANP), B-type natriuretic, peptide (BNP), and α- and β-myosin heavy chain (MHC). db/db mice, a model of type 2 diabetes, with lean littermates serving as controls, were studied. db/db mice exhibited obesity, hyperglycemia, and reduced protein expression of cardiac GLUT4 and IRAP (insulin-regulated aminopeptidase), the structural protein cosecreted with GLUT4. Hearts from db/db mice had reduced protein expression of GATA4 (~35%) with accompanying reductions in mRNA expression of ANP (~40%), BNP (~85%), and α-MHC mRNA (~50%) whereas expression of β-MHC mRNA was increased by ~60%. Low GATA4 was not explained by an increased ligase or atrogin1 expression. CHIP protein content was modestly downregulated (27%) in db/db mice whereas mRNA and protein expression of the CHIP cochaperone HSP70 was significantly decreased in db/db hearts. Our results indicate that low GATA4 in db/db mouse heart is accompanied by reduced expression of GATA4-regulated cardioprotective and structural genes, which may explain the development of cardiomyopathy in diabetes. PMID:22474596
An easy-to-use technique to characterize cardiodynamics from first-return maps on ΔRR-intervals
NASA Astrophysics Data System (ADS)
Fresnel, Emeline; Yacoub, Emad; Freitas, Ubiratan; Kerfourn, Adrien; Messager, Valérie; Mallet, Eric; Muir, Jean-François; Letellier, Christophe
2015-08-01
Heart rate variability analysis using 24-h Holter monitoring is frequently performed to assess the cardiovascular status of a patient. The present retrospective study is based on the beat-to-beat interval variations or ΔRR, which offer a better view of the underlying structures governing the cardiodynamics than the common RR-intervals. By investigating data for three groups of adults (with normal sinus rhythm, congestive heart failure, and atrial fibrillation, respectively), we showed that the first-return maps built on ΔRR can be classified according to three structures: (i) a moderate central disk, (ii) a reduced central disk with well-defined segments, and (iii) a large triangular shape. These three very different structures can be distinguished by computing a Shannon entropy based on a symbolic dynamics and an asymmetry coefficient, here introduced to quantify the balance between accelerations and decelerations in the cardiac rhythm. The probability P111111 of successive heart beats without large beat-to-beat fluctuations allows to assess the regularity of the cardiodynamics. A characteristic time scale, corresponding to the partition inducing the largest Shannon entropy, was also introduced to quantify the ability of the heart to modulate its rhythm: it was significantly different for the three structures of first-return maps. A blind validation was performed to validate the technique.
Fractal Based Analysis of the Influence of Odorants on Heart Activity
NASA Astrophysics Data System (ADS)
Namazi, Hamidreza; Kulish, Vladimir V.
2016-12-01
An important challenge in heart research is to make the relation between the features of external stimuli and heart activity. Olfactory stimulation is an important type of stimulation that affects the heart activity, which is mapped on Electrocardiogram (ECG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the ECG signal. This study investigates the relation between the structures of heart rate and the olfactory stimulus (odorant). We show that the complexity of the heart rate is coupled with the molecular complexity of the odorant, where more structurally complex odorant causes less fractal heart rate. Also, odorant having higher entropy causes the heart rate having lower approximate entropy. The method discussed here can be applied and investigated in case of patients with heart diseases as the rehabilitation purpose.
The human heart: application of the golden ratio and angle.
Henein, Michael Y; Zhao, Ying; Nicoll, Rachel; Sun, Lin; Khir, Ashraf W; Franklin, Karl; Lindqvist, Per
2011-08-04
The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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
Evidence-based medicine and patient choice: the case of heart failure care.
Sanders, Tom; Harrison, Stephen; Checkland, Kath
2008-04-01
The implementation of evidence-based medicine and policies aimed at increasing user involvement in health care decisions are central planks of contemporary English health policy. Yet they are potentially in conflict. Our aim was to explore how clinicians working in the field of heart failure resolve this conflict. Qualitative semi-structured interviews were carried out with health professionals who were currently caring for patients with heart failure, and observations were conducted at one dedicated heart failure clinic in northern England. While clinicians acknowledged that patients' ideas and preferences should be an important part of treatment decisions, the widespread acceptance of an evidence-based clinical protocol for heart failure among the clinic doctors significantly influenced the content and style of the consultation. Evidence-based medicine was used to buttress professional authority and seemed to provide an additional barrier to the adoption of patient-centred clinical practice.
Cardiac torsion and electromagnetic fields: the cardiac bioinformation hypothesis.
Burleson, Katharine O; Schwartz, Gary E
2005-01-01
Although in physiology the heart is often referred to as a simple piston pump, there are in fact two additional features that are integral to cardiac physiology and function. First, the heart as it contracts in systole, also rotates and produces torsion due to the structure of the myocardium. Second, the heart produces a significant electromagnetic field with each contraction due to the coordinated depolarization of myocytes producing a current flow. Unlike the electrocardiogram, the magnetic field is not limited to volume conduction and extends outside the body. The therapeutic potential for interaction of this cardioelectromagnetic field both within and outside the body is largely unexplored. It is our hypothesis that the heart functions as a generator of bioinformation that is central to normative functioning of body. The source of this bioinformation is based on: (1) vortex blood flow in the left ventricle; (2) a cardiac electromagnetic field and both; (3) heart sounds; and (4) pulse pressure which produce frequency and amplitude information. Thus, there is a multidimensional role for the heart in physiology and biopsychosocial dynamics. Recognition of these cardiac properties may result in significant implications for new therapies for cardiovascular disease based on increasing cardiac energy efficiency (coherence) and bioinformation from the cardioelectromagnetic field. Research studies to test this hypothesis are suggested.
Cardiac damage in athlete's heart: When the "supernormal" heart fails!
Carbone, Andreina; D'Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele
2017-06-26
Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.
Cardiac damage in athlete’s heart: When the “supernormal” heart fails!
Carbone, Andreina; D’Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele
2017-01-01
Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete’s blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete’s heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded. PMID:28706583
Chambers, John; Kabir, Saleha; Cajeat, Eric
2014-01-01
Background Heart disease is difficult to detect clinically and it has been suggested that echocardiography should be available to all patients with possible cardiac symptoms or signs. Aim To analyse the results of 2 years of open access echocardiography for the frequency of structural heart disease according to request. Design and setting Retrospective database analysis in a teaching hospital open access echocardiography service. Method Reports of all open access transthoracic echocardiograms between January 2011 and December 2012 were categorised as normal, having minor abnormalities, or significant abnormalities according to the indication. Results There were 2343 open access echocardiograms performed and there were significant abnormalities in 29%, predominantly valve disease (n = 304, 13%), LV systolic dysfunction (n = 179, 8%), aortic dilatation (n = 80, 3%), or pulmonary hypertension (n = 91, 4%). If echocardiography had been targeted at a high-risk group, 267 with valve disease would have been detected (compared to 127 with murmur alone) and 139 with LV systolic dysfunction (compared to 91 with suspected heart failure alone). Most GP practices requested fewer than 10 studies, but 6 practices requested over 70 studies. Conclusion Open access echocardiograms are often abnormal but structural disease may not be suspected from the clinical request. Uptake by individual practices is patchy. A targeted expansion of echocardiography in patients with a high likelihood of disease is therefore likely to increase the detection of clinically important pathology. PMID:24567615
Chambers, John; Kabir, Saleha; Cajeat, Eric
2014-02-01
Heart disease is difficult to detect clinically and it has been suggested that echocardiography should be available to all patients with possible cardiac symptoms or signs. To analyse the results of 2 years of open access echocardiography for the frequency of structural heart disease according to request. Retrospective database analysis in a teaching hospital open access echocardiography service. Reports of all open access transthoracic echocardiograms between January 2011 and December 2012 were categorised as normal, having minor abnormalities, or significant abnormalities according to the indication. There were 2343 open access echocardiograms performed and there were significant abnormalities in 29%, predominantly valve disease (n = 304, 13%), LV systolic dysfunction (n = 179, 8%), aortic dilatation (n = 80, 3%), or pulmonary hypertension (n = 91, 4%). If echocardiography had been targeted at a high-risk group, 267 with valve disease would have been detected (compared to 127 with murmur alone) and 139 with LV systolic dysfunction (compared to 91 with suspected heart failure alone). Most GP practices requested fewer than 10 studies, but 6 practices requested over 70 studies. Open access echocardiograms are often abnormal but structural disease may not be suspected from the clinical request. Uptake by individual practices is patchy. A targeted expansion of echocardiography in patients with a high likelihood of disease is therefore likely to increase the detection of clinically important pathology.
Intact Imaging of Human Heart Structure Using X-ray Phase-Contrast Tomography.
Kaneko, Yukihiro; Shinohara, Gen; Hoshino, Masato; Morishita, Hiroyuki; Morita, Kiyozo; Oshima, Yoshihiro; Takahashi, Masashi; Yagi, Naoto; Okita, Yutaka; Tsukube, Takuro
2017-02-01
Structural examination of human heart specimens at the microscopic level is a prerequisite for understanding congenital heart diseases. It is desirable not to destroy or alter the properties of such specimens because of their scarcity. However, many of the currently available imaging techniques either destroy the specimen through sectioning or alter the chemical and mechanical properties of the specimen through staining and contrast agent injection. As a result, subsequent studies may not be possible. X-ray phase-contrast tomography is an imaging modality for biological soft tissues that does not destroy or alter the properties of the specimen. The feasibility of X-ray phase-contrast tomography for the structural examination of heart specimens was tested using infantile and fetal heart specimens without congenital diseases. X-ray phase-contrast tomography was carried out at the SPring-8 synchrotron radiation facility using the Talbot grating interferometer at the bending magnet beamline BL20B2 to visualize the structure of five non-pretreated whole heart specimens obtained by autopsy. High-resolution, three-dimensional images were obtained for all specimens. The images clearly showed the myocardial structure, coronary vessels, and conduction bundle. X-ray phase-contrast tomography allows high-resolution, three-dimensional imaging of human heart specimens. Intact imaging using X-ray phase-contrast tomography can contribute to further structural investigation of heart specimens with congenital heart diseases.
Ischemic preconditioning enhances integrity of coronary endothelial tight junctions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Zhao; Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu
2012-08-31
Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiacmore » TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.« less
Yang, Chao; Xu, Honglai; Cai, Lanjun; Du, Xiaoxiao; Jiang, Yinan; Zhang, Yong; Zhou, Hongmin; Chen, Zhonghua Klaus
2016-05-01
Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy metabolism and has been shown to be protective in ischaemia/reperfusion injury (IRI). We hypothesized that preactivation of AMPK with an activator before donor heart procurement could protect heart grafts from cold IRI. Donor Sprague-Dawley rats were injected intravenously with AMPK activator 5-amino-imidazole-4-carboxamide ribonucleotide (AICAR) or vehicle 30 min before heart procurement. Heart grafts were then preserved in histidine-tryptophan-ketoglutarate (HTK) solution at 4°C for 8 h. After preservation, grafts were immediately mounted on the Langendorff perfusion system and perfused with Krebs-Henseleit buffer at 37°C for 1 h. Adenosine triphosphate (ATP) and malondialdehyde (MDA) content in graft tissue were quantified post-preservation and post-reperfusion. After reperfusion, isolated heart function was assessed using a pressure transducer; cumulative release of creatine kinase (CK) and lactate dehydrogenase (LDH) into the perfusate was measured to assess cardiomyocyte necrosis; ultrastructural changes in the mitochondria of the grafts were examined using transmission electron microscopy (TEM). After preservation, myocardial ATP content in the pretreated hearts was significantly higher than in the control hearts (3.247 ± 0.3034 vs 1.817 ± 0.2533 µmol/g protein; P < 0.05). AICAR-pretreated heart grafts exhibited significantly higher coronary flow (9.667 ± 0.3159 vs 8.033 ± 0.2459 ml/min; P < 0.05) and left ventricular developing pressure (58.67 ± 2.894 vs 42.67 ± 3.333 mmHg; P < 0.05) than the vehicle treated after reperfusion. Cumulative release of CK (300.0 ± 25.30 vs 431.7 ± 42.39 U/l; P < 0.05) and LDH (228.0 ± 16.68 vs 366.8 ± 57.41 U/l; P < 0.05) in the perfusate was significantly lower in the AICAR-pretreated group than that in the control group. Myocardial MDA content was also reduced in the pretreated group (0.5167 ± 0.1046 vs 0.9333 ± 0.1333 nmol/mg protein; P < 0.05). TEM suggested that the mitochondrial structure of AICAR-pretreated hearts was much better preserved. Moreover, AICAR-pretreated hearts significantly diminished cytosolic cytochrome c release after reperfusion. This study demonstrates that pretreatment with AMPK activator AICAR significantly protects heart grafts from extended cold IRI. This novel protocol may be useful and feasible in clinical heart transplantation. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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.
Perrichon, Prescilla; Grosell, Martin; Burggren, Warren W.
2017-01-01
Understanding cardiac function in developing larval fishes is crucial for assessing their physiological condition and overall health. Cardiac output measurements in transparent fish larvae and other vertebrates have long been made by analyzing videos of the beating heart, and modeling this structure using a conventional simple prolate spheroid shape model. However, the larval fish heart changes shape during early development and subsequent maturation, but no consideration has been made of the effect of different heart geometries on cardiac output estimation. The present study assessed the validity of three different heart models (the “standard” prolate spheroid model as well as a cylinder and cone tip + cylinder model) applied to digital images of complete cardiac cycles in larval mahi-mahi and red drum. The inherent error of each model was determined to allow for more precise calculation of stroke volume and cardiac output. The conventional prolate spheroid and cone tip + cylinder models yielded significantly different stroke volume values at 56 hpf in red drum and from 56 to 104 hpf in mahi. End-diastolic and stroke volumes modeled by just a simple cylinder shape were 30–50% higher compared to the conventional prolate spheroid. However, when these values of stroke volume multiplied by heart rate to calculate cardiac output, no significant differences between models emerged because of considerable variability in heart rate. Essentially, the conventional prolate spheroid shape model provides the simplest measurement with lowest variability of stroke volume and cardiac output. However, assessment of heart function—especially if stroke volume is the focus of the study—should consider larval heart shape, with different models being applied on a species-by-species and developmental stage-by-stage basis for best estimation of cardiac output. PMID:28725199
Folliculin (Flcn) inactivation leads to murine cardiac hypertrophy through mTORC1 deregulation
Hasumi, Yukiko; Baba, Masaya; Hasumi, Hisashi; Huang, Ying; Lang, Martin; Reindorf, Rachel; Oh, Hyoung-bin; Sciarretta, Sebastiano; Nagashima, Kunio; Haines, Diana C.; Schneider, Michael D.; Adelstein, Robert S.; Schmidt, Laura S.; Sadoshima, Junichi; Marston Linehan, W.
2014-01-01
Cardiac hypertrophy, an adaptive process that responds to increased wall stress, is characterized by the enlargement of cardiomyocytes and structural remodeling. It is stimulated by various growth signals, of which the mTORC1 pathway is a well-recognized source. Here, we show that loss of Flcn, a novel AMPK–mTOR interacting molecule, causes severe cardiac hypertrophy with deregulated energy homeostasis leading to dilated cardiomyopathy in mice. We found that mTORC1 activity was upregulated in Flcn-deficient hearts, and that rapamycin treatment significantly reduced heart mass and ameliorated cardiac dysfunction. Phospho-AMP-activated protein kinase (AMPK)-alpha (T172) was reduced in Flcn-deficient hearts and nonresponsive to various stimulations including metformin and AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide). ATP levels were elevated and mitochondrial function was increased in Flcn-deficient hearts, suggesting that excess energy resulting from up-regulated mitochondrial metabolism under Flcn deficiency might attenuate AMPK activation. Expression of Ppargc1a, a central molecule for mitochondrial metabolism, was increased in Flcn-deficient hearts and indeed, inactivation of Ppargc1a in Flcn-deficient hearts significantly reduced heart mass and prolonged survival. Ppargc1a inactivation restored phospho-AMPK-alpha levels and suppressed mTORC1 activity in Flcn-deficient hearts, suggesting that up-regulated Ppargc1a confers increased mitochondrial metabolism and excess energy, leading to inactivation of AMPK and activation of mTORC1. Rapamycin treatment did not affect the heart size of Flcn/Ppargc1a doubly inactivated hearts, further supporting the idea that Ppargc1a is the critical element leading to deregulation of the AMPK–mTOR-axis and resulting in cardiac hypertrophy under Flcn deficiency. These data support an important role for Flcn in cardiac homeostasis in the murine model. PMID:24908670
Exercise and the right ventricle: a potential Achilles' heel.
La Gerche, Andre; Rakhit, Dhrubo J; Claessen, Guido
2017-10-01
Exercise is associated with unequivocal health benefits and results in many structural and functional changes of the myocardium that enhance performance and prevent heart failure. However, intense exercise also presents a significant hemodynamic challenge in which the right-sided heart chambers are exposed to a disproportionate increase in afterload and wall stress that can manifest as myocardial fatigue or even damage if intense exercise is sustained for prolonged periods. This review focuses on the physiological factors that result in a disproportionate load on the right ventricle during exercise and the long-term consequences. The changes in cardiac structure and function that define 'athlete's heart' disproportionately affect the right-sided heart chambers and this can raise important diagnostic overlap with some cardiac pathologies, particularly some inherited cardiomyopathies. The interaction between exercise and arrhythmogenic right ventricular cardiomyopathy (ARVC) will be highlighted as an important example of how hemodynamic stressors can combine with deficiencies in cardiac structural elements to cause cardiac dysfunction predisposing to arrhythmias. The extent to which extreme exercise can cause adverse remodelling in the absence of a genetic predisposition remains controversial. In the athlete with profound changes in heart structure, it can be extremely challenging to determine whether common symptoms such as palpitations may be a marker of more sinister arrhythmias. This review discusses some of the techniques that have recently been proposed to identify pathology in these circumstances. Finally, we will discuss recent evidence defining the role of exercise restriction as a therapeutic intervention in individuals predisposed to arrhythmogenic cardiomyopathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
Gerson, Cindy J; Goldstein, Steven; Heacox, Albert E
2009-10-01
Cryopreservation is commonly used for the long-term storage of heart valve allografts. Despite the excellent hemodynamic performance and durability of cryopreserved allografts, reports have questioned whether cryopreservation affects the valvular structural proteins, collagen and elastin. This study uses two-photon laser scanning confocal microscopy (LSCM) to evaluate the effect of cryopreservation on collagen and elastin integrity within the leaflet and conduit of aortic and pulmonary human heart valves. To permit pairwise comparisons of fresh and cryopreserved tissue, test valves were bisected longitudinally with one segment imaged fresh and the other imaged after cryopreservation and brief storage in liquid nitrogen. Collagen was detected by second harmonic generation (SHG) stimulation and elastin by autofluorescence excitation. Qualitative analysis of all resultant images indicated the maintenance of collagen and elastin structure within leaflet and conduit post-cryopreservation. Analysis of the optimized percent laser transmission (OPLT) required for full dynamic range imaging of collagen and elastin showed that OPLT observations were highly variable among both fresh and cryopreserved samples. Changes in donor-specific average OPLT in response to cryopreservation exhibited no consistent directional trend. The donor-aggregated results predominantly showed no statistically significant change in collagen and elastin average OPLT due to cryopreservation. Since OPLT has an inverse relationship with structural signal intensity, these results indicate that there was largely no statistical difference in collagen and elastin signal strength between fresh and cryopreserved tissue. Overall, this study indicates that the conventional cryopreservation of human heart valve allografts does not detrimentally affect their collagen and elastin structural integrity.
SPECT and PET in ischemic heart failure.
Angelidis, George; Giamouzis, Gregory; Karagiannis, Georgios; Butler, Javed; Tsougos, Ioannis; Valotassiou, Varvara; Giannakoulas, George; Dimakopoulos, Nikolaos; Xanthopoulos, Andrew; Skoularigis, John; Triposkiadis, Filippos; Georgoulias, Panagiotis
2017-03-01
Heart failure is a common clinical syndrome associated with significant morbidity and mortality worldwide. Ischemic heart disease is the leading cause of heart failure, at least in the industrialized countries. Proper diagnosis of the syndrome and management of patients with heart failure require anatomical and functional information obtained through various imaging modalities. Nuclear cardiology techniques play a main role in the evaluation of heart failure. Myocardial single photon emission computed tomography (SPECT) with thallium-201 or technetium-99 m labelled tracers offer valuable data regarding ventricular function, myocardial perfusion, viability, and intraventricular synchronism. Moreover, positron emission tomography (PET) permits accurate evaluation of myocardial perfusion, metabolism, and viability, providing high-quality images and the ability of quantitative analysis. As these imaging techniques assess different parameters of cardiac structure and function, variations of sensitivity and specificity have been reported among them. In addition, the role of SPECT and PET guided therapy remains controversial. In this comprehensive review, we address these controversies and report the advances in patient's investigation with SPECT and PET in ischemic heart failure. Furthermore, we present the innovations in technology that are expected to strengthen the role of nuclear cardiology modalities in the investigation of heart failure.
Ojha, Shreesh; Bharti, Saurabh; Golechha, Mahaveer; Sharma, Ashok K; Rani, Neha; Kumari, Santosh; Arya, Dharamvir Singh
2012-01-01
Present study evaluated the cardioprotective effect of Andrographis paniculata (100, 200 or 400 mg/kg) against isoproterenol (85 mg/kg, b.w.)-induced cardiotoxicity referred as myocardial infarction in rats. Isoproterenol significantly (p < 0.05) decreased mean arterial pressure, heart rate, contractility and relaxation and increased left ventricular end diastolic pressure. Isoproterenol also significantly (p < 0.05) decreased antioxidants, superoxide dismutase, catalase, glutathione peroxidase, glutathione and increased leakage of cardiac injury markers; creatine phosphokinase-MB isoenzyme, lactate dehydrogenase concomitant to increased lipid peroxidation and histopathological perturbations. However, pretreatment with A. paniculata favorably restored hemodynamic parameters and left ventricular function and significantly (p < 0.05) prevented the depletion of endogenous antioxidants and myocyte marker enzymes as well as inhibited lipid peroxidation. Significant (p < 0.05) reversal of almost all the hemodynamic, biochemical and histopathological parameters by A. paniculata pretreatment in isoproterenol-induced cardiotoxicity depicted the cardioprotective effect of A. paniculata. Results showed that A. paniculata protected heart against cardiotoxic effects of isoproterenol by boosting endogenous antioxidant network, restoring ventricular function and maintaining structural integrity of heart.
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
Effective technologies for noninvasive remote monitoring in heart failure.
Conway, Aaron; Inglis, Sally C; Clark, Robyn A
2014-06-01
Trials of new technologies to remotely monitor for signs and symptoms of worsening heart failure are continually emerging. The extent to which technological differences impact the effectiveness of noninvasive remote monitoring for heart failure management is unknown. This study examined the effect of specific technology used for noninvasive remote monitoring of people with heart failure on all-cause mortality and heart failure-related hospitalizations. A subanalysis of a large systematic review and meta-analysis was conducted. Studies were stratified according to the specific type of technology used, and separate meta-analyses were performed. Four different types of noninvasive remote monitoring technologies were identified, including structured telephone calls, videophone, interactive voice response devices, and telemonitoring. Only structured telephone calls and telemonitoring were effective in reducing the risk of all-cause mortality (relative risk [RR]=0.87; 95% confidence interval [CI], 0.75-1.01; p=0.06; and RR=0.62; 95% CI, 0.50-0.77; p<0.0001, respectively) and heart failure-related hospitalizations (RR=0.77; 95% CI, 0.68-0.87; p<0.001; and RR=0.75; 95% CI, 0.63-0.91; p=0.003, respectively). More research data are required for videophone and interactive voice response technologies. This subanalysis identified that only two of the four specific technologies used for noninvasive remote monitoring in heart failure improved outcomes. When results of studies that involved these disparate technologies were combined in previous meta-analyses, significant improvements in outcomes were identified. As such, this study has highlighted implications for future meta-analyses of randomized controlled trials focused on evaluating the effectiveness of remote monitoring in heart failure.
Sun, Huan; Wang, Yanjing; Zhang, Zhenming; Liu, Lin; Yang, Ping
2015-04-01
Determining the location of the interatrial septum (IAS) is crucial for cardiac electrophysiology procedures. Empirical methods of predicting IAS orientation depend on anatomical landmarks, including determining it from the direction of the coronary sinus (CS) and the position of the heart (e.g., vertical or transverse). However, the reliability of these methods for predicting IAS rotation warrants further study. The purpose of this study was to assess the clinical utility of the relationship between IAS orientation, CS direction, and heart position. Data from 115 patients undergoing coronary computed tomography (CT) angiography with no evidence of cardiac structural disease were collected and analyzed. Angulations describing IAS orientation, CS direction, and heart position were measured. The relationships between IAS orientation and each of the other two parameters were subsequently analyzed. The mean angulations for IAS orientation, CS direction, and heart position were 36.8 ± 7.3° (range 19.1-53.6), 37.7 ± 6.6° (range 21.3-50.1), and 37.1 ± 8.3° (range 19.2-61.0), respectively. We found a significant correlation between IAS orientation and CS direction (r = 0.928; P < 0.01), and the linear regression equation was drawn: IAS orientation = 2.01 + 1.03 × CS direction (r(2) = 0.86). No correlation was observed between IAS orientation and heart position (P = 0.86). In patients without structural heart disease, CS direction may be a reliable predictor of IAS orientation, and may serve as a helpful reference for clinicians during invasive electrophysiological procedures. Further study is warranted to clarify the relationship between IAS orientation and heart position. © 2015 Wiley Periodicals, Inc.
Cigarette Smoking and Incident Heart Failure: Insights From the Jackson Heart Study.
Kamimura, Daisuke; Cain, Loretta R; Mentz, Robert J; White, Wendy B; Blaha, Michael J; DeFilippis, Andrew P; Fox, Ervin R; Rodriguez, Carlos J; Keith, Rachel J; Benjamin, Emelia J; Butler, Javed; Bhatnagar, Aruni; Robertson, Rose M; Winniford, Michael D; Correa, Adolfo; Hall, Michael E
2018-06-12
Cigarette smoking has been linked with several factors associated with cardiac dysfunction. We hypothesized that cigarette smoking is associated with left ventricular (LV) structure and function, and incident heart failure (HF) hospitalization. We investigated 4129 (never smoker n=2884, current smoker n=503, and former smoker n=742) black participants (mean age, 54 years; 63% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study. We examined the relationships between cigarette smoking and LV structure and function by using cardiac magnetic resonance imaging among 1092 participants, cigarette smoking and brain natriuretic peptide levels among 3325 participants, and incident HF hospitalization among 3633 participants with complete data. After adjustment for confounding factors, current smoking was associated with higher mean LV mass index and lower mean LV circumferential strain ( P <0.05, for both) in comparison with never smoking. Smoking status, intensity, and burden were associated with higher mean brain natriuretic peptide levels (all P <0.05). Over 8.0 years (7.7-8.0) median follow-up, there were 147 incident HF hospitalizations. After adjustment for traditional risk factors and incident coronary heart disease, current smoking (hazard ratio, 2.82; 95% confidence interval, 1.71-4.64), smoking intensity among current smokers (≥20 cigarettes/d: hazard ratio, 3.48; 95% confidence interval, 1.65-7.32), and smoking burden among ever smokers (≥15 pack-years: hazard ratio, 2.06; 95% confidence interval, 1.29-3.3) were significantly associated with incident HF hospitalization in comparison with never smoking. In blacks, cigarette smoking is an important risk factor for LV hypertrophy, systolic dysfunction, and incident HF hospitalization even after adjusting for effects on coronary heart disease. © 2018 American Heart Association, Inc.
CFD simulation of flow through heart: a perspective review.
Khalafvand, S S; Ng, E Y K; Zhong, L
2011-01-01
The heart is an organ which pumps blood around the body by contraction of muscular wall. There is a coupled system in the heart containing the motion of wall and the motion of blood fluid; both motions must be computed simultaneously, which make biological computational fluid dynamics (CFD) difficult. The wall of the heart is not rigid and hence proper boundary conditions are essential for CFD modelling. Fluid-wall interaction is very important for real CFD modelling. There are many assumptions for CFD simulation of the heart that make it far from a real model. A realistic fluid-structure interaction modelling the structure by the finite element method and the fluid flow by CFD use more realistic coupling algorithms. This type of method is very powerful to solve the complex properties of the cardiac structure and the sensitive interaction of fluid and structure. The final goal of heart modelling is to simulate the total heart function by integrating cardiac anatomy, electrical activation, mechanics, metabolism and fluid mechanics together, as in the computational framework.
Echocardiographic examinations of 60 African grey parrots and 30 other psittacine birds.
Pees, M; Straub, J; Krautwald-Junghanns, M-E
2004-07-17
The aim of this study was to establish reference values for the assessment of cardiac function in birds by measuring structures in the heart of healthy psittacine birds; 60 grey parrots, 10 Amazon parrots, 10 cockatoos and 10 Senegal parrots were anaesthetised with isoflurane and examined echocardiographically. The heart was visualised in two planes (vertical and horizontal views). Depending on the quality of the images, several dimensions of the heart could be measured and various parameters calculated. On the basis of these values, it was possible to establish reference values for each parrot genus. Some relative parameters showed no significant difference between the genera, independent of the bird's size.
NASA Astrophysics Data System (ADS)
Edemskii, M. L.; Kogan, V. A.
1981-07-01
Relative to its major function, pumping, the heart should be considered as an integral musculovascular organ. It is precisely this integration in the structural and functional sense which permits the heart not only to perform its pump function as a converter of chemical energy supplied by the blood into mechanical flow energy but also to combine the supply and conversion of energy into a single cycle, produce the hydrodynamics of cardiac output in definite fashion, and introduce a correction into the filling phase according to current arterial pressure as the most dynamic index of systemic hemodynamics. The breakdown of the structure of the cardiac pump into elements differing in their functional significance permits us to delineate at least three channels for the utilization of energy supplied to the heart and consumed in the major pumping function: the mechanical work performed by the lower part of the cardiac muscle that is displaced into the ventricular space, the energy consumed on maintaining the systolic pressure of the myocardial fibers which form the relatively immobile upper and side walls of the heart, and the energy consumed on maintaining the high tone of the muscular walls of the coronary arteries and arterioles which form the hydraulic frame of the heart. A representation of the heart which includes muscular and vascular components, in our view, is the basic prerequisite for the development of mathematical models for the cardiac pump based on energy balance equations and suitable for solving the problems posed by clinical medicine in regard to auxiliary blood circulation.
System overview of the fully implantable destination therapy--ReinHeart-total artificial heart.
Pelletier, Benedikt; Spiliopoulos, Sotirios; Finocchiaro, Thomas; Graef, Felix; Kuipers, Kristin; Laumen, Marco; Guersoy, Dilek; Steinseifer, Ulrich; Koerfer, Reiner; Tenderich, Gero
2015-01-01
Owing to the lack of suitable allografts, the demand for long-term mechanical circulatory support in patients with biventricular end-stage heart failure is rising. Currently available Total Artificial Heart (TAH) systems consist of pump units with only limited durability, percutaneous tubes and bulky external equipment that limit the quality of life. Therefore we are focusing on the development of a fully implantable, highly durable destination therapy total artificial heart. The ReinHeart-TAH system consists of a passively filling pump unit driven by a low-wear linear drive between two artificial ventricles, an implantable control unit and a compliance chamber. The TAH is powered by a transcutaneous energy transmission system. The flow distribution inside the ventricles was analysed by fluid structure interaction simulation and particle image velocimetry measurements. Along with durability tests, the hydrodynamic performance and flow balance capability were evaluated in a mock circulation loop. Animal trials are ongoing. Based on fluid structure interaction simulation and particle image velocimetry, blood stagnation areas have been significantly reduced. In the mock circulation loop the ReinHeart-TAH generated a cardiac output of 5 l/min at an operating frequency of 120 bpm and an aortic pressure of 120/80 mmHg. The highly effective preload sensitivity of the passively filling ventricles allowed the sensorless integration of the Frank Starling mechanism. The ReinHeart-TAH effectively replaced the native heart's function in animals for up to 2 days. In vitro and in vivo testing showed a safe and effective function of the ReinHeart-TAH system. This has the potential to become an alternative to transplantation. However, before a first-in-man implant, chronic animal trials still have to be completed. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Kamensky, David; Hsu, Ming-Chen; Schillinger, Dominik; Evans, John A.; Aggarwal, Ankush; Bazilevs, Yuri; Sacks, Michael S.; Hughes, Thomas J. R.
2014-01-01
In this paper, we develop a geometrically flexible technique for computational fluid–structure interaction (FSI). The motivating application is the simulation of tri-leaflet bioprosthetic heart valve function over the complete cardiac cycle. Due to the complex motion of the heart valve leaflets, the fluid domain undergoes large deformations, including changes of topology. The proposed method directly analyzes a spline-based surface representation of the structure by immersing it into a non-boundary-fitted discretization of the surrounding fluid domain. This places our method within an emerging class of computational techniques that aim to capture geometry on non-boundary-fitted analysis meshes. We introduce the term “immersogeometric analysis” to identify this paradigm. The framework starts with an augmented Lagrangian formulation for FSI that enforces kinematic constraints with a combination of Lagrange multipliers and penalty forces. For immersed volumetric objects, we formally eliminate the multiplier field by substituting a fluid–structure interface traction, arriving at Nitsche’s method for enforcing Dirichlet boundary conditions on object surfaces. For immersed thin shell structures modeled geometrically as surfaces, the tractions from opposite sides cancel due to the continuity of the background fluid solution space, leaving a penalty method. Application to a bioprosthetic heart valve, where there is a large pressure jump across the leaflets, reveals shortcomings of the penalty approach. To counteract steep pressure gradients through the structure without the conditioning problems that accompany strong penalty forces, we resurrect the Lagrange multiplier field. Further, since the fluid discretization is not tailored to the structure geometry, there is a significant error in the approximation of pressure discontinuities across the shell. This error becomes especially troublesome in residual-based stabilized methods for incompressible flow, leading to problematic compressibility at practical levels of refinement. We modify existing stabilized methods to improve performance. To evaluate the accuracy of the proposed methods, we test them on benchmark problems and compare the results with those of established boundary-fitted techniques. Finally, we simulate the coupling of the bioprosthetic heart valve and the surrounding blood flow under physiological conditions, demonstrating the effectiveness of the proposed techniques in practical computations. PMID:25541566
Abnormal myocardial fluid retention as an early manifestation of ischemic injury.
Willerson, J. T.; Scales, F.; Mukherjee, A.; Platt, M.; Templeton, G. H.; Fink, G. S.; Buja, L. M.
1977-01-01
Fifty-seven isolated, blood perfused, continuously weighed canine hearts have been utilized to study the development of abnormal myocardial fluid retention during early myocardial ischemic injury. Inflatable balloon catheters were positioned around the left anterior descending coronary arteries (LAD) of 54 hearts or the proximal left circumflex coronary arteries of three hearts for study of the following intervals of coronary occlusion: a) 10 minutes followed by 20 minutes of reflow, b) 40 minutes followed by either no reflow or by 20 minutes of reflow, and c) 60 minutes without reflow. After 60 minutes of fixed coronary occlusion, histologic and ultrastructural examination revealed mild swelling of many ischemic cardiac muscle cells in the absence of interstitial edema, cardiac weight gain, and obvious structural defects in cell membrane integrity. After 40 minutes of coronary occlusion and 20 minutes of reflow, significant cardiac weight gain occurred in association with characteristic alterations in the ischemic region, including widespread interstitial edema and focal vascular congestion and hemorrhage and swelling of cardiac muscle cells. Focal structural defects in cell membrane integrity were also noted. The development of abnormal myocardial fluid retention after 40 minutes of LAD occlusion occurred in association with a significant reduction in sodium-potassium-ATPase activity in the ischemic area, but with no significant alteration in either creatine phosphokinase or citrate synthase activity in the same region. Despite the abnormal myocardial fluid retention in these hearts, it was possible pharmacologically to vasodilate coronary vessels with adenosine and nitroglycerin infusion to maintain a consistently high coronary flow following release of the coronary occlusion after 40 minutes and to even exceed initial hyperemic flow values following release of the occlusion when adenosine and nitroglycerin infusion was delayed until 15 minutes after reflow. Thus, the data indicate that impaired cell volume regulation and interstitial fluid accumulation and focal structural defects in cell membrane integrity are early manifestations of ischemic injury followed by reflow, but fail to establish a major role for the abnormal fluid retention in altering coronary blood flow prior to the development of extensive myocardial necrosis. In contrast, fixed coronary occlusion for 60 minutes results in mild intracellular swelling but no significant interstitial edema and no obvious structural defects in cell membrane integrity. Images Figure 1 Figure 5 Figure 6 Figure 2 Figure 3 Figure 4 PMID:139829
Wang, Xiaohong; Hu, Qingsong; Nakamura, Yasuhiro; Lee, Joseph; Zhang, Ge; From, Arthur H L; Zhang, Jianyi
2006-07-01
Cardiac stem cell-like populations exist in adult hearts, and their roles in cardiac repair remain to be defined. Sca-1 is an important surface marker for cardiac and other somatic stem cells. We hypothesized that heart-derived Sca-1(+)/CD31(-) cells may play a role in myocardial infarction-induced cardiac repair/remodeling. Mouse heart-derived Sca-1(+)/CD31(-) cells cultured in vitro could be induced to express both endothelial cell and cardiomyocyte markers. Immunofluorescence staining and fluorescence-activated cell sorting analysis indicated that endogenous Sca-1(+)/CD31(-) cells were significantly increased in the mouse heart 7 days after myocardial infarction (MI). Western blotting confirmed elevated Sca-1 protein expression in myocardium 7 days after MI. Transplantation of Sca-1(+)/CD31(-) cells into the acutely infarcted mouse heart attenuated the functional decline and adverse structural remodeling initiated by MI as evidenced by an increased left ventricular (LV) ejection fraction, a decreased LV end-diastolic dimension, a decreased LV end-systolic dimension, a significant increase of myocardial neovascularization, and modest cardiomyocyte regeneration. Attenuation of LV remodeling was accompanied by remarkably improved myocardial bioenergetic characteristics. The beneficial effects of cell transplantation appear to primarily depend on paracrine effects of the transplanted cells on new vessel formation and native cardiomyocyte function. Sca-1(+)/CD31(-) cells may hold therapeutic possibilities with regard to the treatment of ischemic heart disease.
Sanchez-Garcia, M Esther; Ramirez-Lara, Irene; Gomez-Delgado, Francisco; Yubero-Serrano, Elena M; Leon-Acuña, Ana; Marin, Carmen; Alcala-Diaz, Juan F; Camargo, Antonio; Lopez-Moreno, Javier; Perez-Martinez, Pablo; Tinahones, Francisco José; Ordovas, Jose M; Caballero, Javier; Blanco-Molina, Angeles; Lopez-Miranda, Jose; Delgado-Lista, Javier
2018-02-23
Microcirculation disturbances have been associated to most of the cardiovascular risk factors as well as to multiple inflammatory diseases. However, whether these abnormalities are specifically augmented in patients with coronary heart disease is still unknown. We aimed to evaluate if there is a relationship between the presence of coronary heart disease and the existence of functional and structural capillary abnormalities evaluated in the cutaneous microcirculation by videocapillaroscopy. Two matched samples of 30 participants with and without coronary heart disease but with similar clinical and anthropometric characteristics were evaluated by videocapillaroscopy at the dorsal skin of the third finger of the non-dominant hand. We calculated basal capillary density as well as capillary density after a period of arterial and venous occlusion in order to evaluate functionality and maximum capillary density. We also measured capillary recruitment. Microvascular capillary density at rest was significantly lower in patients suffering from coronary heart disease than in controls. This fact was also found after dynamic tests (arterial and venous occlusion), suggesting functional impairments. Capillary recruitment of the samples was not different in our sample. In our study, patients with coronary heart disease exhibit functional and structural microvascular disturbances. Although this is a very preliminary study, these findings open the door for further studying the microvascular functionality in coronary patients and how it relates to the response to treatment and/or the prognosis of the disease. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
NASA Astrophysics Data System (ADS)
Yu, Siyao; Gu, Shi; Zhao, Xiaowei; Liu, Yehe; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.
2017-02-01
Congenital heart defects (CHDs) are the most common birth defect, affecting between 4 and 75 per 1,000 live births depending on the inclusion criteria. Many of these defects can be traced to defects of cardiac cushions, critical structures during development that serve as precursors to many structures in the mature heart, including the atrial and ventricular septa, and all four sets of cardiac valves. Epithelial-mesenchymal transition (EMT) is the process through which cardiac cushions become populated with cells. Altered cushion size or altered cushion cell density has been linked to many forms of CHDs, however, quantitation of cell density in the complex 3D cushion structure poses a significant challenge to conventional histology. Optical coherence tomography (OCT) is a technique capable of 3D imaging of the developing heart, but typically lacks the resolution to differentiate individual cells. Our goal is to develop an algorithm to quantitatively characterize the density of cells in the developing cushion using 3D OCT imaging. First, in a heart volume, the atrioventricular (AV) cushions were manually segmented. Next, all voxel values in the region of interest were pooled together to generate a histogram. Finally, two populations of voxels were classified using either K-means classification, or a Gaussian mixture model (GMM). The voxel population with higher values represents cells in the cushion. To test the algorithm, we imaged and evaluated avian embryonic hearts at looping stages. As expected, our result suggested that the cell density increases with developmental stages. We validated the technique against scoring by expert readers.
TU-EF-304-04: A Heart Motion Model for Proton Scanned Beam Chest Radiotherapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
White, B; Kiely, J Blanco; Lin, L
Purpose: To model fast-moving heart surface motion as a function of cardiac-phase in order to compensate for the lack of cardiac-gating in evaluating accurate dose to coronary structures. Methods: Ten subjects were prospectively imaged with a breath-hold, cardiac-gated MRI protocol to determine heart surface motion. Radial and planar views of the heart were resampled into a 3-dimensional volume representing one heartbeat. A multi-resolution optical flow deformable image registration algorithm determined tissue displacement during the cardiac-cycle. The surface of the heart was modeled as a thin membrane comprised of voxels perpendicular to a pencil beam scanning (PBS) beam. The membrane’s out-of-planemore » spatial displacement was modeled as a harmonic function with Lame’s equations. Model accuracy was assessed with the root mean squared error (RMSE). The model was applied to a cohort of six chest wall irradiation patients with PBS plans generated on phase-sorted 4DCT. Respiratory motion was separated from the cardiac motion with a previously published technique. Volumetric dose painting was simulated and dose accumulated to validate plan robustness (target coverage variation accepted within 2%). Maximum and mean heart surface dose assessed the dosimetric impact of heart and coronary artery motion. Results: Average and maximum heart surface displacements were 2.54±0.35mm and 3.6mm from the end-diastole phase to the end-systole cardiac-phase respectively. An average RMSE of 0.11±0.04 showed the model to be accurate. Observed errors were greatest between the circumflex artery and mitral valve level of the heart anatomy. Heart surface displacements correspond to a 3.6±1.0% and 5.1±2.3% dosimetric impact on the maximum and mean heart surface DVH indicators respectively. Conclusion: Although heart surface motion parallel to beam’s direction was substantial, its maximum dosimetric impact was 5.1±2.3%. Since PBS delivers low doses to coronary structures relative to photon radiotherapy, it is unknown whether this variation would be clinically significant for late effects.« less
Kocica, Mladen J; Corno, Antonio F; Carreras-Costa, Francesc; Ballester-Rodes, Manel; Moghbel, Mark C; Cueva, Clotario N C; Lackovic, Vesna; Kanjuh, Vladimir I; Torrent-Guasp, Francisco
2006-04-01
We are currently witnessing the advent of new diagnostic tools and therapies for heart diseases, but, without serious scientific consensus on fundamental questions about normal and diseased heart structure and function. During the last decade, three successive, international, multidisciplinary symposia were organized in order to setup fundamental research principles, which would allow us to make a significant step forward in understanding heart structure and function. Helical ventricular myocardial band of Torrent-Guasp is the revolutionary new concept in understanding global, three-dimensional, functional architecture of the ventricular myocardium. This concept defines the principal, cumulative vectors, integrating the tissue architecture (i.e. form) and net forces developed (i.e. function) within the ventricular mass. Here we expose the compendium of Torrent-Guasp's half-century long functional anatomical investigations in the light of ongoing efforts to define the integrative approach, which would lead to new understanding of the ventricular form and function by linking across multiple scales of biological organization, as defined in ongoing Physiome project. Helical ventricular myocardial band of Torrent-Guasp may also, hopefully, allow overcoming some difficulties encountered in contemporary efforts to create a comprehensive mathematical model of the heart.
Zeng, Xianxu; Tate, Rebecca E.; McKee, Mary L.; Capen, Diane E.; Zhang, Zhan; Tanzi, Rudolph E.; Zhou, Chao
2015-01-01
Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential role in heart morphogenesis and function. PMID:26348211
Geographic differences in heart failure trials.
Ferreira, João Pedro; Girerd, Nicolas; Rossignol, Patrick; Zannad, Faiez
2015-09-01
Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.
Maturation status of sarcomere structure and function in human iPSC-derived cardiac myocytes.
Bedada, Fikru B; Wheelwright, Matthew; Metzger, Joseph M
2016-07-01
Human heart failure due to myocardial infarction is a major health concern. The paucity of organs for transplantation limits curative approaches for the diseased and failing adult heart. Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) have the potential to provide a long-term, viable, regenerative-medicine alternative. Significant progress has been made with regard to efficient cardiac myocyte generation from hiPSCs. However, directing hiPSC-CMs to acquire the physiological structure, gene expression profile and function akin to mature cardiac tissue remains a major obstacle. Thus, hiPSC-CMs have several hurdles to overcome before they find their way into translational medicine. In this review, we address the progress that has been made, the void in knowledge and the challenges that remain. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J
2017-01-01
Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os ; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma b rain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10-0.12) with the mid- and high-dose carvedilol treatment. A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model.
Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J
2017-01-01
Introduction: Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Methods: Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Results: Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma brain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10–0.12) with the mid- and high-dose carvedilol treatment. Conclusion: A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model. PMID:28491305
Organ, Chelsea L; Otsuka, Hiroyuki; Bhushan, Shashi; Wang, Zeneng; Bradley, Jessica; Trivedi, Rishi; Polhemus, David J; Tang, W H Wilson; Wu, Yuping; Hazen, Stanley L; Lefer, David J
2016-01-01
Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients, is both elevated in the circulation of patients having heart failure and heralds worse overall prognosis. In animal studies, dietary choline or TMAO significantly accelerates atherosclerotic lesion development in ApoE-deficient mice, and reduction in TMAO levels inhibits atherosclerosis development in the low-density lipoprotein receptor knockout mouse. C57BL6/J mice were fed either a control diet, a diet containing choline (1.2%) or a diet containing TMAO (0.12%) starting 3 weeks before surgical transverse aortic constriction. Mice were studied for 12 weeks after transverse aortic constriction. Cardiac function and left ventricular structure were monitored at 3-week intervals using echocardiography. Twelve weeks post transverse aortic constriction, myocardial tissues were collected to evaluate cardiac and vascular fibrosis, and blood samples were evaluated for cardiac brain natriuretic peptide, choline, and TMAO levels. Pulmonary edema, cardiac enlargement, and left ventricular ejection fraction were significantly (P<0.05, each) worse in mice fed either TMAO- or choline-supplemented diets when compared with the control diet. In addition, myocardial fibrosis was also significantly greater (P<0.01, each) in the TMAO and choline groups relative to controls. Heart failure severity is significantly enhanced in mice fed diets supplemented with either choline or the gut microbe-dependent metabolite TMAO. The present results suggest that additional studies are warranted examining whether gut microbiota and the dietary choline → TMAO pathway contribute to increased heart failure susceptibility. © 2015 American Heart Association, Inc.
Domingo, Cristina; Aros, Fernando; Otxandategi, Agurtzane; Beistegui, Idoia; Besga, Ariadna; Latorre, Pedro María
2018-02-26
To assess the efficacy of the ProMIC, multidisciplinary program for patients admitted at hospital because of heart failure (HF) programme, in reducing the HF-related readmission rate. Quasi-experimental research with control group. Twelve primary health care centres and 3 hospitals from the Basque Country. Aged 40 years old or above patients admitted for HF with a New York Heart Association functional class II to IV. Patients in the intervention group carried out the ProMIC programme, a structured clinical intervention based on clinical guidelines and on the chronic care model. Control group received usual care. The rate of readmission for HF and health-related quality of life RESULTS: One hundred fifty five patients were included in ProMIC group and 129 in control group. 45 rehospitalisation due to heart failure happened in ProMIC versus 75 in control group (adjusted hazard ratio=0.59, CI 95%: 0.36-0.98; P=.049). There were significant differences in specific quality of life al 6 months. No significant differences were found in rehospitalisation due to all causes, due to cardiovascular causes, visits to emergency room, mortality, the combined variable of these events, the functional capacity or quality of life at 12 months of follow up. ProMIC reduces significantly heart failure rehospitalisation and improve quality of life al 6 months of follow up. No significant differences were found in the rests of variables. Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.
Methods to assess Drosophila heart development, function and aging
Ocorr, Karen; Vogler, Georg; Bodmer, Rolf
2014-01-01
In recent years the Drosophila heart has become an established model of many different aspects of human cardiac disease. This model has allowed identification of disease-causing mechanisms underlying congenital heart disease and cardiomyopathies and has permitted the study underlying genetic, metabolic and age-related contributions to heart function. In this review we discuss methods currently employed in the analysis of the Drosophila heart structure and function, such as optical methods to infer heart function and performance, electrophysiological and mechanical approaches to characterize cardiac tissue properties, and conclude with histological techniques used in the study of heart development and adult structure. PMID:24727147
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil
Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy.more » During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.« less
Contemporary management of tricuspid regurgitation: an updated clinical review.
Taylor, Joshua T; Chidsey, Geoffrey; Disalvo, Thomas G; Byrne, John G; Maltais, Simon
2013-01-01
Tricuspid regurgitation (TR) is a complex and insidious valvular pathology that represents a complex decision and management algorithm for patients. TR is present in a significant proportion of the population and is especially prevalent in patients with advanced heart failure. Patients with TR have been demonstrated to have a decreased survival even with normal left heart function. TR can be a result of pathology that directly affects the valvular structure (i.e., Ebstein anomaly) or as a result of increased forward pressures (ie, pulmonary hypertension, left heart failure). Conservative management of patients with TR is primarily symptomatic relief. Definitive therapy involves surgical repair of the tricuspid valve. Furthermore, as more patients develop advanced heart failure, the management of TR in patients with left ventricular assist devices has become necessary because of the evidence of increased in-hospital morbidity and a trend toward decreased survival.
Amann, Kerstin; Törnig, Johannes; Buzello, Mareike; Kuhlmann, Alexander; Gross, Marie-Luise; Adamczak, Marcin; Buzello, Moriz; Ritz, Eberhard
2002-09-01
Chronic renal failure is characterized by remodeling of the structure of the heart and the vasculature, for example, left ventricular hypertrophy, myocardial fibrosis, capillary/myocyte mismatch, as well as thickening of intramyocardial arteries and of peripheral arteries and veins. Furthermore, uremia is a state of increased oxygen stress. It was the purpose of this study to examine whether these findings are interrelated. To investigate whether antioxidative therapy with dl-alpha-tocopherol (Toco; vitamin E) interferes with the development of abnormal cardiovascular structure in experimental renal failure, 28 male Sprague-Dawley rats were subjected to partial renal ablation (subtotal nephrectomy, SNX) or to sham operation (sham). SNX were either left untreated or received the antioxidant Toco (2 x 1500 IE/kg BW/week in the pellets). Blood pressure was measured using tail plethysmography. The experiment was terminated after 12 weeks. Heart and left ventricular weight were determined and the following parameters were measured using morphometry and stereology: volume densities of cardiomyocytes, capillaries and non-vascular interstitium; length density and total length of cardiac capillaries, wall thickness of intramyocardial arterioles and of the aorta. Systolic blood pressure and body weight were comparable in all groups. Treatment with Toco led to significantly increased plasma concentrations of Toco. Left ventricular weight and wall thickness of intramyocardial arteries were significantly higher in both SNX groups compared to sham controls. Volume density of the cardiac interstitial tissue was significantly higher in untreated SNX than in Toco treated SNX and sham control rats. Length density of capillaries was significantly lower in untreated SNX than in control rats; however, the values were significantly higher, and even higher than in sham controls, when SNX were treated with Toco. Treatment with the antioxidant dl-alpha-tocopherol prevented cardiomyocyte/capillary mismatch, and to some extent also myocardial fibrosis in rats with renal failure. The results point to a role of oxidative stress in the genesis of myocardial interstitial fibrosis and capillary deficit of the heart.
Avnet, Hagai; Mazaaki, Eyal; Shen, Ori; Cohen, Sarah; Yagel, Simcha
2016-01-01
We aimed to evaluate the use of spatiotemporal image correlation (STIC) as a tool for training nonexpert examiners to perform screening examinations of the fetal heart by acquiring and examining STIC volumes according to a standardized questionnaire based on the 5 transverse planes of the fetal heart. We conducted a prospective study at 2 tertiary care centers. Two sonographers without formal training in fetal echocardiography received theoretical instruction on the 5 fetal echocardiographic transverse planes, as well as STIC technology. Only women with conditions allowing 4-dimensional STIC volume acquisitions (grayscale and Doppler) were included in the study. Acquired volumes were evaluated offline according to a standardized protocol that required the trainee to mark 30 specified structures on 5 required axial planes. Volumes were then reviewed by an expert examiner for quality of acquisition and correct identification of specified structures. Ninety-six of 112 pregnant women examined entered the study. Patients had singleton pregnancies between 20 and 32 weeks' gestation. After an initial learning curve of 20 examinations, trainees succeeded in identifying 97% to 98% of structures, with a highly significant degree of agreement with the expert's analysis (P < .001). A median of 2 STIC volumes for each examination was necessary for maximal structure identification. Acquisition quality scores were high (8.6-8.7 of a maximal score of 10) and were found to correlate with identification rates (P = .017). After an initial learning curve and under expert guidance, STIC is an excellent tool for trainees to master extended screening examinations of the fetal heart.
Thaden, Jeremy J; Sanon, Saurabh; Geske, Jeffrey B; Eleid, Mackram F; Nijhof, Niels; Malouf, Joseph F; Rihal, Charanjit S; Bruce, Charles J
2016-06-01
There has been significant growth in the volume and complexity of percutaneous structural heart procedures in the past decade. Increasing procedural complexity and accompanying reliance on multimodality imaging have fueled the development of fusion imaging to facilitate procedural guidance. The first clinically available system capable of echocardiographic and fluoroscopic fusion for real-time guidance of structural heart procedures was approved by the US Food and Drug Administration in 2012. Echocardiographic-fluoroscopic fusion imaging combines the precise catheter and device visualization of fluoroscopy with the soft tissue anatomy and color flow Doppler information afforded by echocardiography in a single image. This allows the interventionalist to perform precise catheter manipulations under fluoroscopy guidance while visualizing critical tissue anatomy provided by echocardiography. However, there are few data available addressing this technology's strengths and limitations in routine clinical practice. The authors provide a critical review of currently available echocardiographic-fluoroscopic fusion imaging for guidance of structural heart interventions to highlight its strengths, limitations, and potential clinical applications and to guide further research into value of this emerging technology. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
HIV and Nonischemic Heart Disease.
Manga, Pravin; McCutcheon, Keir; Tsabedze, Nqoba; Vachiat, Ahmed; Zachariah, Don
2017-01-03
Human immunodeficiency virus (HIV)-associated heart disease encompasses a broad spectrum of diseases. HIV infection may involve the pericardium, myocardium, coronary arteries, pulmonary vasculature, and valves, as well as the systemic vasculature. Access to combination antiretroviral therapy, as well as health resources, has had a significant influence on the prevalence and severity of the effects on each cardiac structure. Investigations over the recent past have improved our understanding of the epidemiology and pathophysiology of HIV-associated cardiovascular disease. This review will focus on our current understanding of pathogenesis and risk factors associated with HIV infection and heart disease, and it will discuss relevant advances in diagnosis and management of these conditions. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
[Recurrence plot analysis of HRV for brain ischemia and asphyxia].
Chen, Xiaoming; Qiu, Yihong; Zhu, Yisheng
2008-02-01
Heart rate variability (HRV) is the tiny variability existing in the cycles of the heart beats, which reflects the corresponding balance between sympathetic and vagus nerves. Since the nonlinear characteristic of HRV is confirmed, the Recurrence Plot method, a nonlinear dynamic analysis method based on the complexity, could be used to analyze HRV. The results showed the recurrence plot structures and some quantitative indices (L-Mean, L-Entr) during asphyxia insult vary significantly as compared to those in normal conditions, which offer a new method to monitor brain asphyxia injury.
Verdurmen, Kim M J; Lempersz, Carlijn; Vullings, Rik; Schroer, Christian; Delhaas, Tammo; van Laar, Judith O E H; Oei, S Guid
2016-08-17
The fetal anomaly ultrasound only detects 65 to 81 % of the patients with congenital heart disease, making it the most common structural fetal anomaly of which a significant part is missed during prenatal life. Therefore, we need a reliable non-invasive diagnostic method which improves the predictive value for congenital heart diseases early in pregnancy. Fetal electrocardiography could be this desired diagnostic method. There are multiple technical challenges to overcome in the conduction of the fetal electrocardiogram. In addition, interpretation is difficult due to the organisation of the fetal circulation in utero. We want to establish the normal ranges and values of the fetal electrocardiogram parameters in healthy fetuses of 18 to 24 weeks of gestation. Women with an uneventful singleton pregnancy between 18 and 24 weeks of gestation are asked to participate in this prospective cohort study. A certified and experienced sonographist performs the fetal anomaly scan. Subsequently, a fetal electrocardiogram recording is performed using dedicated signal processing methods. Measurements are performed at two institutes. We will include 300 participants to determine the normal values and 95 % confidence intervals of the fetal electrocardiogram parameters in a healthy fetus. We will evaluate the fetal heart rate, segment intervals, normalised amplitude and the fetal heart axis. Three months postpartum, we will evaluate if a newborn is healthy through a questionnaire. Fetal electrocardiography could be a promising tool in the screening program for congenital heart diseases. The electrocardiogram is a depiction of the intimate relationship between the cardiac nerve conduction pathways and the structural morphology of the fetal heart, and therefore particularly suitable for the detection of secondary effects due to a congenital heart disease (hypotrophy, hypertrophy and conduction interruption).
Nekouei, Zohreh Khayyam; Doost, Hamid Taher Neshat; Yousefy, Alireza; Manshaee, Gholamreza; Sadeghei, Masoumeh
2014-01-01
Although psychological factors are now recognized as playing a significant and independent role in the development of coronary heart disease (CHD) and its complications, many of these factors are correlated with each other. The present study is aimed at examining the association between alexithymia and anxiety depression, stress, quality of life, and social support in CHD patients. In this research 398 patients with coronary heart disease (166 females and 232 males) from the city of Isfahan were selected using random sampling. The tools used included depression, anxiety, and stress scale (DASS-21), Health-related to Quality Of Life (HRQOL-26), Multiple Scale Perceived Social Support (MSPSS-12), and the Toronto Alexithymia Scale (TAS-20). The data were analyzed using structural equation modeling by using the Statistical Package for Social Science (SPSS21) (IBM Corp: Armonk, New York.U.S.) and Asset Management Operating System (AMOS21) SPSS, an IBM Company: Chicago, U.S. Software. Results of the structural equation model showed an acceptable goodness of fit, for the explanation alexithymia that was significantly associated with lower HRQOL and social support and increasing anxiety, depression, and stress. Alexithymia may increase anxiety, depression, and stress and can be a predisposing factor to poorer HRQOL and social support.
NASA Astrophysics Data System (ADS)
Gu, Shi; Peterson, Lindsy M.; Ma, Pei; Karunamuni, Ganga; Watanabe, Michiko; Jenkins, Michael W.; Rollins, Andrew M.
2016-03-01
Fetal alcohol syndrome commonly results in neurological and craniofacial defects, additionally, as high as 54% of live-born children with this syndrome also possess cardiac abnormalities. We have previously shown that CNCC-ablated embryos exhibit similar structural and functional phenotypes as ethanol-exposed embryos. Here, we present progress on two fronts toward understanding the association between CNCC dysfunction and FAS-related CHDs. We have developed a technique for measuring the thickness of the cardiac cushions throughout the heart. These values were then mapped onto a surface mesh of the myocardial wall for 3-D visualization. The cushions were observed to be significantly reduced in the outflow tract of CNCC-ablated embryos. We also observed a correlation between abnormal pulsed Doppler waveforms and increased separation of the atrioventricular inferior and superior cushions. This correlation between function and structure will enable rapid phenotyping of perturbed embryos. Finally, we present our preliminary results using methyl donors to rescue ethanol-exposed embryonic CHDs. Betaine was administered along with the ethanol injection to embryos at 21 hours of development. The embryos were then analyzed at day 8 for survival and heart morphology. The administration of betaine resulted in a significant increase in survival and normalization of atrioventricular valve leaflet volume and interventricular septum thickness.
Wang, Shan-Shan; Hong, Wen-Jing; Zhang, Yu-Qi; Chen, Shu-Bao; Huang, Guo-Ying; Zhang, Hong-Yan; Chen, Li-Jun; Wu, Lan-Ping; Shen, Rong; Liu, Yi-Qing; Zhu, Jun-Xue
2018-06-01
Clinical decision making in children with heart disease relies on detailed measurements of cardiac structures using two-dimensional and M-mode echocardiography. However, no echocardiographic reference values are available for the Chinese children. We aimed to establish z-score regression equations for left heart structures in a population-based cohort of healthy Chinese Han children. Echocardiography was performed in 545 children with a normal heart. The dimensions of the aortic valve annulus (AVA), aortic sinuses of Valsalva (ASV), sinotubular junction (STJ), ascending aorta (AAO), left atrium (LA), mitral valve annulus (MVA), interventricular septal end-diastolic thickness (IVSd), interventricular septal end-systolic thickness (IVSs), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular posterior wall end-diastolic thickness (LVPWd), left ventricular posterior wall end-systolic thickness (LVPWs) were measured. Regression analyses were conducted to relate the measurements of left heart structures to body surface area (BSA). Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were calculated. Several models were used, and the adjusted R2 values were compared for each model. AVA, ASV, STJ, AAO, LA, MVA, IVSd, IVSs, LVIDd, LVIDs, LVPWd, and LVPWs had a cubic relationship with BSA. LVEF and LVFS fell within a narrow range. Our results provide reference values for z scores and regression equations for left heart structures in Han Chinese children. These data may help make a quick and accurate judgment of the routine clinical measurement of left heart structures in children with heart disease. © 2018 Wiley Periodicals, Inc.
Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome.
Hall, Scott S; Lightbody, Amy A; McCarthy, Brigid E; Parker, Karen J; Reiss, Allan L
2012-04-01
Fragile X syndrome (FXS) is a rare inherited genetic disorder causing severe intellectual disability and autistic-like symptoms. Individuals with FXS, males in particular, often exhibit extreme eye gaze avoidance and hyperarousal when they encounter stressful social situations. We investigated whether oxytocin (OT), a hormone with prosocial and anxiolytic effects, could alleviate symptoms of social anxiety in this population. A randomized double-blind placebo-controlled single-dose trial was performed with intranasal administration of placebo, 24 IU OT and 48 IU OT. Measures of eye gaze frequency, heart rate, respiratory sinus arrhythmia (RSA), heart rate variability (HRV) and salivary cortisol were obtained during a structured social challenge conducted 50 min following OT administration. Ten low-functioning males with FXS (aged 13-28 years) traveled to Stanford for the initial visit: 8 completed the study. Eye gaze frequency improved significantly in response to the 24 IU OT dose and salivary cortisol levels decreased significantly in response to the 48 IU OT dose. There was no effect of OT on heart rate, RSA or HRV although individual plots of the heart rate data suggested that OT increased heart rate in some participants and decreased heart rate in others. These findings suggest that intranasal administration of OT may ameliorate some symptoms of social anxiety in patients with FXS. Further double-blind placebo-controlled studies of OT, conducted in combination with behavioral treatment programs, may be warranted. Copyright © 2011 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Feng, Mary, E-mail: maryfeng@umich.ed; Moran, Jean M.; Koelling, Todd
2011-01-01
Purpose: Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. Methods and Materials: A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricularmore » branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. Results: The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. Conclusions: This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.« less
... page: //medlineplus.gov/ency/article/001114.htm Congenital heart disease To use the sharing features on this page, please enable JavaScript. Congenital heart disease (CHD) is a problem with the heart's structure ...
Drug Treatment of Pulmonary Hypertension in Children
Vorhies, Erika E; Ivy, David Dunbar
2013-01-01
Pulmonary arterial hypertension (PAH) is a rare disease in infants and children that is associated with significant morbidity and mortality. The disease is characterized by progressive pulmonary vascular functional and structural changes resulting in increased pulmonary vascular resistance and eventual right heart failure and death. In the majority of pediatric patients, PAH is idiopathic or associated with congenital heart disease and rarely is associated with other conditions such as connective tissue or thromboembolic disease. Although treatment of the underlying disease and reversal of advanced structural changes has not yet been achieved with current therapy, quality of life and survival have been improved significantly. Targeted pulmonary vasodilator therapies, including endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase type 5 inhibitors, have demonstrated hemodynamic and functional improvement in children. The management of pediatric PAH remains challenging as treatment decisions continue to depend largely on results from evidence-based adult studies and the clinical experience of pediatric experts. This article reviews the current drug therapies and their use in the management of PAH in children. PMID:24114695
Early structural changes of the heart after experimental polytrauma and hemorrhagic shock
Halbgebauer, Rebecca; Eisele, Philipp; Messerer, David A. C.; Weckbach, Sebastian; Schultze, Anke; Braumüller, Sonja; Gebhard, Florian
2017-01-01
Evidence is emerging that systemic inflammation after trauma drives structural and functional impairment of cardiomyocytes and leads to cardiac dysfunction, thus worsening the outcome of polytrauma patients. This study investigates the structural and molecular changes in heart tissue 4 h after multiple injuries with additional hemorrhagic shock using a clinically relevant rodent model of polytrauma. We determined mediators of systemic inflammation (keratinocyte chemoattractant, macrophage chemotactic protein 1), activated complement component C3a and cardiac troponin I in plasma and assessed histological specimen of the mouse heart via standard histomorphology and immunohistochemistry for cellular and subcellular damage and ongoing apoptosis. Further we investigated spatial and quantitative changes of connexin 43 by immunohistochemistry and western blotting. Our results show significantly increased plasma levels of both keratinocyte chemoattractant and cardiac troponin I 4 h after polytrauma and 2 h after induction of hypovolemia. Although we could not detect any morphological changes, immunohistochemical evaluation showed increased level of tissue high-mobility group box 1, which is both a damage-associated molecule and actively released as a danger response signal. Additionally, there was marked lateralization of the cardiac gap-junction protein connexin 43 following combined polytrauma and hemorrhagic shock. These results demonstrate a molecular manifestation of remote injury of cardiac muscle cells in the early phase after polytrauma and hemorrhagic shock with marked disruption of the cardiac gap junction. This disruption of an important component of the electrical conduction system of the heart may lead to arrhythmia and consequently to cardiac dysfunction. PMID:29084268
Lalli, M J; Yong, J; Prasad, V; Hashimoto, K; Plank, D; Babu, G J; Kirkpatrick, D; Walsh, R A; Sussman, M; Yatani, A; Marbán, E; Periasamy, M
2001-07-20
Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.
Kattanek, Maria; Richardson, Kenneth C.; Hafez, Hafez Mohamed; Plendl, Johanna; Hünigen, Hana
2017-01-01
In this study the macroscopic and microscopic structure of the heart of a fast growing, meat-type turkey line (British United turkeys BUT Big 6) and a wild-type turkey line (Canadian Wild turkey) were compared. At 8 and 16 weeks of age, 10 birds of each genotype and sex were sampled. The body mass and heart mass of the meat-type turkey both increased at a faster rate than those of the wild-type turkey. However in both turkey lines, the relative heart mass decreased slightly with age, the decrease was statistically significant only in the male turkeys. Furthermore meat-type turkeys had a significantly (p < 0.01) lower relative heart mass and relative thickness of the left ventricle compared to the wild-type turkeys of the same age. The wild-type turkeys showed no significant change in the size of cardiomyocytes (cross sectional area and diameter) from 8 weeks to 16 weeks. In contrast, the size of cardiomyocytes increased significantly (p < 0.001) with age in the meat-type turkeys. The number of capillaries in the left ventricular wall increased significantly (p < 0.001) in wild-type turkeys from 2351 per mm2 at the age of 8 weeks to 2843 per mm2 at 16 weeks. However, in the meat-type turkeys there were no significant changes, capillary numbers being 2989 per mm2 at age 8 weeks and 2915 per mm2 at age 16 weeks. Correspondingly the area occupied by capillaries in the myocardium increased in wild-type turkeys from 8.59% at the age of 8 weeks to 9.15% at 16 weeks, whereas in meat-type turkeys this area decreased from 10.4% at 8 weeks to 9.95% at 16 weeks. Our results indicate a mismatch in development between body mass and heart mass and a compromised cardiac capillary density and architecture in the meat-type turkeys in comparison to the wild-type turkeys. PMID:28118415
Cowie, Martin R; Woehrle, Holger; Wegscheider, Karl; Vettorazzi, Eik; Lezius, Susanne; Koenig, Wolfgang; Weidemann, Frank; Smith, Gillian; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita K; Somers, Virend K; Zannad, Faiez; Teschler, Helmut
2018-03-01
The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers. In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months. In secondary analyses, data for patients with baseline and 12-month values were evaluated; 312 patients participated in the substudy. The primary endpoint, change in echocardiographically determined left ventricular ejection fraction from baseline to 12 months, did not differ significantly between the ASV and the control groups. There were also no significant between-group differences for changes in left ventricular dimensions, wall thickness, diastolic function or right ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in small patient numbers). Plasma N-terminal pro B-type natriuretic peptide concentration decreased in both groups, and values were similar at 12 months. There were no significant between-group differences in changes in cardiac, renal and systemic inflammation biomarkers. In patients with systolic heart failure and CSA, addition of ASV to guideline-based medical management had no statistically significant effect on cardiac structure and function, or on cardiac biomarkers, renal function and systemic inflammation over 12 months. The increased cardiovascular mortality reported in SERVE-HF may not be related to adverse remodelling or worsening heart failure. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.
Wang, Wei; Li, Jianbin; Zhang, Yingjie; Shao, Qian; Xu, Min; Guo, Bing; Shang, Dongping
2016-01-01
To investigate the correlation of gross tumor volume (GTV) motion with the structure of interest (SOI) motion and volume variation for middle and distal esophageal cancers using four-dimensional computed tomography (4DCT). Thirty-three patients with middle or distal esophageal carcinoma underwent 4DCT simulation scan during free breathing. All image sets were registered with 0% phase, and the GTV, apex of diaphragm, lung, and heart were delineated on each phase of the 4DCT data. The position of GTV and SOI was identified in all 4DCT phases, and the volume of lung and heart was also achieved. The phase relationship between the GTV and SOI was estimated through Pearson's correlation test. The mean peak-to-peak displacement of all primary tumors in the lateral (LR), anteroposterior (AP), and superoinferior (SI) directions was 0.13 cm, 0.20 cm, and 0.30 cm, respectively. The SI peak-to-peak motion of the GTV was defined as the greatest magnitude of motion. The displacement of GTV correlated well with heart in three dimensions and significantly associated with bilateral lung in LR and SI directions. A significant correlation was found between the GTV and apex of the diaphragm in SI direction (r left=0.918 and r right=0.928). A significant inverse correlation was found between GTV motion and varying lung volume, but the correlation was not significant with heart (r LR=-0.530, r AP=-0.531, and r SI=-0.588) during respiratory cycle. For middle and distal esophageal cancers, GTV should expand asymmetric internal margins. The primary tumor motion has quite good correlation with diaphragm, heart, and lung.
[Combined heart-kidney transplantation in Mexic].
Careaga-Reyna, Guillermo; Zetina-Tun, Hugo Jesús; Lezama-Urtecho, Carlos Alberto; Hernández-Domínguez, José Mariano; Santos-Caballero, Marlene
In our country, heart and kidney transplantation is a novel option for treatment of combined terminal heart and kidney failure. This program began in 2012 for selected patients with documented terminal heart failure and structural kidney damage with renal failure. Description of cases: Between January 1, 2012 and April 30, 2016, we made 92 orthotopic heart transplantations. In five of these cases the heart transplantation was combined with kidney transplantation. There were three male and two female patients with a mean age 25.6 ± 5.2 years (range, 17-29). The patients improved their renal function and the heart transplantation was successful with an improved quality of life. One patient died from abdominal sepsis. The other patients are doing well. The combined heart-kidney transplantation is a safe and efficient procedure for patients with structural kidney and heart damage as a cause of terminal failure.
Bahramali, Ehsan; Rajabi, Mona; Jamshidi, Javad; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar
2016-02-09
To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Case control study. An Iranian referral university hospital. 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Everitt, Ian K; Gerardin, Jennifer F; Rodriguez, Fred H; Book, Wendy M
2017-05-01
The transition and transfer from pediatric to adult care is becoming increasingly important as improvements in the diagnosis and management of congenital heart disease allow patients to live longer. Transition is a complex and continuous process that requires careful planning. Inadequate transition has adverse effects on patients, their families and healthcare delivery systems. Currently, significant gaps exist in patient care as adolescents transfer to adult care and there are little data to drive the informed management of transition and transfer of care in adolescent congenital heart disease patients. Appropriate congenital heart disease care has been shown to decrease mortality in the adult population. This paper reviews the transition and transfer of care processes and outlines current congenital heart disease specific guidelines in the United States and compares these recommendations to Canadian and European guidelines. It then reviews perceived and real barriers to successful transition and identifies predictors of success during transfer to adult congenital heart disease care. Lastly, it explores how disease-specific markers of outcomes and quality indicators are being utilized to guide transition and transfer of care in other chronic childhood illnesses, and identifies existing knowledge gaps and structural impediments to improving the management of transition and transfer among congenital heart disease patients. © 2017 Wiley Periodicals, Inc.
Kochegarov, Andrei; Moses-Arms, Ashley; Lemanski, Larry F
2015-08-01
A specific human fetal heart RNA has been discovered, which has the ability to induce myocardial cell formation from mouse embryonic and human-induced pluripotent stem cells in culture. In this study, commercially obtained RNA from human fetal heart was cloned, sequenced, and synthesized using standard laboratory approaches. Molecular analyses of the specific fetal cardiac-inducing RNA (CIR), revealed that it is a fragment of N-sulfoglucosaminesulfohydrolase and the caspase recruitment domain family member 14 precursor. Stem cells transfected with CIRs often form into spindle-shaped cells characteristic of cardiomyocytes,and express the cardiac-specific contractile protein marker, troponin-T, in addition to tropomyosin and α-actinin as detected by immunohistochemical staining. Expression of these contractile proteins showed organization into sarcomeric myofibrils characteristic of striated cardiac muscle cells. Computer analyses of the RNA secondary structures of the active CIR show significant similarities to a RNA from salamander or myofibril-inducing RNA (MIR), which also promotes non-muscle cells to differentiate into cardiac muscle. Thus, these two RNAs, salamander MIR and the newly discovered human-cloned CIR reported here, appear to have evolutionarily conserved secondary structures suggesting that both play major roles in vertebrate heart development and, particularly, in the differentiation of cardiomyocytes from non-muscle cells during development.
Structure and function of the hearts of lizards and snakes.
Jensen, Bjarke; Moorman, Antoon F M; Wang, Tobias
2014-05-01
With approximately 7000 species, snakes and lizards, collectively known as squamates, are by far the most species-rich group of reptiles. It was from reptile-like ancestors that mammals and birds evolved and squamates can be viewed as phylogenetically positioned between them and fishes. Hence, their hearts have been studied for more than a century yielding insights into the group itself and into the independent evolution of the fully divided four-chambered hearts of mammals and birds. Structurally the heart is complex and debates persist on rudimentary issues such as identifying structures critical to understanding ventricle function. In seeking to resolve these controversies we have generated three-dimensional (3D) models in portable digital format (pdf) of the anaconda and anole lizard hearts ('typical' squamate hearts) and the uniquely specialized python heart with comprehensive annotations of structures and cavities. We review the anatomy and physiology of squamate hearts in general and emphasize the unique features of pythonid and varanid lizard hearts that endow them with mammal-like blood pressures. Excluding pythons and varanid lizards it is concluded that the squamate heart has a highly consistent design including a disproportionately large right side (systemic venous) probably due to prevailing pulmonary bypass (intraventricular shunting). Unfortunately, investigations on rudimentary features are sparse. We therefore point out gaps in our knowledge, such as the size and functional importance of the coronary vasculature and of the first cardiac chamber, the sinus venosus, and highlight areas with implications for vertebrate cardiac evolution. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.
Khara, M R; Pavlovych, S I; Mykhaĭliuk, V M
2013-01-01
In experiments on sexually mature rats we studied specific cholinergic regulations of the heart and the degree of its structural damage in hypothyroidism, depending on gender and hormone-productive activity of the gonads. Hypothyroidism in sexually mature males and females was modelled with mercazolil intragastric administration (75 mg/kg) daily during 15 days. We also studied the intensity of bradycardia, which occurred in response to electrical stimulation of vagus nerve and intravenous acetylcholine administration. The degree of structural heart damage was assessed by the percentage of damaged cardiomyocytes in the ventricles of myocardium. It was found that one of the mechanisms of bradycardia in merkazolil-induced hypothyroidism is an increase of the sensitivity of sinus node cholinergic receptors and release of more quanta of acetylcholine from stimulated nerves vagus endings, what was more intense in females. The intensity of bradycardia in hypothyroidism was more significant in gonadectomized animals than in individuals with preserved gonads. The mechanisms of its occurrence in males consist of release of greater amount of acetylcholine from the endings of the nerves vagus, and in females it was the result of significant increase of the sensitivity of sinus node cholinergic receptors. Regardless of the gonads activity, structural damage of the myocardium in merkazolil-induced hypothyroidism was more intensive in female rats.
Berg, Gregory D; Wadhwa, Sandeep; Johnson, Alan E
2004-10-01
To investigate the utilization and financial outcomes of a telephonic nursing disease-management program for elderly patients with heart failure. A 1-year concurrent matched-cohort study employing propensity score matching. Medicare+Choice recipients residing in Ohio, Kentucky, and Indiana. A total of 533 program participants aged 65 and older matched to nonparticipants. Disease-management heart failure program employing a structured, evidence-based, telephonic nursing intervention designed to provide patient education, counseling, and monitoring services. Medical service utilization, including hospitalizations, emergency department visits, medical doctor visits, skilled nursing facility (SNF) days, selected clinical indicators, and financial effect. The intervention group had considerably and significantly lower rates of acute service utilization than the control group, including 23% fewer hospitalizations, 26% fewer inpatient bed days, 22% fewer emergency department visits, 44% fewer heart failure hospitalizations, 70% fewer 30-day readmissions, and 45% fewer SNF bed days. Claims costs were 1,792 dollars per person lower in the intervention group than in the control group (inclusive of intervention costs), and the return on investment was calculated to be 2.31. The study demonstrates that a commercially delivered heart failure disease-management program significantly reduced hospitalizations, emergency department visits, and SNF days. The intervention group had 17% lower costs than the control group; when intervention costs were included, the intervention group had 10% lower costs.
Application of the health belief model in promotion of self-care in heart failure patients.
Baghianimoghadam, Mohammad Hosein; Shogafard, Golamreza; Sanati, Hamid Reza; Baghianimoghadam, Behnam; Mazloomy, Seyed Saeed; Askarshahi, Mohsen
2013-01-01
Heart failure (HF) is a condition due to a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body's needs. In developing countries, around 2% of adults suffer from heart failure, but in people over the age of 65, this rate increases to 6-10%. In Iran, around 3.3% of adults suffer from heart failure. The Health Belief Model (HBM) is one of the most widely used models in public health theoretical framework. This was a cohort experimental study, in which education as intervention factor was presented to case group. 180 Heart failure patients were randomly selected from patients who were referred to the Shahid Rajaee center of Heart Research in Tehran and allocated to two groups (90 patients in the case group and 90 in the control group). HBM was used to compare health behaviors. The questionnaire included 69 questions. All data were collected before and 2 months after intervention. About 38% of participants don't know what, the heart failure is and 43% don't know that using the salt is not suitable for them. More than 40% of participants didn't weigh any time their selves. There was significant differences between the mean grades score of variables (perceived susceptibility, perceived threat, knowledge, Perceived benefits, Perceived severity, self-efficacy Perceived barriers, cues to action, self- behavior) in the case and control groups after intervention that was not significant before it. Based on our study and also many other studies, HBM has the potential to be used as a tool to establish educational programs for individuals and communities. Therefore, this model can be used effectively to prevent different diseases and their complications including heart failure. © 2013 Tehran University of Medical Sciences. All rights reserved.
Oxidative Stress in Dilated Cardiomyopathy Caused by MYBPC3 Mutation
Lynch, Thomas L.; Sivaguru, Mayandi; Velayutham, Murugesan; Cardounel, Arturo J.; Michels, Michelle; Barefield, David; Govindan, Suresh; dos Remedios, Cristobal; van der Velden, Jolanda; Sadayappan, Sakthivel
2015-01-01
Cardiomyopathies can result from mutations in genes encoding sarcomere proteins including MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). However, whether oxidative stress is augmented due to contractile dysfunction and cardiomyocyte damage in MYBPC3-mutated cardiomyopathies has not been elucidated. To determine whether oxidative stress markers were elevated in MYBPC3-mutated cardiomyopathies, a previously characterized 3-month-old mouse model of dilated cardiomyopathy (DCM) expressing a homozygous MYBPC3 mutation (cMyBP-C(t/t)) was used, compared to wild-type (WT) mice. Echocardiography confirmed decreased percentage of fractional shortening in DCM versus WT hearts. Histopathological analysis indicated a significant increase in myocardial disarray and fibrosis while the second harmonic generation imaging revealed disorganized sarcomeric structure and myocyte damage in DCM hearts when compared to WT hearts. Intriguingly, DCM mouse heart homogenates had decreased glutathione (GSH/GSSG) ratio and increased protein carbonyl and lipid malondialdehyde content compared to WT heart homogenates, consistent with elevated oxidative stress. Importantly, a similar result was observed in human cardiomyopathy heart homogenate samples. These results were further supported by reduced signals for mitochondrial semiquinone radicals and Fe-S clusters in DCM mouse hearts measured using electron paramagnetic resonance spectroscopy. In conclusion, we demonstrate elevated oxidative stress in MYPBC3-mutated DCM mice, which may exacerbate the development of heart failure. PMID:26508994
Model-specific selection of molecular targets for heart failure gene therapy
Katz, Michael G.; Fargnoli, Anthony S.; Tomasulo, Catherine E.; Pritchette, Louella A.; Bridges, Charles R.
2013-01-01
Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca2+ handling proteins and angiogenesis in the most common extrinsic models of HF. PMID:21954055
Jana, Soumen; Lerman, Amir
2015-12-01
Heart valve tissue engineering could be a possible solution for the limitations of mechanical and biological prostheses, which are commonly used for heart valve replacement. In tissue engineering, cells are seeded into a 3-dimensional platform, termed the scaffold, to make the engineered tissue construct. However, mimicking the mechanical and spatial heterogeneity of a heart valve structure in a fabricated scaffold with uniform cell distribution is daunting when approached conventionally. Bioprinting is an emerging technique that can produce biological products containing matrix and cells, together or separately with morphological, structural and mechanical diversity. This advance increases the possibility of fabricating the structure of a heart valve in vitro and using it as a functional tissue construct for implantation. This review describes the use of bioprinting technology in heart valve tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.
Sharma, Vivek Kumar; Subramanian, Senthil Kumar; Radhakrishnan, Krishnakumar; Rajendran, Rajathi; Ravindran, Balasubramanian Sulur; Arunachalam, Vinayathan
2017-05-01
Physical inactivity contributes to many health issues. The WHO-recommended physical activity for adolescents encompasses aerobic, resistance, and bone strengthening exercises aimed at achieving health-related physical fitness. Heart rate variability (HRV) and maximal aerobic capacity (VO2max) are considered as noninvasive measures of cardiovascular health. The objective of this study is to compare the effect of structured and unstructured physical training on maximal aerobic capacity and HRV among adolescents. We designed a single blinded, parallel, randomized active-controlled trial (Registration No. CTRI/2013/08/003897) to compare the physiological effects of 6 months of globally recommended structured physical activity (SPA), with that of unstructured physical activity (USPA) in healthy school-going adolescents. We recruited 439 healthy student volunteers (boys: 250, girls: 189) in the age group of 12-17 years. Randomization across the groups was done using age and gender stratified randomization method, and the participants were divided into two groups: SPA (n=219, boys: 117, girls: 102) and USPA (n=220, boys: 119, girls: 101). Depending on their training status and gender the participants in both SPA and USPA groups were further subdivided into the following four sub-groups: SPA athlete boys (n=22) and girls (n=17), SPA nonathlete boys (n=95) and girls (n=85), USPA athlete boys (n=23) and girls (n=17), and USPA nonathlete boys (n=96) and girls (n=84). We recorded HRV, body fat%, and VO2 max using Rockport Walk Fitness test before and after the intervention. Maximum aerobic capacity and heart rate variability increased significantly while heart rate, systolic blood pressure, diastolic blood pressure, and body fat percentage decreased significantly after both SPA and USPA intervention. However, the improvement was more in SPA as compared to USPA. SPA is more beneficial for improving cardiorespiratory fitness, HRV, and reducing body fat percentage in terms of magnitude than USPA in adolescent individuals irrespective of their gender and sports activities.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Prabhakar, Ramachandran; Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi; Department of Radiology, All India Institute of Medical Sciences, New Delhi
Setup error plays a significant role in the final treatment outcome in radiotherapy. The effect of setup error on the planning target volume (PTV) and surrounding critical structures has been studied and the maximum allowed tolerance in setup error with minimal complications to the surrounding critical structure and acceptable tumor control probability is determined. Twelve patients were selected for this study after breast conservation surgery, wherein 8 patients were right-sided and 4 were left-sided breast. Tangential fields were placed on the 3-dimensional-computed tomography (3D-CT) dataset by isocentric technique and the dose to the PTV, ipsilateral lung (IL), contralateral lung (CLL),more » contralateral breast (CLB), heart, and liver were then computed from dose-volume histograms (DVHs). The planning isocenter was shifted for 3 and 10 mm in all 3 directions (X, Y, Z) to simulate the setup error encountered during treatment. Dosimetric studies were performed for each patient for PTV according to ICRU 50 guidelines: mean doses to PTV, IL, CLL, heart, CLB, liver, and percentage of lung volume that received a dose of 20 Gy or more (V20); percentage of heart volume that received a dose of 30 Gy or more (V30); and volume of liver that received a dose of 50 Gy or more (V50) were calculated for all of the above-mentioned isocenter shifts and compared to the results with zero isocenter shift. Simulation of different isocenter shifts in all 3 directions showed that the isocentric shifts along the posterior direction had a very significant effect on the dose to the heart, IL, CLL, and CLB, which was followed by the lateral direction. The setup error in isocenter should be strictly kept below 3 mm. The study shows that isocenter verification in the case of tangential fields should be performed to reduce future complications to adjacent normal tissues.« less
2014-01-01
Background Research-informed fetal monitoring guidelines recommend intermittent auscultation (IA) for fetal heart monitoring for low-risk women. However, the use of cardiotocography (CTG) continues to dominate many institutional maternity settings. Methods A mixed methods intervention study with before and after measurement was undertaken in one secondary level health service to facilitate the implementation of an initiative to encourage the use of IA. The intervention initiative was a decision-making framework called Intelligent Structured Intermittent Auscultation (ISIA) introduced through an education session. Results Following the intervention, medical records review revealed an increase in the use of IA during labour represented by a relative change of 12%, with improved documentation of clinical findings from assessments, and a significant reduction in the risk of receiving an admission CTG (RR 0.75, 95% CI, 0.60 – 0.95, p = 0.016). Conclusion The ISIA informed decision-making framework transformed the practice of IA and provided a mechanism for knowledge translation that enabled midwives to implement evidence-based fetal heart monitoring for low risk women. PMID:24884597
Prenatal diagnosis of left isomerism with normal heart: a case report
De Paola, Nico; Ermito, Santina; Nahom, Antonella; Dinatale, Angela; Pappalardo, Elisa Maria; Carrara, Sabina; Cavaliere, Alessandro; Brizzi, Cristiana
2009-01-01
Objective: Left isomerism, also called polysplenia, is a laterality disturbance associated with with paired leftsidedness viscera and multiple small spleens. Left isomerism, heart congenital abnormalities and gastrointestinal malformation are strongly associated. Methods: We present a case of prenatal diagnosis of left isomerism in a fetus with a structurally normal heart. Conclusion: Left isomerism syndrone may coesist with a structurally normal heart. If prenatal left isomerism is suspected, even in presence of a normal heart, is mandatory to esclude sign of gastrointestinal abnormalities, as late poly hy dramnios, and cardiac rhytm disturbance during the pregnancy and neonatal age. PMID:22439041
Fetal Echocardiography/Your Unborn Baby's Heart
... heart for the doctor to evaluate. The sound waves can also detect blood flow throughout the baby's heart. This enables the doctor to evaluate the structure and function of the fetal heart. Who needs one? Fetal ...
Heshmati, Elaheh; Shirpoor, Alireza; Kheradmand, Fatemeh; Alizadeh, Mohammad; Gharalari, Farzaneh Hosseini
2018-01-01
Association between chronic alcohol intake and cardiac abnormality is well known; however, the precise underlying molecular mediators involved in ethanol-induced heart abnormalities remain elusive. This study investigated the effect of chronic ethanol exposure on calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) gene expression and monoamine oxidase (MAO) levels and histological changes in rat heart. It was also planned to find out whether Zingiber officinale (ginger) extract mitigated the abnormalities induced by ethanol in rat heart. Male wistar rats were divided into three groups of eight animals each: control, ethanol, and ginger extract treated-ethanol (GETE) groups. After 6 weeks of treatment, the results revealed a significant increase in CaMKIIδtotal and isoforms δ2 and δ3 of CaMKIIδ gene expression as well as a significant decrease in the MAO levels in the ethanol group compared to that in the control group. Moreover, compared to the control group, the ethanol group showed histological changes, such as fibrosis, heart muscle cells proliferation, myocyte hypertrophy, vacuolization, and focal lymphocytic infiltration. Consumption of ginger extract along with ethanol ameliorated CaMKIIδtotal. In addition, compared to the ethanol group, isoforms gene expression changed and increased the reduced MAO levels and mitigated heart structural changes. These findings indicate that ethanol-induced heart abnormalities may, in part, be associated with Ca 2+ homeostasis changes mediated by overexpression of CaMKIIδ gene and the decrease of MAO levels and that these effects can be alleviated by using ginger extract as an antioxidant and anti-inflammatory agent.
Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart.
Zhang, Hongmei; Dong, Yan; Su, Qing
2017-02-01
In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.
Brossard-Racine, M; du Plessis, A J; Vezina, G; Robertson, R; Bulas, D; Evangelou, I E; Donofrio, M; Freeman, D; Limperopoulos, C
2014-08-01
Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively. Our primary objective was to determine the prevalence and spectrum of brain abnormalities detected on conventional clinical MR imaging in fetuses with complex congenital heart disease and, second, to compare the congenital heart disease cohort with a control group of fetuses from healthy pregnancies. We prospectively recruited pregnant women with a confirmed fetal congenital heart disease diagnosis and healthy volunteers with normal fetal echocardiogram findings who underwent a fetal MR imaging between 18 and 39 weeks gestational age. A total of 338 fetuses (194 controls; 144 with congenital heart disease) were studied at a mean gestational age of 30.61 ± 4.67 weeks. Brain abnormalities were present in 23% of the congenital heart disease group compared with 1.5% in the control group (P < .001). The most common abnormalities in the congenital heart disease group were mild unilateral ventriculomegaly in 12/33 (36.4%) and increased extra-axial spaces in 10/33 (30.3%). Subgroup analyses comparing the type and frequency of brain abnormalities based on cardiac physiology did not reveal significant associations, suggesting that the brain abnormalities were not limited to those with the most severe congenital heart disease. This is the first large prospective study reporting conventional MR imaging findings in fetuses with congenital heart disease. Our results suggest that brain abnormalities are prevalent but relatively mild antenatally in fetuses with congenital heart disease. The long-term predictive value of these findings awaits further study. © 2014 by American Journal of Neuroradiology.
Heart Transplant in Patients with Predominantly Rheumatic Valvular Heart Disease.
Rosa, Vitor E E; Lopes, Antonio S S A; Accorsi, Tarso A D; Fernandes, Joao Ricardo C; Spina, Guilherme S; Sampaio, Roney O; Bacal, Fernando; Tarasoutchi, Flavio
2015-09-01
International records indicate that only 2.6% of patients with heart transplants have valvular heart disease. The study aim was to evaluate the epidemiological and clinical profile of patients with valvular heart disease undergoing heart transplantation. Between 1985 and 2013, a total of 569 heart transplants was performed at the authors' institution. Twenty patients (13 men, seven women; mean age 39.5 +/- 15.2 years) underwent heart transplant due to structural (primary) valvular disease. Analyses were made of the patients' clinical profile, laboratory data, echocardiographic and histopathological data, and mortality and rejection. Of the patients, 18 (90%) had a rheumatic etiology, with 85% having undergone previous valve surgery (45% had one or more operations), and 95% with a normal functioning valve prosthesis at the time of transplantation. Atrial fibrillation was present in seven patients (35%), while nine (45%) were in NYHA functional class IV and eight (40%) in class III. The indication for cardiac transplantation was refractory heart failure in seven patients (35%) and persistent NYHA class III/IV in ten (50%). The mean left ventricular ejection fraction (LVEF) was 26.6 +/- 7.9%. The one-year mortality was 20%. Histological examination of the recipients' hearts showed five (27.7%) to have reactivated rheumatic myocarditis without prior diagnosis at the time of transplantation. Univariate analysis showed that age, gender, LVEF, rheumatic activity and rejection were not associated with mortality at one year. Among the present patient cohort, rheumatic heart disease was the leading cause of heart transplantation, and a significant proportion of these patients had reactivated myocarditis diagnosed in the histological analyses. Thus, it appears valid to investigate the existence of rheumatic activity, especially in valvular cardiomyopathy with severe systolic dysfunction before transplantation.
Does the visibility of a congenital anomaly affect maternal-infant attachment levels?
Boztepe, Handan; Ay, Ayşe; Kerimoğlu Yıldız, Gizem; Çınar, Sevil
2016-10-01
To determine whether congenital anomaly visibility affects maternal-infant attachment levels. The study population consisted of mothers who had infants with cleft lip/palate or congenital heart anomalies who were receiving treatment in a university hospital. The data were collected using the Structured Questionnaire Form and the Maternal Attachment Inventory. Statistically significant differences in maternal-infant attachment levels were observed between infants with cleft lips/palates and healthy infants and between infants with congenital heart anomalies and healthy infants. It is important to apply appropriate nursing interventions for these mothers during the postpartum period. © 2016, Wiley Periodicals, Inc.
Ahir, Bhavesh K; Pratten, Margaret K
2014-01-01
Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.
Physiological Implications of Myocardial Scar Structure
Richardson, WJ; Clarke, SA; Quinn, TA; Holmes, JW
2016-01-01
Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following an MI, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction. PMID:26426470
Cano-Martínez, Agustina; Vargas-González, Alvaro; Guarner-Lans, Verónica; Prado-Zayago, Esteban; León-Oleda, Martha; Nieto-Lima, Betzabé
2010-01-01
"In the present study we evaluated the effect of partial ventricular amputation (PVA) in the heart of the adult urodele amphibian (Ambystoma mexicanum) in vivo on spontaneous heart contractile activity recorded in vitro in association to the structural recovery at one, five, 30 and 90 days after injury. One day after PVA, ventricular-tension (VT) (16 ± 3%), atrium-tension (AT) (46 ± 4%) and heart rate (HR) (58+10%) resulted lower in comparison to control hearts. On days five, 30 and 90 after damage, values achieved a 61 ± 5, 93 ± 3, and 98 ± 5% (VT), 60 ± 4, 96 ± 3 and 99 ± 5% (AT) and 74 ± 5, 84 ± 10 and 95 ± 10% (HR) of the control values, respectively. Associated to contractile activity recovery we corroborated a gradual tissue restoration by cardiomyocyte proliferation. Our results represent the first quantitative evidence about the recovery of heart of A. mexicanum restores its functional capacity concomitantly to the structural recovery of the myocardium by proliferation of cardiomyocytes after PVA. These properties make the heart of A. mexicanum a potential model to study the mechanisms underlying heart regeneration in adult vertebrates in vivo.
Equine Cardiovascular Therapeutics.
Sleeper, Meg M
2017-04-01
Heart disease can be defined as any abnormality of the heart whether it is a cardiac dysrhythmia or structural heart disease, either congenital or acquired. Heart failure occurs when a cardiac abnormality results in the inability of the heart to pump enough blood to meet the body's needs. Heart disease can be present without leading to heart failure. Heart failure, however, is a consequence of heart disease. There are 4 main areas where the clinician can intervene to improve cardiac output with heart failure: preload, afterload, myocardial contractility, and heart rate. Copyright © 2016 Elsevier Inc. All rights reserved.
Gomez, Juan F.; Cardona, Karen; Martinez, Laura; Saiz, Javier; Trenor, Beatriz
2014-01-01
Background Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure. Objective In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations. Methods The electrical activity of human transmural ventricular tissue (5 cm×5 cm) was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW) for reentry was evaluated following cross-field stimulation. Results No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components. Conclusion Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity. PMID:25054335
Shepherd, Emma; Stuart, Graham; Martin, Rob; Walsh, Mark A
2015-06-01
SelectSecure™ pacing leads (Medtronic Inc) are increasingly being used in pediatric patients and adults with structural congenital heart disease. The 4Fr lead is ideal for patients who may require lifelong pacing and can be advantageous for patients with complex anatomy. The purpose of this study was to compare the extraction of SelectSecure leads with conventional (stylette-driven) pacing leads in patients with structural congenital heart disease and congenital atrioventricular block. The data on lead extractions from pediatric and adult congenital heart disease (ACHD) patients from August 2004 to July 2014 at Bristol Royal Hospital for Children and the Bristol Heart Institute were reviewed. Multivariable regression analysis was used to determine whether conventional pacing leads were associated with a more difficult extraction process. A total of 57 patients underwent pacemaker lead extractions (22 SelectSecure, 35 conventional). No deaths occurred. Mean age at the time of extraction was 17.6 ± 10.5 years, mean weight was 47 ± 18 kg, and mean lead age was 5.6 ± 2.6 years (range 1-11 years). Complex extraction (partial extraction/femoral extraction) was more common in patients with conventional pacing leads at univariate (P < .01) and multivariate (P = .04) levels. Lead age was also a significant predictor of complex extraction (P < .01). SelectSecure leads can be successfully extracted using techniques that are used for conventional pacing leads. They are less likely to be partially extracted and are less likely to require extraction using a femoral approach compared with conventional pacing leads. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Multidsciplinary heart failure management and end of life care.
Ryder, Mary; Beattie, James M; O'Hanlon, Rory; McDonald, Kenneth
2011-12-01
There has been much improvement in the treatment of heart failure over the past decade through the implementation of a multidisciplinary team approach to disease management focused on optimizing medication, the application of device-based therapy, surgical intervention and in promoting the education of patients and carers in self-management. This multidisciplinary strategy has now been extended to try and improve the care of those with advanced heart failure in the latter phases of the disease trajectory nearing the end of their lives. A growing consensus has emerged in the literature that confirms the need to extend multidisciplinary management beyond the early targets of reducing heart failure-related mortality and morbidity to address the significant care needs of those who decline due to the often inexorable progression of this syndrome. Multidisciplinary management facilitates the development of a comprehensive care plan that is specifically tailored to accommodate the requirements of individual patients and their families and fosters a collaborative approach to care to optimize symptom management, avoid potential treatments conflicts, and to fulfil their supportive care needs. Partnership working between the three principal clinical disciplines of cardiology, specialist palliative care and general practice is central to this process and promotes coordinated care across hospital, hospice and community-based services. Advanced heart failure management has improved over time; however, the incorporation of a multidisciplinary care model appears to offer significant promise in dealing with complex care needs of heart failure patients towards the end of life. Delivery of this practice requires the development of bespoke care structures that are relevant to the spectrum of healthcare service environments.
Quantification and comparison of the mechanical properties of four human cardiac valves.
Pham, Thuy; Sulejmani, Fatiesa; Shin, Erica; Wang, Di; Sun, Wei
2017-05-01
Although having the same ability to permit unidirectional flow within the heart, the four main valves-the mitral valve (MV), aortic (AV), tricuspid (TV) and pulmonary (PV) valves-experience different loading conditions; thus, they exhibit different structural integrity from one another. Most research on heart valve mechanics have been conducted mainly on MV and AV or an individual valve, but none quantify and compare the mechanical and structural properties among the four valves from the same aged patient population whose death was unrelated to cardiovascular disease. A total of 114 valve leaflet samples were excised from 12 human cadavers whose death was unrelated to cardiovascular disease (70.1±3.7years old). Tissue mechanical and structural properties were characterized by planar biaxial mechanical testing and histological methods. The experimental data were then fitted with a Fung-type constitutive model. The four valves differed substantially in thickness, degree of anisotropy, and stiffness. The leaflets of the left heart (the AV leaflets and the anterior mitral leaflets, AML) were significantly stiffer and less compliant than their counterparts in the right heart. TV leaflets were the most extensible and isotropic, while AML and AV leaflets were the least extensible and the most anisotropic. Age plays a significant role in the reduction of leaflet stiffness and extensibility with nearly straightened collagen fibers observed in the leaflet samples from elderly groups (65years and older). Results from 114 human leaflet samples not only provided a baseline quantification of the mechanical properties of aged human cardiac valves, but also offered a better understanding of the age-dependent differences among the four valves. It is hoped that the experimental data collected and the associated constitutive models in this study can facilitate future studies of valve diseases, treatments and the development of interventional devices. Most research on heart valve mechanics have been conducted mainly on mitral and aortic valves or an individual valve, but none quantify and compare the mechanical and structural properties among the four valves from the same relatively healthy elderly patient population. In this study, the mechanical and microstructural properties of 114 leaflets of aortic, mitral, pulmonary and tricuspid valves from 12 human cadaver hearts were mechanically tested, analyzed and compared. Our results not only provided a baseline quantification of the mechanical properties of aged human valves, but a age range between patients (51-87years) also offers a better understanding of the age-dependent differences among the four valves. It is hoped that the obtained experimental data and associated constitutive parameters can facilitate studies of valve diseases, treatments and the development of interventional devices. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Azevedo, Luciene Ferreira; Perlingeiro, Patricia; Hachul, Denise Tessariol; Gomes-Santos, Igor Lucas; Tsutsui, Jeane Mike; Negrao, Carlos Eduardo; De Matos, Luciana D N J
2016-01-01
Different season trainings may influence autonomic and non-autonomic cardiac control of heart rate and provokes specific adaptations on heart's structure in athletes. We investigated the influence of transition training (TT) and competitive training (CT) on resting heart rate, its mechanisms of control, spontaneous baroreflex sensitivity (BRS) and relationships between heart rate mechanisms and cardiac structure in professional cyclists (N = 10). Heart rate (ECG) and arterial blood pressure (Pulse Tonometry) were recorded continuously. Autonomic blockade was performed (atropine-0.04 mg.kg-1; esmolol-500 μg.kg-1 = 0.5 mg). Vagal effect, intrinsic heart rate, parasympathetic (n) and sympathetic (m) modulations, autonomic influence, autonomic balance and BRS were calculated. Plasma norepinephrine (high-pressure liquid chromatography) and cardiac structure (echocardiography) were evaluated. Resting heart rate was similar in TT and CT. However, vagal effect, intrinsic heart rate, autonomic influence and parasympathetic modulation (higher n value) decreased in CT (P≤0.05). Sympathetic modulation was similar in both trainings. The autonomic balance increased in CT but still showed parasympathetic predominance. Cardiac diameter, septum and posterior wall thickness and left ventricular mass also increased in CT (P<0.05) as well as diastolic function. We observed an inverse correlation between left ventricular diastolic diameter, septum and posterior wall thickness and left ventricular mass with intrinsic heart rate. Blood pressure and BRS were similar in both trainings. Intrinsic heart rate mechanism is predominant over vagal effect during CT, despite similar resting heart rate. Preserved blood pressure levels and BRS during CT are probably due to similar sympathetic modulation in both trainings.
Generation Mechanism of Alternans in Luo-Rudy Model
NASA Astrophysics Data System (ADS)
Kitajima, Hiroyuki; Ioka, Eri; Yazawa, Toru
Electrical alternans is the alternating amplitude from beat to beat in the action potential of the cardiac cell. It has been associated with ventricular arrhythmias in many clinical studies; however, its dynamical mechanisms remain unknown. The reason is that we do not have realistic network models of the heart system. Recently, Yazawa clarified the network structure of the heart and the central nerve system in the crustacean heart. In this study, we construct a simple model of the heart system based on Yazawa’s experimental data. Using this model, we clarify that two parameters (the conductance of sodium ions and free concentration of potassium ions in the extracellular compartment) play the key roles of generating alternans. In particular, we clarify that the inactivation gate of the time-independent potassium channel is the most important parameter. Moreover, interaction between the membrane potential and potassium ionic currents is significant for generating alternate rhythms. This result indicates that if the muscle cell has problems such as channelopathies, there is great risk of generating alternans.
Luckraz, Heyman; Norell, Michael; Buch, Mamta; James, Rachael; Cooper, Graham
2015-10-01
The decision-making process in the management of patients with ischaemic heart disease has historically been the responsibility of the cardiologist and encompasses medical management, percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Currently, there is significant geographical variability in the PCI:CABG ratio. There are now emerging recommendations that this decision-making process should be carried out through a multidisciplinary approach, namely the Heart Team. This work was carried out on behalf of The British Cardiovascular Society (BCS), Society for Cardiothoracic Surgery in Great Britain and Ireland (SCTS) and British Cardiovascular Intervention Society (BCIS). This manuscript sets out the principles for the functioning of the Heart Team. This work has been approved by the Executive Committees of BCS/BCIS/SCTS. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Brown, Mark P
2006-01-01
The effect of nursing professionals (i.e., nurse aid/orderly, licensed practical nurse, registered nurse) pay structures and pay levels on hospitals risk-adjusted heart attack outcomes was determined. Operationalizing hospitals' heart attack outcomes as their thirty-day risk-adjusted mortality rates, a positive curvilinear relation is hypothesized between pay dispersion and hospitals' heart attack outcomes, whereas a direct relation is hypothesized between pay level and hospitals' heart attack outcomes. Pay level is also hypothesized as a moderator of the relation between pay dispersion and hospitals' heart attack outcomes. Using a sample of 138 California hospitals, support is not found for either the curvilinear relation between hospitals' nursing professionals pay dispersion and hospitals' heart attack outcomes, or the direct relation between nursing professionals' pay level and hospitals' heart attack outcomes. Support is found for the moderation hypothesis in which nursing professionals' pay level moderates the relation between hospitals' nursing professionals pay dispersion and hospitals' heart attack outcomes. Implications for practice are discussed in light of the study's results.
Functional Strain-Line Pattern in the Human Left Ventricle
NASA Astrophysics Data System (ADS)
Pedrizzetti, Gianni; Kraigher-Krainer, Elisabeth; De Luca, Alessio; Caracciolo, Giuseppe; Mangual, Jan O.; Shah, Amil; Toncelli, Loira; Domenichini, Federico; Tonti, Giovanni; Galanti, Giorgio; Sengupta, Partho P.; Narula, Jagat; Solomon, Scott
2012-07-01
Analysis of deformations in terms of principal directions appears well suited for biological tissues that present an underlying anatomical structure of fiber arrangement. We applied this concept here to study deformation of the beating heart in vivo analyzing 30 subjects that underwent accurate three-dimensional echocardiographic recording of the left ventricle. Results show that strain develops predominantly along the principal direction with a much smaller transversal strain, indicating an underlying anisotropic, one-dimensional contractile activity. The strain-line pattern closely resembles the helical anatomical structure of the heart muscle. These findings demonstrate that cardiac contraction occurs along spatially variable paths and suggest a potential clinical significance of the principal strain concept for the assessment of mechanical cardiac function. The same concept can help in characterizing the relation between functional and anatomical properties of biological tissues, as well as fiber-reinforced engineered materials.
Paravalvular Leak in Structural Heart Disease.
Goel, Kashish; Eleid, Mackram F
2018-03-06
This review will summarize the growing importance of diagnosing and managing paravalvular leak associated with surgical and transcatheter valves. The burden of paravalvular leak is increasing; however, advanced imaging techniques and high degree of clinical suspicion are required for diagnosis and management. The latest data from pivotal clinical trials in the field of transcatheter aortic valve replacement suggest that any paravalvular leak greater than mild was associated with worse clinical outcomes. Percutaneous techniques for paravalvular leak closure are now the preferred approach, and surgical repair is reserved for contraindications and unsuccessful procedures. Recent data from studies evaluating paravalvular leak closure outcomes report a greater than 90% success rate with a significant improvement in patient symptoms. Paravalvular leak is a growing problem in the structural heart disease arena. Percutaneous closure is successful in more than 90% of the procedures with a low complication rate.
Care management for low-risk patients with heart failure: a randomized, controlled trial.
DeBusk, Robert Frank; Miller, Nancy Houston; Parker, Kathleen Marie; Bandura, Albert; Kraemer, Helena Chmura; Cher, Daniel Joseph; West, Jeffrey Alan; Fowler, Michael Bruce; Greenwald, George
2004-10-19
Nurse care management programs for patients with chronic illness have been shown to be safe and effective. To determine whether a telephone-mediated nurse care management program for heart failure reduced the rate of rehospitalization for heart failure and for all causes over a 1-year period. Randomized, controlled trial of usual care with nurse management versus usual care alone in patients hospitalized for heart failure from May 1998 through October 2001. 5 northern California hospitals in a large health maintenance organization. Of 2786 patients screened, 462 met clinical criteria for heart failure and were randomly assigned (228 to intervention and 234 to usual care). Nurse care management provided structured telephone surveillance and treatment for heart failure and coordination of patients' care with primary care physicians. Time to first rehospitalization for heart failure or for any cause and time to a combined end point of first rehospitalization, emergency department visit, or death. At 1 year, half of the patients had been rehospitalized at least once and 11% had died. Only one third of rehospitalizations were for heart failure. The rate of first rehospitalization for heart failure was similar in both groups (proportional hazard, 0.85 [95% CI, 0.46 to 1.57]). The rate of all-cause rehospitalization was similar (proportional hazard, 0.98 [CI, 0.76 to 1.27]). The findings of this study, conducted in a single health care system, may not be generalizable to other health care systems. The overall effect of the intervention was minor. Among patients with heart failure at low risk on the basis of sociodemographic and medical attributes, nurse care management did not statistically significantly reduce rehospitalizations for heart failure or for any cause. Such programs may be less effective for patients at low risk than those at high risk.
Response and adaptation of Beagle dogs to hypergravity
NASA Technical Reports Server (NTRS)
Oyama, J.
1975-01-01
Eight male Beagle dogs, five months old, were centrifuged continuously for three months at progressively increasing loads. Heart rate and deep body temperature were monitored continuously by implant biotelemetry. Initially, centrifuged dogs showed transient decreases in heart rate and body temperature along with changes in their diurnal rhythm patterns. Compared with normal gravity controls, exposed dogs showed a slower growth rate and a reduced amount of body fat. Blood protein, total lipids, cholesterol, calcium, packed cell volume, red blood cell count, and hemoglobin were also decreased significantly. Absolute weights of the leg bones of centrifuged dogs were significantly greater than controls. Photon absorptiometry revealed significant density increases in selective regions of the femur and humerus of centrifuged dogs. In spite of the various changes noted, results from this and other studies affirm the view that dogs can tolerate and adapt to sustained loads as high as 2.5 g without serious impairment of their body structure and function.
Bristow, Michael R; Kao, David P; Breathett, Khadijah K; Altman, Natasha L; Gorcsan, John; Gill, Edward A; Lowes, Brian D; Gilbert, Edward M; Quaife, Robert A; Mann, Douglas L
2017-11-01
Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Nkoke, Clovis; Balti, Eric; Menanga, Alain; Dzudie, Anastase; Lekoubou, Alain; Kingue, Samuel; Kengne, Andre Pascal
2017-01-01
Congenital heart disease (CHD) is a common condition in children in Sub-Saharan Africa (SSA), where it is associated with poor outcomes. Diagnosis of CHD in SSA depends essentially on echocardiography, which is available only in few urban referral centers. Our aim was to assess time changes in the pattern of referral for pediatric echocardiography and the subsequent diagnosis of structural CHD in a major SSA city. All pediatric echocardiography performed between 2004 and 2013 at the echocardiography laboratory of the Yaounde General Hospital were reviewed. The primary indication of the study and the presence of structural CHD were recorded. Between 2004 and 2013, 9,390 echocardiograms were performed and 834 (8.9%) children aged 1 day to 15 years underwent echocardiography at the center, and 227 (27.2%) cases of definite structural CHD were diagnosed, with 123 (54.2%) in boys. The most frequent indications for echocardiography were heart murmurs (40%) and the suspicion of CHD (37.4%). The commonest CHD was ventricular septal defect (VSD) (30%) with tetralogy of Fallot being the most frequent cyanotic heart lesion (5.3%). The proportion of pediatric echocardiography decreased from 13.3% in 2004-2005 to 6.1% in 2012-2013 (P=0.001) but not in a linear fashion (P=0.072 for linear trend).The diagnosis of structural CHD increased from 25.1% in 2004-2005 to 27.1% in 2012-2013. This increase however was non-significant (P=0.523) and did not follow a linear trend (P=0.230). The pattern of referral for pediatric echocardiography at this center has changed over time, but diagnosis of structural CHD has remained the same. Improving access to this diagnostic procedure and subsequent treatment of diagnosed CHD will help improving the outcome of the disease in this setting.
McBride, Kim L.; Pignatelli, Ricardo; Lewin, Mark; Ho, Trang; Fernbach, Susan; Menesses, Andres; Lam, Wilbur; Leal, Suzanne M.; Kaplan, Norman; Schliekelman, Paul; Towbin, Jeffrey A.; Belmont, John W.
2006-01-01
The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71–0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1–6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects. PMID:15690347
Matějková, Adéla; Steiner, Ivo
2014-01-01
Atrial fibrillation (AF), the most common supraventricular tachycardia, has a morphological base, so called remodelation of atrial myocardium, with its abnormal conduction pattern as a consequence. The remodelation regards electrical, contractile, and structural properties. In this pilot study we attempted to find relations between the myocardial morphological (scarring, amyloidosis, left atrial enlargement) and electrophysiological (ECG characteristics of the P-wave) changes in patients with AF. We examined 40 hearts of necropsy patients - 20 with a history of AF and 20 with no history of AF. Grossly, the heart weight and the size of the left atrium (LA) were evaluated. Histologically, 7 standard sites from the atria were examined. In each specimen, the degree of myocardial scarring and of deposition of isolated atrial amyloid (IAA) were assessed. We failed to show any significant difference in the P-wave pattern between patients with and without AF. Morphologically, however, there were several differences - the patients with AF had significantly heavier hearts, larger left atria, more severely scarred myocardium of the LA and the atrial septum, and more severe deposition of IAA in both atria in comparison to the control group of patients with sinus rhythm. The left atrial distribution of both fibrosis and amyloidosis was irregular. In patients with AF the former was most pronounced in the LA ceiling while the latter in the LA anterior wall. The entire series showed more marked amyloidosis in the left than in the right atrium. An interesting finding was the universal absence of IAA in the sinoatrial node. The knowledge of distribution of atrial myocardial structural changes could be utilized by pathologists in taking specimens for histology and also by cardiologists in targeting the radiofrequency ablation therapy.
Qi, Xiangbing; Gui, Wen-Jun; Morlock, Lorraine K.; Wallace, Amy L.; Ahmed, Kamran; Laxman, Sunil; Campeau, Philippe M.; Lee, Brendan H.; Hutson, Susan M.; Tu, Benjamin P.; Williams, Noelle S.; Tambar, Uttam K.; Wynn, R. Max; Chuang, David T.
2013-01-01
The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are elevated in maple syrup urine disease, heart failure, obesity, and type 2 diabetes. BCAA homeostasis is controlled by the mitochondrial branched-chain α-ketoacid dehydrogenase complex (BCKDC), which is negatively regulated by the specific BCKD kinase (BDK). Here, we used structure-based design to develop a BDK inhibitor, (S)-α-chloro-phenylpropionic acid [(S)-CPP]. Crystal structures of the BDK-(S)-CPP complex show that (S)-CPP binds to a unique allosteric site in the N-terminal domain, triggering helix movements in BDK. These conformational changes are communicated to the lipoyl-binding pocket, which nullifies BDK activity by blocking its binding to the BCKDC core. Administration of (S)-CPP to mice leads to the full activation and dephosphorylation of BCKDC with significant reduction in plasma BCAA concentrations. The results buttress the concept of targeting mitochondrial BDK as a pharmacological approach to mitigate BCAA accumulation in metabolic diseases and heart failure. PMID:23716694
Melkani, Girish C.; Bodmer, Rolf; Ocorr, Karen; Bernstein, Sanford I.
2011-01-01
UNC-45 is a UCS (UNC-45/CRO1/She4P) class chaperone necessary for myosin folding and/or accumulation, but its requirement for maintaining cardiac contractility has not been explored. Given the prevalence of myosin mutations in eliciting cardiomyopathy, chaperones like UNC-45 are likely to be equally critical in provoking or modulating myosin-associated cardiomyopathy. Here, we used the Drosophila heart model to examine its role in cardiac physiology, in conjunction with RNAi-mediated gene silencing specifically in the heart in vivo. Analysis of cardiac physiology was carried out using high-speed video recording in conjunction with movement analysis algorithms. unc-45 knockdown resulted in severely compromised cardiac function in adults as evidenced by prolonged diastolic and systolic intervals, and increased incidence of arrhythmias and extreme dilation; the latter was accompanied by a significant reduction in muscle contractility. Structural analysis showed reduced myofibrils, myofibrillar disarray, and greatly decreased cardiac myosin accumulation. Cardiac unc-45 silencing also dramatically reduced life-span. In contrast, third instar larval and young pupal hearts showed mild cardiac abnormalities, as severe cardiac defects only developed during metamorphosis. Furthermore, cardiac unc-45 silencing in the adult heart (after metamorphosis) led to less severe phenotypes. This suggests that UNC-45 is mostly required for myosin accumulation/folding during remodeling of the forming adult heart. The cardiac defects, myosin deficit and decreased life-span in flies upon heart-specific unc-45 knockdown were significantly rescued by UNC-45 over-expression. Our results are the first to demonstrate a cardiac-specific requirement of a chaperone in Drosophila, suggestive of a critical role of UNC-45 in cardiomyopathies, including those associated with unfolded proteins in the failing human heart. The dilated cardiomyopathy phenotype associated with UNC-45 deficiency is mimicked by myosin knockdown suggesting that UNC-45 plays a crucial role in stabilizing myosin and possibly preventing human cardiomyopathies associated with functional deficiencies of myosin. PMID:21799905
The business concept of leader pricing as applied to heart failure disease management.
Hauptman, Paul J; Bednarek, Heather L
2004-01-01
The implementation of a disease management approach for patients with heart failure has been promoted as a way to improve outcomes, including a decrease in hospitalizations. However, in the absence of rigorous cost analyses and with revenues limited by professional fees, heart failure disease management programs may appear to operate at a loss. The literature outlining the importance of disease management for patients with heart failure is summarized. We review the limitations of current cost analyses and outline the economic concepts of leader pricing, vertical integration and transaction costs to argue that heart failure disease management programs may provide significant "downstream" revenue for an integrated system of health care delivery in a fee-for-service payment structure, while reducing overall costs of care. Pilot data from a university-based program are used in support of this argument. In addition, the favorable impact on patient satisfaction and loyalty can enhance market share, a vital consideration for all health systems. Options for improving the reputation of heart failure disease management within a health system are suggested. Viewed as a loss leader, disease management provides not only quality care for patients with heart failure but also appears to provide financial benefits to the health system that funds the infrastructure and administration of the program. The actual magnitude of this benefit and the degree to which it mitigates overall administration costs requires further study.
Probability of detection of clinical seizures using heart rate changes.
Osorio, Ivan; Manly, B F J
2015-08-01
Heart rate-based seizure detection is a viable complement or alternative to ECoG/EEG. This study investigates the role of various biological factors on the probability of clinical seizure detection using heart rate. Regression models were applied to 266 clinical seizures recorded from 72 subjects to investigate if factors such as age, gender, years with epilepsy, etiology, seizure site origin, seizure class, and data collection centers, among others, shape the probability of EKG-based seizure detection. Clinical seizure detection probability based on heart rate changes, is significantly (p<0.001) shaped by patients' age and gender, seizure class, and years with epilepsy. The probability of detecting clinical seizures (>0.8 in the majority of subjects) using heart rate is highest for complex partial seizures, increases with a patient's years with epilepsy, is lower for females than for males and is unrelated to the side of hemisphere origin. Clinical seizure detection probability using heart rate is multi-factorially dependent and sufficiently high (>0.8) in most cases to be clinically useful. Knowledge of the role that these factors play in shaping said probability will enhance its applicability and usefulness. Heart rate is a reliable and practical signal for extra-cerebral detection of clinical seizures originating from or spreading to central autonomic network structures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Analysis of cardiomyocyte movement in the developing murine heart
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hashimoto, Hisayuki; Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp; Tabata, Hidenori
The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cellmore » cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.« less
Yuan, Chen-Ching; Muthu, Priya; Kazmierczak, Katarzyna; ...
2015-06-29
Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 →Valine) mutation-induced changes in heart morphology and function coincided with largely reduced RLC phosphorylation in situ. In this paper, we hypothesized that the introduction of a constitutively phosphorylated Serine15 (S15D) into the hearts of D166V mice would prevent the development of a deleterious HCM phenotype. In supportmore » of this notion, MLCK-induced phosphorylation of D166V-mutated hearts was found to rescue some of their abnormal contractile properties. Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and morphological assessments. The results were compared with Tg-WT and Tg-D166V mice expressing the human ventricular RLC-WT or its D166V mutant, respectively. Echocardiography and invasive hemodynamic studies demonstrated significant improvements of intact heart function in S15D-D166V mice compared with D166V, with the systolic and diastolic indices reaching those monitored in WT mice. A largely reduced maximal tension and abnormally high myofilament Ca 2+ sensitivity observed in D166V-mutated hearts were reversed in S15D-D166V mice. Low-angle X-ray diffraction study revealed that altered myofilament structures present in HCM-D166V mice were mitigated in S15D-D166V rescue mice. Finally, our collective results suggest that expression of pseudophosphorylated RLC in the hearts of HCM mice is sufficient to prevent the development of the pathological HCM phenotype.« less
Xie, Weihong; Yu, Yang
2017-01-01
Robot-assisted motion compensated beating heart surgery has the advantage over the conventional Coronary Artery Bypass Graft (CABG) in terms of reduced trauma to the surrounding structures that leads to shortened recovery time. The severe nonlinear and diverse nature of irregular heart rhythm causes enormous difficulty for the robot to realize the clinic requirements, especially under arrhythmias. In this paper, we propose a fusion prediction framework based on Interactive Multiple Model (IMM) estimator, allowing each model to cover a distinguishing feature of the heart motion in underlying dynamics. We find that, at normal state, the nonlinearity of the heart motion with slow time-variant changing dominates the beating process. When an arrhythmia occurs, the irregularity mode, the fast uncertainties with random patterns become the leading factor of the heart motion. We deal with prediction problem in the case of arrhythmias by estimating the state with two behavior modes which can adaptively “switch” from one to the other. Also, we employed the signal quality index to adaptively determine the switch transition probability in the framework of IMM. We conduct comparative experiments to evaluate the proposed approach with four distinguished datasets. The test results indicate that the new proposed approach reduces prediction errors significantly. PMID:29124062
Liang, Fan; Xie, Weihong; Yu, Yang
2017-01-01
Robot-assisted motion compensated beating heart surgery has the advantage over the conventional Coronary Artery Bypass Graft (CABG) in terms of reduced trauma to the surrounding structures that leads to shortened recovery time. The severe nonlinear and diverse nature of irregular heart rhythm causes enormous difficulty for the robot to realize the clinic requirements, especially under arrhythmias. In this paper, we propose a fusion prediction framework based on Interactive Multiple Model (IMM) estimator, allowing each model to cover a distinguishing feature of the heart motion in underlying dynamics. We find that, at normal state, the nonlinearity of the heart motion with slow time-variant changing dominates the beating process. When an arrhythmia occurs, the irregularity mode, the fast uncertainties with random patterns become the leading factor of the heart motion. We deal with prediction problem in the case of arrhythmias by estimating the state with two behavior modes which can adaptively "switch" from one to the other. Also, we employed the signal quality index to adaptively determine the switch transition probability in the framework of IMM. We conduct comparative experiments to evaluate the proposed approach with four distinguished datasets. The test results indicate that the new proposed approach reduces prediction errors significantly.
Cong, Weitao; Ruan, Dandan; Xuan, Yuanhu; Niu, Chao; Tao, Youli; Wang, Yang; Zhan, Kungao; Cai, Lu; Jin, Litai; Tan, Yi
2015-12-01
Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-κB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including α-oxoglutarate dehydrogenase E1 component (α-KGD) and ATP synthase α and β subunits (ATP-α and ATP-β). To assess the effects of the NF-κB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-κB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-κB-dependent inflammatory responses and associated protein nitration. Copyright © 2015 Elsevier Ltd. All rights reserved.
Li, Qian; Lian, Chun-Wei; Fang, Li-Qun; Liu, Bin; Yang, Bo
2014-09-01
To investigate whether xenon preconditioning (PC) could protect immature myocardium against ischemia-reperfusion (I/R) injury in a dose-dependent manner and clarify the role of xenon PC on oxidative stress. Forty-eight isolated perfused immature rabbit hearts were randomly divided into four groups (n = 12): The sham group had the hearts perfused continuously for 300 min. In I/R group, the hearts were subjected to 60 min perfusion followed by 60 min ischemia and 180 min reperfusion. In 1 minimum alveolar concentration (MAC) and 0.5 MAC xenon PC groups, the hearts were preconditioned with 1 MAC or 0.5 MAC xenon respectively, following 60 min ischemia and 180 min reperfusion. The cardiac function, myocardial infarct size, mitochondrial structure, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in each group were determined after reperfusion. Compared with I/R group, both 1 MAC and 0. 5 MAC xenon preconditioning significantly improved cardiac function (P < 0.01), reduced myocardial infarct size (P < 0.01) and mitochondrial damage, increased SOD activity and decreased MDA level (P < 0.01). There were no differences between 1 MAC group and 0.5 MAC xenon group (P > 0.05). Xenon preconditioning at 0. 5 and 1 MAC produce similar cardioprotective effects against I/R injury in isolated perfused immature heart.
Organ, Chelsea L.; Otsuka, Hiroyuki; Bhushan, Shashi; Wang, Zeneng; Bradley, Jessica; Trivedi, Rishi; Polhemus, David J.; Tang, W. H. Wilson; Wu, Yuping; Hazen, Stanley L.; Lefer, David J.
2015-01-01
Background Trimethylamine N-oxide (TMAO), a gut microbe dependent metabolite of dietary choline and other trimethylamine containing nutrients, is both elevated in the circulation of patients suffering from heart failure (HF) and heralds worse overall prognosis. In animal studies, dietary choline or TMAO significantly accelerate atherosclerotic lesion development in ApoE deficient mice, and reduction in TMAO levels inhibits atherosclerosis development in the LDL receptor knockout mouse. Methods and Results C57BL6/J mice were fed either a control diet, a diet containing choline (1.2%) or a diet containing TMAO (0.12%) starting 3 weeks prior to surgical TAC. Mice were studied for 12 weeks following TAC. Cardiac function and left ventricular structure were monitored at 3-week intervals using echocardiography. Twelve weeks post-TAC myocardial tissues were collected to evaluate cardiac and vascular fibrosis, and blood samples were evaluated for cardiac BNP, choline, and TMAO levels. Pulmonary edema, cardiac enlargement, and left ventricular ejection fraction (LVEF) were significantly (p < 0.05, each) worse in mice fed either TMAO or choline supplemented diets compared to the control diet. In addition, myocardial fibrosis was also significantly greater (p < 0.01, each) in the TMAO and choline groups relative to controls. Conclusions Heart failure severity is significantly enhanced in mice fed diets supplemented in either choline or the gut microbe-dependent metabolite TMAO. The present results suggest that further studies are warranted examining whether gut microbiota and the dietary choline -> TMAO pathway contribute to increased heart failure susceptibility. PMID:26699388
Optogenetic pacing in Drosophila models (Conference Presentation)
NASA Astrophysics Data System (ADS)
Wu, Penghe; Li, Airong; Men, Jing; Tans, Rudolph E.; Zhou, Chao
2017-02-01
The Drosophila melanogaster shares many similarities with vertebrates in heart development. Comparison of heart structural and functional characteristic between male and female Drosophila melanogaster at different developmental stages is helpful to understand heart morphogenesis and function for different genders. And also, it opens up the possibility to uncover the role of sex-related genes in heart development. In this longitudinal study, we cultured and tracked dozens of individually labeled flies throughout their lifecycle. The heart characteristic was measured at different developmental stages during culturing. The gender of each individual fly was determined by adult stage so that the collected data of early stages could be classified to male or female group. We adapted a high-speed optical coherence microscopy (OCM) system with axial and transverse resolution of 2um and 4um, respectively, to perform non-invasive M-mode imaging at a frame rate of 132Hz in Drosophila heart at third instar larva, early pupa and adult stage. Based on those GPU processed M-mode OCM images, we segmented the fly heart region and then quantified the cardiac structural and functional parameters such as heart rate, heart chamber size and so on. Despite large variances of wild type Drosophila in terms of some cardiac characteristic, our results suggest that the heart rate is lower for male flies than for female flies, especially at third instar larva stage. The end diastolic area (EDA) and end systolic area (ESA) of the heart are both slightly larger in female flies than in male flies at larva and adult stage. In summary, we showed gender differences of wild type drosophila in heart functional and structural characteristic.
Dronedarone for the treatment of atrial fibrillation and atrial flutter: approval and efficacy.
Wolbrette, Deborah; Gonzalez, Mario; Samii, Soraya; Banchs, Javier; Penny-Peterson, Erica; Naccarelli, Gerald
2010-08-09
Dronedarone, a new Class III antiarrhythmic agent, has now been approved by the US Food and Drug Administration for use in patients with atrial fibrillation or atrial flutter. Approval came in March 2009 due to the positive results of the ATHENA trial showing significant reductions in all-cause mortality and cardiovascular hospitalization with dronedarone use. A post hoc analysis of the ATHENA data also suggested a decrease in stroke risk with this agent. However, due to safety concerns in the heart failure population in the earlier ANDROMEDA trial, dronedarone is not recommended for patients with an ejection fraction <35% and recent decompensated heart failure. Dronedarone is an amiodarone analog with multichannel blocking electrophysiologic properties similar to those of amiodarone, but several structural differences. Dronedarone's lack of the iodine moiety reduces its potential for thyroid and pulmonary toxicity. Preliminary data from the DIONYSOS trial, and an indirect meta-analysis comparing amiodarone with dronedarone, showed amiodarone to be more effective in maintaining sinus rhythm, while dronedarone was associated with fewer adverse effects resulting in early termination of the drug. Dronedarone is the first antiarrhythmic drug for the treatment of atrial fibrillation and atrial flutter shown to reduce cardiovascular hospitalizations. In patients with structural heart disease who have an ejection fraction >35% and no recent decompensated heart failure, dronedarone should be considered earlier than amiodarone in the treatment algorithm.
Kim, Hyemin; Bae, Seyeon; Kim, Yejin; Cho, Chung-Hyun; Kim, Sung Joon; Kim, Yong-Jin; Lee, Seung-Pyo; Kim, Hang-Rae; Hwang, Young-Il; Kang, Jae Seung; Lee, Wang Jae
2013-12-01
It is thought that vitamin C has protective roles on stress-induced heart damage and the development of cardiovascular diseases, but its precise role and mechanisms are unclear. In the present study, we investigated the specific mechanisms by which vitamin C leads to protecting the heart from stress-induced damage in the Gulo(-/-) mice which cannot synthesize vitamin C like humans. By exposure to stress (1h/day), the heartbeat and cardiac output in vitamin C-insufficient Gulo(-/-) mice were definitely decreased, despite a significant increase of adrenaline (ADR) and noradrenaline (NA) production. A change of cardiac structure caused by the death of cardiomyocytes and an increased expression of matrix metalloprotease (MMP)-2 and -9 were also found. Moreover, lipid peroxidation and the production of tumor necrosis factor-alpha (TNF-α) in the heart were increased. Finally, all vitamin C-insufficient Gulo(-/-) mice were expired within 2 weeks. Interestingly, all of the findings in vitamin C-insufficient Gulo(-/-) mice were completely prevented by the supplementation of a sufficient amount of vitamin C. Taken together, vitamin C insufficiency increases the risk of stress-induced cardiac damage with structural and functional changes arising from the apoptosis of cardiomyocytes. Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved.
Pregler, Janet; Freund, Karen M; Kleinman, Mary; Phipps, Maureen G; Fife, Rose S; Gams, Becky; Núñez, Ana E; Seaver, Margaret R; Lazarus, Cathy J; Raymond, Nancy C; Briller, Joan; Uijtdehaage, Sebastian; Moskovic, Cindy S; Guiton, Gretchen; David, Michele; Gabeau, Geralde V; Geller, Stacie; Meekma, Kelli; Moore, Christopher; Robertson, Candace; Sarto, Gloria
2009-10-01
Heart disease is the leading cause of death for women in the United States. Research has identified that women are less likely than men to receive medical interventions for the prevention and treatment of heart disease. As part of a campaign to educate healthcare professionals, 1245 healthcare professionals in 11 states attended a structured 1-hour continuing medical education (CME) program based on the 2004 AHA Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women and completed a pretest and posttest evaluation. We identified significant knowledge deficits in the pretest: 45% of attendees would initially recommend lifestyle changes alone, rather than statin therapy, for women diagnosed with coronary artery disease (CAD); 38% identified statin therapy as less effective in women compared with men for preventing CAD events; 27% identified Asian American women at low risk (rather than high risk) for type 2 diabetes mellitus (DM); and 21% identified processed meat (rather than baked goods) as the principal dietary source of trans fatty acids. Overall, healthcare professionals answered 5.1 of 8 knowledge questions correctly in the pretest, improving to 6.8 questions in the posttest (p < 0.001). Family physicians, obstetrician/gynecologists, general internists, nurse practitioners/physician assistants, and registered nurses all statistically significantly improved knowledge and self-assessed skills and attitudes as measured by the posttest. Significant knowledge deficits are apparent in a cross-section of healthcare providers attending a CME lecture on women and heart disease. A 1-hour presentation was successful in improving knowledge and self-assessed skills and attitudes among primary care physicians, nurse practitioners, physician assistants, and registered nurses.
Wu, S; He, Z; Guo, J; Li, F; Lin, Q; Guan, X
2014-01-01
To assess the heart and lung dosimetry results associated with accelerated partial breast irradiation intensity-modulated radiotherapy (APBI-IMRT) and whole breast field-in-field intensity-modulated radiotherapy (WBI-FIF-IMRT). A total of 29 patients with early-stage breast cancer after lumpectomy were included in this study. APBI-IMRT and WBI-FIF-IMRT plans were generated for each patient. The dosimetric parameters of ipsilateral lung and heart in both plans were then compared with and without radiobiological correction. With and without radiobiological correction, the volume of ipsilateral lung showed a substantially lower radiation exposure in APBI-IMRT with moderate to high doses (P < 0.05) but non-significant increases in volume of ipsilateral lung in 2.5 Gy than WBI-FIF-IMRT (P > 0.905).There was no significant difference in volume of ipsilateral lung receiving 1, 2.5, and 5 Gy between APBI-IMRT and WBI (P > 0.05) in patients with medial tumor location, although APBI-IMRT exposed more lung to 2.5 and 5 Gy. APBI-IMRT significantly decreases the volume of heart receiving low to high doses in left-sided breast cancer (P < 0.05). APBI-IMRT can significantly spare the volume of heart and ipsilateral lung receiving moderate and high dose. Non-significant increases in volume of the ipsilateral lung exposed to low doses of radiation were observed for APBI-IMRT in comparison to WBI-FIF-IMRT, particularly in patients with medial tumor location. With the increasing interest in APBI-IMRT, our data may help clinicians individualize patient treatment decisions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thal, David M.; Homan, Kristoff T.; Chen, Jun
2012-08-10
G protein-coupled receptor kinase 2 (GRK2) is a well-established therapeutic target for the treatment of heart failure. In this paper we identify the selective serotonin reuptake inhibitor (SSRI) paroxetine as a selective inhibitor of GRK2 activity both in vitro and in living cells. In the crystal structure of the GRK2·paroxetine–Gβγ complex, paroxetine binds in the active site of GRK2 and stabilizes the kinase domain in a novel conformation in which a unique regulatory loop forms part of the ligand binding site. Isolated cardiomyocytes show increased isoproterenol-induced shortening and contraction amplitude in the presence of paroxetine, and pretreatment of mice withmore » paroxetine before isoproterenol significantly increases left ventricular inotropic reserve in vivo with no significant effect on heart rate. Neither is observed in the presence of the SSRI fluoxetine. Our structural and functional results validate a widely available drug as a selective chemical probe for GRK2 and represent a starting point for the rational design of more potent and specific GRK2 inhibitors.« less
Imaging techniques for visualizing and phenotyping congenital heart defects in murine models.
Liu, Xiaoqin; Tobita, Kimimasa; Francis, Richard J B; Lo, Cecilia W
2013-06-01
Mouse model is ideal for investigating the genetic and developmental etiology of congenital heart disease. However, cardiovascular phenotyping for the precise diagnosis of structural heart defects in mice remain challenging. With rapid advances in imaging techniques, there are now high throughput phenotyping tools available for the diagnosis of structural heart defects. In this review, we discuss the efficacy of four different imaging modalities for congenital heart disease diagnosis in fetal/neonatal mice, including noninvasive fetal echocardiography, micro-computed tomography (micro-CT), micro-magnetic resonance imaging (micro-MRI), and episcopic fluorescence image capture (EFIC) histopathology. The experience we have gained in the use of these imaging modalities in a large-scale mouse mutagenesis screen have validated their efficacy for congenital heart defect diagnosis in the tiny hearts of fetal and newborn mice. These cutting edge phenotyping tools will be invaluable for furthering our understanding of the developmental etiology of congenital heart disease. Copyright © 2013 Wiley Periodicals, Inc.
Microgravity changes in heart structure and cyclic-AMP metabolism
NASA Technical Reports Server (NTRS)
Philpott, D. E.; Fine, A.; Kato, K.; Egnor, R.; Cheng, L.
1985-01-01
The effects of microgravity on cardiac ultrastructure and cyclic AMP metabolism in tissues of rats flown on Spacelab 3 are reported. Light and electron microscope studies of cell structure, measurements of low and high Km phosphodiesterase activity, cyclic AMP-dependent protein kinase activity, and regulatory subunit compartmentation show significant deviations in flight animals when compared to ground controls. The results indicate that some changes have occurred in cellular responses associated with catecholamine receptor interactions and intracellular signal processing.
Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank
2018-02-01
Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.
Jun, Jin; Faulkner, Kenneth M
2018-04-01
To review the current literature on hospital nursing factors associated with 30-day readmission rates of patients with heart failure. Heart failure is a common, yet debilitating chronic illness with high mortality and morbidity. One in five patients with heart failure will experience unplanned readmission to a hospital within 30 days. Given the significance of heart failure to individuals, families and healthcare system, the Center for Medicare and Medicaid Services has made reducing 30-day readmission rates a priority. Scoping review, which maps the key concepts of a research area, is used. Published primary studies in English assessing factors related to nurses in hospitals and readmission of patients with heart failure were included. Other inclusion criteria were written in English and published in peer-reviewed journals. The search resulted in 2,782 articles. After removing duplicates and reviewing the inclusion and exclusion criteria, five articles were selected. Three nursing workforce factors emerged as follows: (i) nursing staffing, (ii) nursing care and work environment, and (iii) nurses' knowledge of heart failure. This is the first scoping review examining the association between hospital nursing factors and 30-day readmission rates of patients with heart failure. Further studies examining the extent of nursing structural and process factors influencing the outcomes of patients with heart failure are needed. Nurses are an integral part of the healthcare system. Identifying the factors related to nurses in hospitals is important to ensure comprehensive delivery of care to the chronically ill population. Hospital administrators, managers and policymakers can use the findings from this review to implement strategies to reduce 30-day readmission rates of patients with heart failure. © 2018 John Wiley & Sons Ltd.
Hopfield neural network and optical fiber sensor as intelligent heart rate monitor
NASA Astrophysics Data System (ADS)
Mutter, Kussay Nugamesh
2018-01-01
This paper presents a design and fabrication of an intelligent fiber-optic sensor used for examining and monitoring heart rate activity. It is found in the literature that the use of fiber sensors as heart rate sensor is widely studied. However, the use of smart sensors based on Hopfield neural networks is very low. In this work, the sensor is a three fibers without cladding of about 1 cm, fed by laser light of 1550 nm of wavelength. The sensing portions are mounted with a micro sensitive diaphragm to transfer the pulse pressure on the left radial wrist. The influenced light intensity will be detected by a three photodetectors as inputs into the Hopfield neural network algorithm. The latter is a singlelayer auto-associative memory structure with a same input and output layers. The prior training weights are stored in the net memory for the standard recorded normal heart rate signals. The sensors' heads work on the reflection intensity basis. The novelty here is that the sensor uses a pulse pressure and Hopfield neural network in an integrity approach. The results showed a significant output measurements of heart rate and counting with a plausible error rate.
BAG3: a new player in the heart failure paradigm.
Knezevic, Tijana; Myers, Valerie D; Gordon, Jennifer; Tilley, Douglas G; Sharp, Thomas E; Wang, JuFang; Khalili, Kamel; Cheung, Joseph Y; Feldman, Arthur M
2015-07-01
BAG3 is a cellular protein that is expressed predominantly in skeletal and cardiac muscle but can also be found in the brain and in the peripheral nervous system. BAG3 functions in the cell include: serving as a co-chaperone with members of the heat-shock protein family of proteins to facilitate the removal of misfolded and degraded proteins, inhibiting apoptosis by interacting with Bcl2 and maintaining the structural integrity of the Z-disk in muscle by binding with CapZ. The importance of BAG3 in the homeostasis of myocytes and its role in the development of heart failure was evidenced by the finding that single allelic mutations in BAG3 were associated with familial dilated cardiomyopathy. Furthermore, significant decreases in the level of BAG3 have been found in end-stage failing human heart and in animal models of heart failure including mice with heart failure secondary to trans-aortic banding and in pigs after myocardial infarction. Thus, it becomes relevant to understand the cellular biology and molecular regulation of BAG3 expression in order to design new therapies for the treatment of patients with both hereditary and non-hereditary forms of dilated cardiomyopathy.
Tricuspid Regurgitation – Medical Management and Evolving Interventional Concepts
Beckhoff, Frederik; Alushi, Brunilda; Jung, Christian; Navarese, Eliano; Franz, Marcus; Kretzschmar, Daniel; Wernly, Bernhard; Lichtenauer, Michael; Lauten, Alexander
2018-01-01
Severe tricuspid regurgitation (TR) is a complex condition of the right ventricle (RV) and tricuspid valve apparatus and is frequently associated with symptomatic heart failure and a significant morbidity and mortality. In these patients, left heart pathologies lead to chronic pressure overload of the RV, eventually causing progressive RV dilatation and functional TR. Therefore, TR cannot be considered as isolated heart valve disease pathology but has to be understood and treated as one component of a complex structural RV pathology and is frequently also a marker of an advanced stage of cardiac disease. In these patients, medical therapy restricted to diuretics and heart failure medication is frequently ineffective. Also, severe TR in the setting of advanced heart failure constitutes a high risk for cardiac surgery. Neither one of these treatment options has demonstrated a beneficial effect on long-term prognosis. The recent innovations in transcatheter technology led to efforts to develop interventional approaches to severe TR. Multiple innovative treatment concepts are currently under preclinical and clinical investigation to replace or repair TV function. However, up to date none of these approaches is established and there is still a lack of clinical data to support the efficacy of transcatheter TR treatment. PMID:29892601
Chaos in the heart: the interaction between body and mind
NASA Astrophysics Data System (ADS)
Redington, Dana
1993-11-01
A number of factors influence the chaotic dynamics of heart function. Genetics, age, sex, disease, the environment, experience, and of course the mind, play roles in influencing cardiovascular dynamics. The mind is of particular interest because it is an emergent phenomenon of the body admittedly seated and co-occurrent in the brain. The brain serves as the body's controller, and commands the heart through complex multipathway feedback loops. Structures deep within the brain, the hypothalamus and other centers in the brainstem, modulate heart function, partially as a result of afferent input from the body but also a result of higher mental processes. What can chaos in the body, i.e., the nonlinear dynamics of the heart, tell of the mind? This paper presents a brief overview of the spectral structure of heart rate activity followed by a summary of experimental results based on phase space analysis of data from semi-structured interviews. This paper then describes preliminary quantification of cardiovascular dynamics during different stressor conditions in an effort to apply more quantitative methods to clinical data.
Atrial fibrillation driver mechanisms: Insight from the isolated human heart.
Csepe, Thomas A; Hansen, Brian J; Fedorov, Vadim V
2017-01-01
Although there have been great technological advances in the treatment of atrial fibrillation (AF), current therapies remain limited due to a narrow understanding of AF mechanisms in the human heart. This review will highlight our recent studies on explanted human hearts where we developed and employed a novel functional-structural mapping approach by integrating high-resolution simultaneous endo-epicardial and panoramic optical mapping with 3D gadolinium-enhanced MRI to define the spatiotemporal characteristics of AF drivers and their structural substrates. The results allow us to postulate that the primary mechanism of AF maintenance in human hearts is a limited number of localized intramural microanatomic reentrant AF drivers anchored to heart-specific 3D fibrotically insulated myobundle tracks, which may remain hidden to clinical single-surface electrode mapping. We suggest that ex vivo human heart studies, by using an integrated 3D functional and structural mapping approach, will help to reveal defining features of AF drivers as well as validate and improve clinical approaches to detect and target these AF drivers in patients with cardiac diseases. Copyright © 2016 Elsevier Inc. All rights reserved.
Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management.
Meagher, Patrick; Adam, Mohamed; Civitarese, Robert; Bugyei-Twum, Antoinette; Connelly, Kim A
2018-05-01
Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as "diabetic cardiomyopathy." Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition. There is a myriad of mechanisms that result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate utilization, altered insulin signalling leading to protein kinase C activation, advanced glycated end products deposition, prosclerotic cytokine activation (eg, transforming growth factor-β activation), along with impaired nitric oxide production from the endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte interactions. Despite intense research, current therapeutic strategies have had little effect on improving morbidity and mortality in patients with DM and HFpEF. Possible explanations for this include a limited understanding of the role that direct cell-cell communication or indirect cell-cell paracrine signalling plays in the pathogenesis of DM and HFpEF. Additionally, integrins remain another important mediator of signals from the extracellular matrix to cells within the failing heart and might play a significant role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms of DM and HFpEF to stimulate potential future research for patients with this common, and morbid condition. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Mulligan, Christopher M.; Sparagna, Genevieve C.; Le, Catherine H.; De Mooy, Anthony B.; Routh, Melissa A.; Holmes, Michael G.; Hickson-Bick, Diane L.; Zarini, Simona; Murphy, Robert C.; Xu, Fred Y.; Hatch, Grant M.; McCune, Sylvia A.; Moore, Russell L.; Chicco, Adam J.
2012-01-01
Aims Cardiolipin (CL) is a tetra-acyl phospholipid that provides structural and functional support to several proteins in the inner mitochondrial membrane. The majority of CL in the healthy mammalian heart contains four linoleic acid acyl chains (L4CL). A selective loss of L4CL is associated with mitochondrial dysfunction and heart failure in humans and animal models. We examined whether supplementing the diet with linoleic acid would preserve cardiac L4CL and attenuate mitochondrial dysfunction and contractile failure in rats with hypertensive heart failure. Methods and results Male spontaneously hypertensive heart failure rats (21 months of age) were administered diets supplemented with high-linoleate safflower oil (HLSO) or lard (10% w/w; 28% kilocalorie fat) or without supplemental fat (control) for 4 weeks. HLSO preserved L4CL and total CL to 90% of non-failing levels (vs. 61–75% in control and lard groups), and attenuated 17–22% decreases in state 3 mitochondrial respiration observed in the control and lard groups (P < 0.05). Left ventricular fractional shortening was significantly higher in HLSO vs. control (33 ± 2 vs. 29 ± 2%, P < 0.05), while plasma insulin levels were lower (5.4 ± 1.1 vs. 9.1 ± 2.3 ng/mL; P < 0.05), with no significant effect of lard supplementation. HLSO also increased serum concentrations of several eicosanoid species compared with control and lard diets, but had no effect on plasma glucose or blood pressure. Conclusion Moderate consumption of HLSO preserves CL and mitochondrial function in the failing heart and may be a useful adjuvant therapy for this condition. PMID:22411972
Left Ventricular Aneurysm: Sudden Unexpected Deaths in a 29-Year-Old Man.
Srettabunjong, Supawon
2018-05-01
Left ventricular aneurysm (LVA) is an abnormal dilated heart structure, either congenital or acquired. LVA is a rare cardiac condition with no symptoms in most cases, thus occasionally diagnosed during investigations of other diseases. Its association with certain cardiac complications and sudden cardiac deaths has been reported. However, its role as a cause of sudden unexpected death is rare. The author reported a sudden cardiac death in a 29-year-old man with LVA. Without a significant coronary artery disease and known etiologies of LVA, such an abnormal heart structure in the present case was considered congenital LVA. As no other possible mechanisms of death could be identified other than LVA with its associated pathologic lesions, mural thrombi, and dilated cardiomegaly, his death was attributable to fatal cardiac arrhythmia (most commonly ventricular tachycardia) secondary to LVA. © 2017 American Academy of Forensic Sciences.
There Is More to the Dissection of a Pig's Heart
ERIC Educational Resources Information Center
Lee, Yeung Chung
2004-01-01
The dissection of the mammalian heart in secondary biology classes need not be restricted to revealing the internal structure of the heart and its function. It could also be used to demonstrate other important aspects of blood circulation, including the blood supply to the heart itself as well as the causes and effects of coronary heart disease.…
Small molecule inhibitors of human adipocyte fatty acid binding protein (FABP4).
Zhang, Mingming; Zhu, Weiliang; Li, Yingxia
2014-06-01
Fatty acid binding protein 4 (FABP4) is expressed in adipocytes and macrophages, and modulates inflammatory and metabolic response. Studies in FABP4-deficient mice have shown that this lipid carrier has a significant role within the field of metabolic syndrome, inflammation and atherosclerosis; thus, its inhibition may open up new opportunities to develop novel therapeutic agents. A number of potent small molecule inhibitors of FABP4 have been identified and found to have the potential to prevent and treat metabolic diseases such as type-2 diabetes and atherosclerosis. Due to the ubiquity of endogenous fatty acids and the high intracellular concentration of FABP4, the inhibitors need to have significantly greater intrinsic potency than endogenous fatty acids. Furthermore, heart-type FABP (FABP3), which is expressed in both heart and skeletal muscle, is involved in active fatty acid metabolism where it transports fatty acids from the cell membrane to mitochondria for oxidation. However, FABP3 shares high overall sequence identity and similar 3D structure with FABP4, but has a potential problem with selectivity. In this review, we would like to analyze the main inhibitors that have appeared in the literature in the last decade, focusing on chemical structures, biological properties, selectivity and structure-activity relationships.
Potential implications of the helical heart in congenital heart defects.
Corno, Antonio F; Kocica, Mladen J
2007-01-01
The anatomic and functional observations made by Francisco Torrent-Guasp, in particular his discovery of the helical ventricular myocardial band (HVMB), have challenged what has been taught to cardiologists and cardiac surgeons over centuries. A literature debate is ongoing, with interdependent articles and comments from supporters and critics. Adequate understanding of heart structure and function is obviously indispensable for the decision-making process in congenital heart defects. The HVMB described by Torrent-Guasp and the potential impact on the understanding and treatment of congenital heart defects has been analyzed in the following settings: embryology, ventriculo-arterial discordance (transposition of great arteries), Ebstein's anomaly, pulmonary valve regurgitation after repair of tetralogy of Fallot, Ross operation, and other congenital heart defects. The common structural spiral feature is only one of the elements responsible for the functional interaction of right and left ventricles, and understanding the form/function relationship in congenital heart defects is more difficult than for acquired heart disease because of the variety and complexity of congenital heart defects. Individuals involved in the care of patients with congenital heart defects have to be stimulated to consider further investigations and alternative surgical strategies.
Sohail, Aamir; Faraz, Mohd; Arif, Hussain; Bhat, Sheraz Ahmad; Siddiqui, Azad Alam; Bano, Bilqees
2017-02-01
ZnO-NPs have been widely used in biomedical fields such as therapeutics, cellular imaging, and drug delivery. However, the risk of exposure of nanoparticles to the biological system is not well understood. Nanoparticle-protein interaction is pivotal to understand their biological behavior and predict nanoparticle toxicity that is crucial for its safer applications. In the present study zinc oxide nanoparticles (ZnO-NPs) were synthesized and subjected to interact with buffalo heart cystatin (BHC), purified from buffalo heart, to assess the effect(s) of ZnO-NPs on the structure and function of BHC. In vitro toxicity assessments revealed that BHC, upon interaction with ZnO-NPs, led to the altered protein conformation and perturbed function. A decrease in the anti-papain activity of BHC was observed. Spectroscopic studies demonstrated that formation of BHC-ZnO-NPs complex accompanied by structural changes in BHC along with a significant decrease in its α-helical content. ITC determined the thermodynamic parameters of binding between ZnO-NPs and BHC quantitatively. Increased surface hydrophobicity (change in the tertiary structure) was observed by ANS fluorescence that demonstrated the formation of molten globular intermediates that were found to be stable without any signs of aggregation as depicted by ThT fluorescence. TEM images gave the physical evidence of the formation of ZnO-NPs-BHC corona. Copyright © 2016. Published by Elsevier B.V.
Studying the Microanatomy of the Heart in Three Dimensions: A Practical Update
Jarvis, Jonathan C.; Stephenson, Robert
2013-01-01
The structure and function of the heart needs to be understood in three dimensions. We give a brief historical summary of the methods by which such an understanding has been sought, and some practical details of the relatively new technique of micro-CT with iodine contrast enhancement in samples from rat and rabbit. We discuss how the improved anatomical detail available in fixed cadaveric hearts will enhance our ability to model and to understand the integrated function of the cardiomyocytes, conducting tissues, and fibrous supporting structures that generate the pumping function of the heart. PMID:24400272
Yasuno, Shinji; Kuwahara, Koichiro; Kinoshita, Hideyuki; Yamada, Chinatsu; Nakagawa, Yasuaki; Usami, Satoru; Kuwabara, Yoshihiro; Ueshima, Kenji; Harada, Masaki; Nishikimi, Toshio; Nakao, Kazuwa
2013-12-01
Angiotensin II has been implicated in the development of various cardiovascular ailments, including cardiac hypertrophy and heart failure. The fact that inhibiting its signalling reduced the incidences of both sudden cardiac death and heart failure in several large-scale clinical trials suggests that angiotensin II is involved in increased cardiac arrhythmogenicity during the development of heart failure. However, because angiotensin II also promotes structural remodelling, including cardiomyocyte hypertrophy and cardiac fibrosis, it has been difficult to assess its direct contribution to cardiac arrhythmogenicity independently of the structural effects. We induced cardiac hypertrophy in wild-type (WT) and angiotensin II type 1a receptor knockout (AT1aR-KO) mice by transverse aortic constriction (TAC). The susceptibility to ventricular tachycardia (VT) assessed in an in vivo electrophysiological study was compared in the two genotypes. The effect of acute pharmacological blockade of AT1R on the incidences of arrhythmias was also assessed. As described previously, WT and AT1aR-KO mice with TAC developed cardiac hypertrophy to the same degree, but the incidence of VT was much lower in the latter. Moreover, although TAC induced an increase in tyrosine phosphorylation of connexin 43, a critical component of gap junctional channels, and a reduction in ventricular levels of connexin 43 protein in both genotypes, the effect was significantly ameliorated in AT1aR-KO mice. Acute pharmacological blockade of AT1R also reduced the incidence of arrhythmias. Our findings demonstrate that AT1aR-mediated signalling makes a direct contribution to the increase in arrhythmogenicity in hypertrophied hearts independently of structural remodelling. © 2013 The British Pharmacological Society.
Wall, Christopher E; Cozza, Steven; Riquelme, Cecilia A; McCombie, W Richard; Heimiller, Joseph K; Marr, Thomas G; Leinwand, Leslie A
2011-01-01
The infrequently feeding Burmese python (Python molurus) experiences significant and rapid postprandial cardiac hypertrophy followed by regression as digestion is completed. To begin to explore the molecular mechanisms of this response, we have sequenced and assembled the fasted and postfed Burmese python heart transcriptomes with Illumina technology using the chicken (Gallus gallus) genome as a reference. In addition, we have used RNA-seq analysis to identify differences in the expression of biological processes and signaling pathways between fasted, 1 day postfed (DPF), and 3 DPF hearts. Out of a combined transcriptome of ∼2,800 mRNAs, 464 genes were differentially expressed. Genes showing differential expression at 1 DPF compared with fasted were enriched for biological processes involved in metabolism and energetics, while genes showing differential expression at 3 DPF compared with fasted were enriched for processes involved in biogenesis, structural remodeling, and organization. Moreover, we present evidence for the activation of physiological and not pathological signaling pathways in this rapid, novel model of cardiac growth in pythons. Together, our data provide the first comprehensive gene expression profile for a reptile heart.
Nutrition and growth in congenital heart disease: a challenge in children.
Medoff-Cooper, Barbara; Ravishankar, Chitra
2013-03-01
Growth failure secondary to feeding problems after complex neonatal cardiac surgery is well documented, but not well understood. The purpose of this review is to describe feeding and growth pattern in children with congenital heart defects. Nearly half of the infants with univentricular heart defects require supplementation with nasogastric or gastrostomy tube at discharge from neonatal surgery. Feeding challenges contribute to parental stress, and persist beyond infancy. These infants are 'stunted' with both weight and height being below normal. Nearly a quarter of these infants meet the definition of 'failure to thrive' in the first year of life. Short stature is a significant problem for many of these children, and has an impact on neurodevelopmental outcomes. A structured nutritional program can have a positive impact on growth in the interstage period prior to the superior cavopulmonary connection. Optimizing nutritional intake has been targeted as a key component of the National Pediatric Cardiology Quality Improvement Collaborative. This initiative has enabled the development of best practices that have the potential to mitigate poor growth in children with congenital heart defects.
Self-care and depression in patients with chronic heart failure.
Holzapfel, Nicole; Löwe, Bernd; Wild, Beate; Schellberg, Dieter; Zugck, Christian; Remppis, Andrew; Katus, Hugo A; Haass, Markus; Rauch, Bernhard; Jünger, Jana; Herzog, Wolfgang; Müller-Tasch, Thomas
2009-01-01
Although chronic heart failure (CHF) is often complicated by comorbid depression and poor self-care, little is known about their specific association in patients with CHF. To investigate self-care behavior among patients with CHF with different degrees of depression severity. A total of 287 patients with documented CHF, New York Heart Association functional class II to IV, completed the European Heart Failure Self-Care Behavior Scale. The Structured Clinical Interview for DSM (SCID) IV served as the criterion standard for the presence of a depressive disorder. Analyses of covariance and linear regression analyses revealed that patients with CHF with minor depression reported significantly lower levels of self-care than patients with major depression (P = .003) and nondepressed patients (P = .014). In addition to minor depression, age (P < or = .001), multimorbidity (P = .01), left ventricular ejection fraction (P = .001), and family status (P = .01) were determinants of self-care. Our results demonstrate that patients with CHF with minor depression and not major depression are at higher risk for poor self-care and its resulting consequences, such as symptom deterioration and frequent hospitalization.
Scientific psychology within the Chinese language and cultural context.
Shen, Heyong
2006-01-01
The Scientific Psychology that was founded by Wilhelm Wundt appeared in China in the late nineteenth century. The scholars translated the name of psychology into Chinese as Xin-Li-Xue, for which the meaning of the words looks like "heartology," i.e., "the study of the heart." In Chinese, the same core structure related to "heart" (Xin) is found in most of the terms of psychology, such as emotion, thinking, will, forgetting, and memory. By translating Xin as "heart" instead of "mind," we maintain an embodied approach to understanding the "principles of the heart." Through a historical approach to the influence of Western psychology, a cultural analysis of the meaning of the term psychology in Chinese, and a focus on the meeting of Eastern and Western psychology, we can witness the significance of psychology in the Chinese language and cultural context. I will use three parts to present psychology in the Chinese cultural context: the origins of Chinese psychology, from a historical approach; the meaning of "psychology" in Chinese, using a cultural analysis; and the meeting of Eastern and Western psychology, focusing on the development and future.
Kang, Xiaofeng; Dennison Himmelfarb, Cheryl R; Li, Zheng; Zhang, Jian; Lv, Rong; Guo, Jinyu
2015-01-01
The Self-care of Heart Failure Index (SCHFI) is an empirically tested instrument for measuring the self-care of patients with heart failure. The aim of this study was to develop a simplified Chinese version of the SCHFI and provide evidence for its construct validity. A total of 182 Chinese with heart failure were surveyed. A 2-step structural equation modeling procedure was applied to test construct validity. Factor analysis showed 3 factors explaining 43% of the variance. Structural equation model confirmed that self-care maintenance, self-care management, and self-care confidence are indeed indicators of self-care, and self-care confidence was a positive and equally strong predictor of self-care maintenance and self-care management. Moreover, self-care scores were correlated with the Partners in Health Scale, indicating satisfactory concurrent validity. The Chinese version of the SCHFI is a theory-based instrument for assessing self-care of Chinese patients with heart failure.
Paradis, Alexandra N.; Gay, Maresha S.; Wilson, Christopher G.; Zhang, Lubo
2015-01-01
In the developing heart, cardiomyocytes undergo terminal differentiation during a critical window around birth. Hypoxia is a major stress to preterm infants, yet its effect on the development and maturation of the heart remains unknown. We tested the hypothesis in a rat model that newborn anoxia accelerates cardiomyocyte terminal differentiation and results in reduced cardiomyocyte endowment in the developing heart via an endothelin-1-dependent mechanism. Newborn rats were exposed to anoxia twice daily from postnatal day 1 to 3, and hearts were isolated and studied at postnatal day 4 (P4), 7 (P7), and 14 (P14). Anoxia significantly increased HIF-1α protein expression and pre-proET-1 mRNA abundance in P4 neonatal hearts. Cardiomyocyte proliferation was significantly decreased by anoxia in P4 and P7, resulting in a significant reduction of cardiomyocyte number per heart weight in the P14 neonates. Furthermore, the expression of cyclin D2 was significantly decreased due to anoxia, while p27 expression was increased. Anoxia has no significant effect on cardiomyocyte binucleation or myocyte size. Consistently, prenatal hypoxia significantly decreased cardiomyocyte proliferation but had no effect on binucleation in the fetal heart. Newborn administration of PD156707, an ETA-receptor antagonist, significantly increased cardiomyocyte proliferation at P4 and cell size at P7, resulting in an increase in the heart to body weight ratio in P7 neonates. In addition, PD156707 abrogated the anoxia-mediated effects. The results suggest that hypoxia and anoxia via activation of endothelin-1 at the critical window of heart development inhibits cardiomyocyte proliferation and decreases myocyte endowment in the developing heart, which may negatively impact cardiac function later in life. PMID:25692855
Zhao, Jing; He, Fei; Hu, Da-yi; Ding, Rong-jing; Yu, Xiao-jun; Wang, Long; Zhang, Ping; Li, Xue-bin; Guo, Ji-hong; Liu, Wen-ling; Li, Cui-lan; Li, Lei; Gao, Chuan-yu; Zhao, Luo-sha; Chu, Ying-jie; Huang, Zhen-wen; Wei, Jing-han; Hua, Shao-hua; Liu, Rui-yun; Zhuang, Xiao-feng
2013-05-01
To investigate the basic characteristics of passive smoking population, and the impact of passive smoking on heart rate variability, heart rate and blood pressure. Eighty-six passive smokers [mean age: (52.4 ± 7.6) years] were recruited from patients and their relatives who visited cardiovascular outpatient department and excluded structural heart disease between June 2010 and June 2012, 80 normal subjects who were not exposed to smoking served as controls. Questionnaire survey, 24 hours ambulatory electrocardiogram examination and blood pressure measurement were performed in all recruited subjects. (1) Non-marriage rate [18.60% (16/86) vs. 3.75% (3/80), P < 0.01] was significantly higher while education level were significantly lower in passive smoking group than in control group. Passive smokers were more likely service industry workers [29.07% (25/86) vs. 15.00% (12/80), P < 0.05] and had longer daily working time [(7.56 ± 1.24) h vs. (6.02 ± 0.96) h, P < 0.01], and were less likely to be professional technology industry employers [20.93% (18/86) vs. 36.25% (29/80), P < 0.05] and managers [13.95% (12/86) vs. 38.75% (31/80), P < 0.01] compared to controls. The main place of passive smoking was workplace (67.44%, 58/86), entertainment venues (63.95%,55/86), restaurants (48.84%, 42/86). (2) Standard of the normal sinus RR intervals (SDNN), the normal consecutive sinus RR interval difference between the root-mean-square (rMSSD) and adjacent the difference between the RR interval>50 ms the number of share the percentage (PNN50) were significantly lower in passive smoking group than in the control group (all P < 0.05). Every 5 min average of the standard deviation of sinus RR cycle (SDNN index) and 24 h every 5 min sinus RR interval mean standard deviation (SDANN) were similar between the 2 groups (all P > 0.05). Ultra-low-frequency power (VLF), low frequency power (LF), high frequency power (HF) and LF/HF were significantly lower in passive smoking group than in the control group (all P < 0.01). (3) Heart rate and diastolic blood pressure were significantly higher in passive smoking group than in control group (all P < 0.05) while systolic blood pressure was similar between the 2 groups (P > 0.05). Marriage status, education level, profession and daily working time are independent determinants for passive smoking. Passive smoking mainly occurred in the workplace, entertainment venues and restaurants. Passive smoking is linked with reduced heart rate variability, increased 24 h average heart rate and diastolic blood pressure.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yan, Lifeng; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029; Zhou, Yong
Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes andmore » nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.« less
Prostaglandins are important in thermoregulation of a reptile (Pogona vitticeps).
Seebacher, Frank; Franklin, Craig E
2003-01-01
The effectiveness of behavioural thermoregulation in reptiles is amplified by cardiovascular responses, particularly by differential rates of heart beat in response to heating and cooling (heart-rate hysteresis). Heart-rate hysteresis is ecologically important in most lineages of ectothermic reptile, and we demonstrate that heart-rate hysteresis in the lizard Pogona vitticeps is mediated by prostaglandins. In a control treatment (administration of saline), heart rates during heating were significantly faster than during cooling at any given body temperature. When cyclooxygenase 1 and 2 enzymes were inhibited, heart rates during heating were not significantly different from those during cooling. Administration of agonists showed that thromboxane B(2) did not have a significant effect on heart rate, but prostacyclin and prostaglandin F(2alpha) caused a significant increase (3.5 and 13.6 beats min(-1), respectively) in heart rate compared with control treatments. We speculate that heart-rate hysteresis evolved as a thermoregulatory mechanism that may ultimately be controlled by neurally induced stimulation of nitric oxide production, or maybe via photolytically induced production of vitamin D. PMID:12952634
Prostaglandins are important in thermoregulation of a reptile (Pogona vitticeps).
Seebacher, Frank; Franklin, Craig E
2003-08-07
The effectiveness of behavioural thermoregulation in reptiles is amplified by cardiovascular responses, particularly by differential rates of heart beat in response to heating and cooling (heart-rate hysteresis). Heart-rate hysteresis is ecologically important in most lineages of ectothermic reptile, and we demonstrate that heart-rate hysteresis in the lizard Pogona vitticeps is mediated by prostaglandins. In a control treatment (administration of saline), heart rates during heating were significantly faster than during cooling at any given body temperature. When cyclooxygenase 1 and 2 enzymes were inhibited, heart rates during heating were not significantly different from those during cooling. Administration of agonists showed that thromboxane B(2) did not have a significant effect on heart rate, but prostacyclin and prostaglandin F(2alpha) caused a significant increase (3.5 and 13.6 beats min(-1), respectively) in heart rate compared with control treatments. We speculate that heart-rate hysteresis evolved as a thermoregulatory mechanism that may ultimately be controlled by neurally induced stimulation of nitric oxide production, or maybe via photolytically induced production of vitamin D.
4D blood flow mapping using SPIM-microPIV in the developing zebrafish heart
NASA Astrophysics Data System (ADS)
Zickus, Vytautas; Taylor, Jonathan M.
2018-02-01
Fluid-structure interaction in the developing heart is an active area of research in developmental biology. However, investigation of heart dynamics is mostly limited to computational uid dynamics simulations using heart wall structure information only, or single plane blood ow information - so there is a need for 3D + time resolved data to fully understand cardiac function. We present an imaging platform combining selective plane illumination microscopy (SPIM) with micro particle image velocimetry (μPIV) to enable 3D-resolved flow mapping in a microscopic environment, free from many of the sources of error and bias present in traditional epi uorescence-based μPIV systems. By using our new system in conjunction with optical heart beat synchronization, we demonstrate the ability obtain non-invasive 3D + time resolved blood flow measurements in the heart of a living zebrafish embryo.
Wang, Shan-Shan; Zhang, Yu-Qi; Chen, Shu-Bao; Huang, Guo-Ying; Zhang, Hong-Yan; Zhang, Zhi-Fang; Wu, Lan-Ping; Hong, Wen-Jing; Shen, Rong; Liu, Yi-Qing; Zhu, Jun-Xue
2017-06-01
Clinical decision making in children with congenital and acquired heart disease relies on measurements of cardiac structures using two-dimensional echocardiography. We aimed to establish z-score regression equations for right heart structures in healthy Chinese Han children. Two-dimensional and M-mode echocardiography was performed in 515 patients. We measured the dimensions of the pulmonary valve annulus (PVA), main pulmonary artery (MPA), left pulmonary artery (LPA), right pulmonary artery (RPA), right ventricular outflow tract at end-diastole (RVOTd) and at end-systole (RVOTs), tricuspid valve annulus (TVA), right ventricular inflow tract at end-diastole (RVIDd) and at end-systole (RVIDs), and right atrium (RA). Regression analyses were conducted to relate the measurements of right heart structures to 4body surface area (BSA). Right ventricular outflow-tract fractional shortening (RVOTFS) was also calculated. Several models were used, and the best model was chosen to establish a z-score calculator. PVA, MPA, LPA, RPA, RVOTd, RVOTs, TVA, RVIDd, RVIDs, and RA (R 2 = 0.786, 0.705, 0.728, 0.701, 0.706, 0.824, 0.804, 0.663, 0.626, and 0.793, respectively) had a cubic polynomial relationship with BSA; specifically, measurement (M) = β0 + β1 × BSA + β2 × BSA 2 + β3 × BSA. 3 RVOTFS (0.28 ± 0.02) fell within a narrow range (0.12-0.51). Our results provide reference values for z scores and regression equations for right heart structures in Han Chinese children. These data may help interpreting the routine clinical measurement of right heart structures in children with congenital or acquired heart disease. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:293-303, 2017. © 2017 Wiley Periodicals, Inc.
Skali, Hicham; Shah, Amil; Gupta, Deepak K; Cheng, Susan; Claggett, Brian; Liu, Jiankang; Bello, Natalie; Aguilar, David; Vardeny, Orly; Matsushita, Kunihiro; Selvin, Elizabeth; Solomon, Scott
2015-05-01
Individuals with diabetes mellitus and pre-diabetes mellitus are at particularly high risk of incident heart failure or death, even after accounting for known confounders. Nevertheless, the extent of impairments in cardiac structure and function in elderly individuals with diabetes mellitus and pre-diabetes mellitus is not well known. We aimed to assess the relationship between echocardiographic measures of cardiac structure and function and dysglycemia. We assessed measures of cardiac structure and function in 4419 participants without prevalent coronary heart disease or heart failure who attended the Atherosclerosis Risk In the Community (ARIC) visit 5 examination (2011-2013) and underwent transthoracic echocardiography (age, 75±6 years; 61% women, 23% black). Subjects were grouped across the dysglycemia spectrum as normal (39%), pre-diabetes mellitus (31%), or diabetes mellitus (30%) based on medical history, antidiabetic medication use, and glycated hemoglobin levels. Glycemic status was related to measures of cardiac structure and function. Worsening dysglycemia was associated with increased left ventricular mass, worse diastolic function, and subtle reduction in left ventricular systolic function (P≤0.01 for all). For every 1% higher glycated hemoglobin, left ventricular mass was higher by 3.0 g (95% confidence interval, 1.5-4.6 g), E/E' by 0.5 (95% confidence interval, 0.4-0.7), and global longitudinal strain by 0.3% (95% confidence interval, 0.2-0.4) in multivariable analyses. In a large contemporary biracial cohort of elderly subjects without prevalent cardiovascular disease or heart failure, dysglycemia was associated with subtle and subclinical alterations of cardiac structure, and left ventricular systolic and diastolic function. It remains unclear whether these are sufficient to explain the heightened risk of heart failure in individuals with diabetes mellitus. © 2015 American Heart Association, Inc.
Wang, Ying-Chieh; Chen, Chun-Yu; Kuo, Terry B J; Lai, Ching-Jung; Yang, Cheryl C H
2012-06-01
Sudden cardiac death is higher among schizophrenic patients and is associated with parasympathetic hypoactivity. Antipsychotic agents are highly suspected to be a precipitating factor. Thus, we aimed to test if the antipsychotics haloperidol, risperidone and clozapine affect cardiac autonomic function, excluding the confounding effect of altered sleep structure by the drugs. In this study, haloperidol, risperidone and clozapine were given separately by intraperitoneal injection to male Wistar-Kyoto rats for 5 days. Electroencephalogram (EEG), electromyogram (EMG) and electrocardiographic signals were recorded at baseline and 5 days after drug treatments. Sleep scoring was based on EEG and EMG signals. Cardiac autonomic function was assessed using heart rate variability analysis. Clozapine increased heart rate and suppressed cardiac sympathetic and parasympathetic activity. Cardiac acceleration was more severe during sleep. Haloperidol tended to decrease heart rate while risperidone mildly increased heart rate; however, their effects were less obvious than those of clozapine. There was a significant drug-by-stage interaction on several heart rate variability measures. Taking this evidence as a whole, we conclude that haloperidol has a better level of cardiovascular safety than either risperidone or clozapine. Application of this approach to other psychotropic agents in the future will be a useful and helpful way to evaluate the cardiovascular safety of the various psychotropic medications that are in clinical use. Copyright © 2012 S. Karger AG, Basel.
Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease.
von Rhein, Michael; Buchmann, Andreas; Hagmann, Cornelia; Huber, Reto; Klaver, Peter; Knirsch, Walter; Latal, Beatrice
2014-01-01
Patients with complex congenital heart disease are at risk for neurodevelopmental impairments. Evidence suggests that brain maturation can be delayed and pre- and postoperative brain injury may occur, and there is limited information on the long-term effect of congenital heart disease on brain development and function in adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of childhood cardiopulmonary bypass surgery with no structural brain lesions evident through conventional cerebral magnetic resonance imaging and 32 healthy control subjects underwent extensive neurodevelopmental assessment and cerebral magnetic resonance imaging. Cerebral scans were analysed quantitatively using surface-based and voxel-based morphometry. Compared with control subjects, patients had lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different. Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11% (corpus callosum). Adolescents with cyanotic heart disease showed more brain volume loss than those with acyanotic heart disease, particularly in the white matter, thalami, hippocampi and corpus callosum (all P-values < 0.05). Brain volume reduction correlated significantly with cognitive, motor and executive functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest that there are long-lasting cerebral changes in adolescent survivors of cardiopulmonary bypass surgery for congenital heart disease and that these changes are associated with functional outcome.
Neurocognitive and executive functioning in adult survivors of congenital heart disease.
Klouda, Leda; Franklin, Wayne J; Saraf, Anita; Parekh, Dhaval R; Schwartz, David D
2017-01-01
Congenital heart disease (CHD) can affect the developing central nervous system, resulting in neurocognitive and behavioral deficits. Preoperative neurological abnormalities as well as sequelae of the open heart operations required to correct structural abnormalities of the heart contribute to these deficits. There are few studies examining the neurocognitive functioning of adults with CHD. This study sought to investigate multiple domains of neurocognitive functioning in adult survivors of CHD who had childhood cardiac surgery with either moderate or severe disease complexity. A total of 48 adults (18-49 years of age) who had undergone cardiac surgery for CHD prior to five years of age participated in the study. CHD severity was classified as moderate or severe according to the 32nd Bethesda Guidelines. A computerized battery of standardized neurocognitive tests (CNS-Vital Signs), a validated rating scale of executive functioning, and demographic questionnaires were administered. There were no significant differences between the moderate CHD group and normative data on any cognitive measure. In contrast, the severe CHD group differed from norms in multiple domains: psychomotor speed, processing speed, complex attention, reaction time, and on the overall neurocognitive index. Number of surgeries was strongly related to worse executive functioning. There was no association between age at first surgery or time since last surgery and neuropsychological functioning. Number of surgeries was also unrelated to neurocognitive test performance. Patients with severe CHD performed significantly worse on measures of processing speed, attention, and executive functioning. These findings may be useful in the long-term care of adults with congenital heart disease. © 2016 Wiley Periodicals, Inc.
Anisimov, Sergey V; Khavinson, Vladimir Kh; Anisimov, Vladimir N
2004-01-01
Aging is associated with significant alterations in gene expression in numerous organs and tissues. Anti-aging therapy with peptide bioregulators holds much promise for the correction of age-associated changes, making a screening for their molecular targets in tissues an important question of modern gerontology. The synthetic tetrapeptide Cortagen (Ala-Glu-Asp-Pro) was obtained by directed synthesis based on amino acid analysis of natural brain cortex peptide preparation Cortexin. In humans, Cortagen demonstrated a pronounced therapeutic effect upon the structural and functional posttraumatic recovery of peripheral nerve tissue. Importantly, other effects were also observed in cardiovascular and cerebrovascular parameters. Based on these latter observations, we hypothesized that acute course of Cortagen treatment, large-scale transcriptome analysis, and identification of transcripts with altered expression in heart would facilitate our understanding of the mechanisms responsible for this peptide biological effects. We therefore analyzed the expression of 15,247 transcripts in the heart of female 6-months CBA mice receiving injections of Cortagen for 5 consecutive days was studied by cDNA microarrays. Comparative analysis of cDNA microarray hybridisation with heart samples from control and experimental group revealed 234 clones (1,53% of the total number of clones) with significant changes of expression that matched 110 known genes belonging to various functional categories. Maximum up- and down-regulation was +5.42 and -2.86, respectively. Intercomparison of changes in cardiac expression profile induced by synthetic peptides (Cortagen, Vilon, Epitalon) and pineal peptide hormone melatonin revealed both common and specific effects of Cortagen upon gene expression in heart.
Raj, Manu; Paul, Mary; Sudhakar, Abish; Varghese, Anu Alphonse; Haridas, Aareesh Chittulliparamb; Kabali, Conrad; Kumar, Raman Krishna
2015-01-01
The microeconomic impact of surgery for congenital heart disease is unexplored, particularly in resource limited environments. We sought to understand the direct and indirect costs related to congenital heart surgery and its impact on Indian households from a family perspective. Baseline and first follow-up data of 644 consecutive children admitted for surgery for congenital heart disease (March 2013 - July 2014) in a tertiary referral hospital in Central Kerala, South India was collected prospectivelyfrom parents through questionnaires using a semi-structured interview schedule. The median age was 8.2 months (IQR: 3.0- 36.0 months). Most families belonged to upper middle (43.0%) and lower middle (35.7%) socioeconomic class. Only 3.9% of families had some form of health insurance. The median expense for the admission and surgery was INR 201898 (IQR: 163287-266139) [I$ 11989 (IQR: 9696-15804)], which was 0.93 (IQR: 0.52-1.49) times the annual family income of affected patients. Median loss of man-days was 35 (IQR: 24-50) and job-days was 15 (IQR: 11-24). Surgical risk category and hospital stay duration significantly predicted higher costs. One in two families reported overwhelming to high financial stress during admission period for surgery. Approximately half of the families borrowed money during the follow up period after surgery. Surgery for congenital heart disease results in significant financial burden for majority of families studied. Efforts should be directed at further reductions in treatment costs without compromising the quality of care together with generating financial support for affected families.
Costello, John P; Olivieri, Laura J; Krieger, Axel; Thabit, Omar; Marshall, M Blair; Yoo, Shi-Joon; Kim, Peter C; Jonas, Richard A; Nath, Dilip S
2014-07-01
The current educational approach for teaching congenital heart disease (CHD) anatomy to students involves instructional tools and techniques that have significant limitations. This study sought to assess the feasibility of utilizing present-day three-dimensional (3D) printing technology to create high-fidelity synthetic heart models with ventricular septal defect (VSD) lesions and applying these models to a novel, simulation-based educational curriculum for premedical and medical students. Archived, de-identified magnetic resonance images of five common VSD subtypes were obtained. These cardiac images were then segmented and built into 3D computer-aided design models using Mimics Innovation Suite software. An Objet500 Connex 3D printer was subsequently utilized to print a high-fidelity heart model for each VSD subtype. Next, a simulation-based educational curriculum using these heart models was developed and implemented in the instruction of 29 premedical and medical students. Assessment of this curriculum was undertaken with Likert-type questionnaires. High-fidelity VSD models were successfully created utilizing magnetic resonance imaging data and 3D printing. Following instruction with these high-fidelity models, all students reported significant improvement in knowledge acquisition (P < .0001), knowledge reporting (P < .0001), and structural conceptualization (P < .0001) of VSDs. It is feasible to use present-day 3D printing technology to create high-fidelity heart models with complex intracardiac defects. Furthermore, this tool forms the foundation for an innovative, simulation-based educational approach to teach students about CHD and creates a novel opportunity to stimulate their interest in this field. © The Author(s) 2014.
Taneike, Manabu; Nishida, Kazuhiko; Omiya, Shigemiki; Zarrinpashneh, Elham; Misaka, Tomofumi; Kitazume-Taneike, Rika; Austin, Ruth; Takaoka, Minoru; Yamaguchi, Osamu; Gambello, Michael J.; Shah, Ajay M.; Otsu, Kinya
2016-01-01
Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth, proliferation and metabolism. mTORC1 regulates protein synthesis positively and autophagy negatively. Autophagy is a major system to manage bulk degradation and recycling of cytoplasmic components and organelles. Tuberous sclerosis complex (TSC) 1 and 2 form a heterodimeric complex and inactivate Ras homolog enriched in brain, resulting in inhibition of mTORC1. Here, we investigated the effects of hyperactivation of mTORC1 on cardiac function and structure using cardiac-specific TSC2-deficient (TSC2-/-) mice. TSC2-/- mice were born normally at the expected Mendelian ratio. However, the median life span of TSC2-/- mice was approximately 10 months and significantly shorter than that of control mice. TSC2-/- mice showed cardiac dysfunction and cardiomyocyte hypertrophy without considerable fibrosis, cell infiltration or apoptotic cardiomyocyte death. Ultrastructural analysis of TSC2-/- hearts revealed misalignment, aggregation and a decrease in the size and an increase in the number of mitochondria, but the mitochondrial function was maintained. Autophagic flux was inhibited, while the phosphorylation level of S6 or eukaryotic initiation factor 4E -binding protein 1, downstream of mTORC1, was increased. The upregulation of autophagic flux by trehalose treatment attenuated the cardiac phenotypes such as cardiac dysfunction and structural abnormalities of mitochondria in TSC2-/- hearts. The results suggest that autophagy via the TSC2-mTORC1 signaling pathway plays an important role in maintenance of cardiac function and mitochondrial quantity and size in the heart and could be a therapeutic target to maintain mitochondrial homeostasis in failing hearts. PMID:27023784
Velagaleti, Raghava S; Gona, Philimon; Chuang, Michael L; Salton, Carol J; Fox, Caroline S; Blease, Susan J; Yeon, Susan B; Manning, Warren J; O'Donnell, Christopher J
2010-05-01
Data regarding the relationships of diabetes, insulin resistance, and subclinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations. A total of 1603 Framingham Heart Study Offspring participants (age, 64+/-9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction, cardiac output, and left atrial size. Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, prediabetes, and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hour insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht(2.7) and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with prediabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable adjustment only in men. LVM/LVEDV was significantly associated with 2-hour insulin in men only, and RWT was significantly associated with 2-hour glucose in women only. In multivariable stepwise selection analyses, the inclusion of body mass index led to a loss in statistical significance. Although insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling.
Velagaleti, Raghava S.; Gona, Philimon; Chuang, Michael L.; Salton, Carol J.; Fox, Caroline S.; Blease, Susan J.; Yeon, Susan B.; Manning, Warren J.; O’Donnell, Christopher J.
2011-01-01
Background Data regarding the relationships of diabetes, insulin resistance and sub-clinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations. Methods and Results A total of 1603 Framingham Heart Study Offspring participants (age 64±9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction (EF), cardiac output (CO) and left atrial size (LAD). Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, pre-diabetes and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hr insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht2.7 and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with pre-diabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable-adjustment only in men. LVM/LVEDV was significantly associated with 2-hr insulin in men only, and RWT was significantly associated with 2-hr glucose in women only. In multivariable stepwise selection analyses, the inclusion of BMI led to a loss in statistical significance. Conclusions While insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling. PMID:20208015
Folsom, Aaron R; Shah, Amil M; Lutsey, Pamela L; Roetker, Nicholas S; Alonso, Alvaro; Avery, Christy L; Miedema, Michael D; Konety, Suma; Chang, Patricia P; Solomon, Scott D
2015-09-01
Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines—on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose—is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. One in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. Greater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. Copyright © 2015 Elsevier Inc. All rights reserved.
Klein, L S; Shih, H T; Hackett, F K; Zipes, D P; Miles, W M
1992-05-01
Radiofrequency energy has been used safely and successfully to eliminate accessory pathways in patients with the Wolff-Parkinson-White syndrome and the substrate for atrioventricular nodal reentrant tachycardia. However, this form of ablation has had only limited success in eliminating ventricular tachycardia in patients with structural heart disease. In contrast, direct-current catheter ablation has been used successfully to eliminate ventricular tachycardia in patients with and without structural heart disease. The purpose of this study was to test whether radiofrequency energy can safely and effectively ablate ventricular tachycardia in patients without structural heart disease. Sixteen patients (nine women and seven men; mean age, 38 years; range, 18-55 years) without structural heart disease who had ventricular tachycardia underwent radiofrequency catheter ablation to eliminate the ventricular tachycardia. Two patients presented with syncope, nine with presyncope, and five with palpitations only. Mean duration of symptoms was 6.7 years (range, 0.5-20 years). Radiofrequency catheter ablation successfully eliminated ventricular tachycardia in 15 of 16 patients (94%). Sites of ventricular tachycardia origin included the high right ventricular outflow tract (12 patients), the right ventricular septum near the tricuspid valve (three patients), and the left ventricular septum (one patient). The only ablation failure was in a patient whose ventricular tachycardia arose from a region near the His bundle. An accurate pace map, early local endocardial activation, and firm catheter contact with endocardium were associated with successful ablation. Radiofrequency ablation did not cause arrhythmias, produced minimal cardiac enzyme rise, and resulted in no detectable change in cardiac function by Doppler echocardiography. Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease is effective and safe and may be considered as early therapy in these patients.
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.
The day/night proteome in the murine heart.
Podobed, Peter; Pyle, W Glen; Ackloo, Suzanne; Alibhai, Faisal J; Tsimakouridze, Elena V; Ratcliffe, William F; Mackay, Allison; Simpson, Jeremy; Wright, David C; Kirby, Gordon M; Young, Martin E; Martino, Tami A
2014-07-15
Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function.
The day/night proteome in the murine heart
Podobed, Peter; Pyle, W. Glen; Ackloo, Suzanne; Alibhai, Faisal J.; Tsimakouridze, Elena V.; Ratcliffe, William F.; Mackay, Allison; Simpson, Jeremy; Wright, David C.; Kirby, Gordon M.; Young, Martin E.
2014-01-01
Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function. PMID:24789993
Olejník, Peter; Nosal, Matej; Havran, Tomas; Furdova, Adriana; Cizmar, Maros; Slabej, Michal; Thurzo, Andrej; Vitovic, Pavol; Klvac, Martin; Acel, Tibor; Masura, Jozef
2017-01-01
To evaluate the accuracy of the three-dimensional (3D) printing of cardiovascular structures. To explore whether utilisation of 3D printed heart replicas can improve surgical and catheter interventional planning in patients with complex congenital heart defects. Between December 2014 and November 2015 we fabricated eight cardiovascular models based on computed tomography data in patients with complex spatial anatomical relationships of cardiovascular structures. A Bland-Altman analysis was used to assess the accuracy of 3D printing by comparing dimension measurements at analogous anatomical locations between the printed models and digital imagery data, as well as between printed models and in vivo surgical findings. The contribution of 3D printed heart models for perioperative planning improvement was evaluated in the four most representative patients. Bland-Altman analysis confirmed the high accuracy of 3D cardiovascular printing. Each printed model offered an improved spatial anatomical orientation of cardiovascular structures. Current 3D printers can produce authentic copies of patients` cardiovascular systems from computed tomography data. The use of 3D printed models can facilitate surgical or catheter interventional procedures in patients with complex congenital heart defects due to better preoperative planning and intraoperative orientation.
Einstein, Daniel R.; Del Pin, Facundo; Jiao, Xiangmin; Kuprat, Andrew P.; Carson, James P.; Kunzelman, Karyn S.; Cochran, Richard P.; Guccione, Julius M.; Ratcliffe, Mark B.
2009-01-01
SUMMARY The remodeling that occurs after a posterolateral myocardial infarction can alter mitral valve function by creating conformational abnormalities in the mitral annulus and in the posteromedial papillary muscle, leading to mitral regurgitation (MR). It is generally assumed that this remodeling is caused by a volume load and is mediated by an increase in diastolic wall stress. Thus, mitral regurgitation can be both the cause and effect of an abnormal cardiac stress environment. Computational modeling of ischemic MR and its surgical correction is attractive because it enables an examination of whether a given intervention addresses the correction of regurgitation (fluid-flow) at the cost of abnormal tissue stress. This is significant because the negative effects of an increased wall stress due to the intervention will only be evident over time. However, a meaningful fluid-structure interaction model of the left heart is not trivial; it requires a careful characterization of the in-vivo cardiac geometry, tissue parameterization though inverse analysis, a robust coupled solver that handles collapsing Lagrangian interfaces, automatic grid-generation algorithms that are capable of accurately discretizing the cardiac geometry, innovations in image analysis, competent and efficient constitutive models and an understanding of the spatial organization of tissue microstructure. In this manuscript, we profile our work toward a comprehensive fluid-structure interaction model of the left heart by reviewing our early work, presenting our current work and laying out our future work in four broad categories: data collection, geometry, fluid-structure interaction and validation. PMID:20454531
Functional significance of cardiac reinnervation in heart transplant recipients.
Schwaiblmair, M; von Scheidt, W; Uberfuhr, P; Ziegler, S; Schwaiger, M; Reichart, B; Vogelmeier, C
1999-09-01
There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p < .05). In transplant recipients with reinnervation, heart rate at maximum exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an improved oxygen delivery to the exercising muscles and a reduced ventilation-perfusion mismatching.
Parto, Parham; Lavie, Carl J; Arena, Ross; Bond, Samantha; Popovic, Dejana; Ventura, Hector O
2016-11-01
The prevalence of obesity among adults and children worldwide has reached epic proportions and has become a major independent risk factor for the development of heart failure (HF), in addition to a contributor of hypertension and cardiovascular disease. The implications of obesity in the development of HF involve adverse effects on cardiac structure and function. Despite all of this, in the setting of chronic HF, excess body mass is associated with improved clinical outcomes, demonstrating the presence of an obesity paradox. In this review, we will discuss the gender differences, global application, potential mechanisms and role of interventions based on fitness and purposeful weight loss as potential therapeutic strategies.
Abnormal mitochondrial respiration in failed human myocardium.
Sharov, V G; Todor, A V; Silverman, N; Goldstein, S; Sabbah, H N
2000-12-01
Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n=9) or idiopathic dilated (IDC, n=9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON). Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V(SUB)), state 3 respiration (after addition of ADP, V(ADP)) and respiration after the addition of atractyloside (V(AT)) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V(ADP)was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V(ADP)/V(AT), was also significantly decreased in HF compared to CON. In both ICM and IDC, V(ADP)was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance. Copyright 2000 Academic Press.
NASA Astrophysics Data System (ADS)
Kwon, M. R.; Park, T. H.; Lee, T. H.; Lee, B. R.; Kim, T. G.
2018-04-01
We propose a design for highly efficient AlGaN-based deep-ultraviolet light-emitting diodes (DUV LEDs) using a heart-shaped graded Al composition electron-blocking layer (EBL). This novel structure reduced downward band bending at the interface between the last quantum barrier and the EBL and flattened the electrostatic field in the interlayer between the barriers of the multi-quantum barrier EBL. Consequently, electron leakage was significantly suppressed and hole injection efficiency was found to have improved. The parameter values of simulation were extracted from the experimental data of the reference DUV LEDs. Using the SimuLED, we compared the electrical and optical properties of three structures with different Al compositions in the active region and the EBL. The internal quantum efficiency of the proposed structure was shown to exceed those of the reference DUV LEDs by a factor of 1.9. Additionally, the output power at 20 mA was found to increase by a factor of 2.1.
Zhang, Xuemeng; Kampourakis, Thomas; Yan, Ziqian; Sevrieva, Ivanka; Irving, Malcolm; Sun, Yin-Biao
2017-02-23
The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the underlying molecular mechanism remains unknown. We applied a fluorescence-based method, which reports structural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that mechanism. The distinct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the thick filaments allowed us to identify two aspects of the Frank-Starling relation. Our results show that the enhanced force observed when heart muscle cells are maximally activated by calcium is due to a change in thick filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in thin filament structure.
Walker, Andrew Mn; Patel, Peysh A; Rajwani, Adil; Groves, David; Denby, Christine; Kearney, Lorraine; Sapsford, Robert J; Witte, Klaus K; Kearney, Mark T; Cubbon, Richard M
2016-09-01
Diabetes mellitus is associated with an increased risk of death and hospitalisation in patients with chronic heart failure. Better understanding of potential underlying mechanisms may aid the development of diabetes mellitus-specific chronic heart failure therapeutic strategies. Prospective observational cohort study of 628 patients with chronic heart failure associated with left ventricular systolic dysfunction receiving contemporary evidence-based therapy. Indices of cardiac structure and function, along with symptoms and biochemical parameters, were compared in patients with and without diabetes mellitus at study recruitment and 1 year later. Patients with diabetes mellitus (24.2%) experienced higher rates of all-cause [hazard ratio, 2.3 (95% confidence interval, 1.8-3.0)] and chronic heart failure-specific mortality and hospitalisation despite comparable pharmacological and device-based therapies. At study recruitment, patients with diabetes mellitus were more symptomatic, required greater diuretic doses and more frequently had radiologic evidence of pulmonary oedema, despite higher left ventricular ejection fraction. They also exhibited echocardiographic evidence of increased left ventricular wall thickness and pulmonary arterial pressure. Diabetes mellitus was associated with reduced indices of heart rate variability and increased heart rate turbulence. During follow-up, patients with diabetes mellitus experienced less beneficial left ventricular remodelling and greater deterioration in renal function. Diabetes mellitus is associated with features of adverse structural and functional cardiac remodelling in patients with chronic heart failure. © The Author(s) 2016.
Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure.
Guo, Cathy A; Guo, Shaodong
2017-06-01
The heart is an insulin-dependent and energy-consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth and survival. Heart failure is highly associated with insulin resistance, and heart failure patients suffer from the cardiac energy deficiency and structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics and impairing cardiac contractility. Recent studies demonstrated that insulin receptor substrates 1 and 2 (IRS-1,-2) are major mediators of both insulin and insulin-like growth factor-1 (IGF-1) signaling responsible for myocardial energetics, structure, function and organismal survival. Importantly, the insulin receptor substrates (IRS) play an important role in the activation of the phosphatidylinositide-3-dependent kinase (PI-3K) that controls Akt and Foxo1 signaling cascade, regulating the mitochondrial function, cardiac energy metabolism and the renin-angiotensin system. Dysregulation of this branch in signaling cascades by insulin resistance in the heart through the endocrine system promotes heart failure, providing a novel mechanism for diabetic cardiomyopathy. Therefore, targeting this branch of IRS→PI-3K→Foxo1 signaling cascade and associated pathways may provide a fundamental strategy for the therapeutic and nutritional development in control of metabolic and cardiovascular diseases. In this review, we focus on insulin signaling and resistance in the heart and the role energetics play in cardiac metabolism, structure and function. © 2017 Society for Endocrinology.
NASA Astrophysics Data System (ADS)
Cleland, Timothy P.; Stoskopf, Michael K.; Schweitzer, Mary H.
2011-03-01
A three-dimensional, iron-cemented structure found in the anterior thoracic cavity of articulated Thescelosaurus skeletal remains was hypothesized to be the fossilized remains of the animal's four-chambered heart. This was important because the finding could be interpreted to support a hypothesis that non-avian dinosaurs were endothermic. Mammals and birds, the only extant organisms with four-chambered hearts and single aortae, are endotherms. The hypothesis that this Thescelosaurus has a preserved heart was controversial, and therefore, we reexamined it using higher-resolution computed tomography, paleohistological examination, X-ray diffraction analysis, X-ray photoelectron spectroscopy, and scanning electron microscopy. This suite of analyses allows for detailed morphological and chemical examination beyond what was provided in the original work. Neither the more detailed examination of the gross morphology and orientation of the thoracic "heart" nor the microstructural studies supported the hypothesis that the structure was a heart. The more advanced computed tomography showed the same three areas of low density as the earlier studies with no evidence of additional low-density areas as might be expected from examinations of an ex situ ostrich heart. Microstructural examination of a fragment taken from the "heart" was consistent with cemented sand grains, and no chemical signal consistent with a biological origin was detected. However, small patches of cell-like microstructures were preserved in the sandstone matrix of the thoracic structure. A possible biological origin for these microstructures is the focus of ongoing investigation.
Kötter, Thomas; Bartel, Carmen; Schramm, Susanne; Lange, Petra; Höfer, Eva; Hänsel, Michaela; Waffenschmidt, Siw; Waldt, Susanne Ein; Hoffmann-Eßer, Wiebke; Rüther, Alric; Lühmann, Dagmar; Scherer, Martin
2013-01-01
Disease Management Programmes (DMPs) are structured treatment programmes for chronic diseases. The DMP requirements are primarily derived from evidence-based guidelines. DMPs are regularly revised to ensure that they reflect current best practice and medical knowledge. The aim of this study was to assess the need for updating the German DMP module on heart failure by comparing it to relevant guidelines and identifying recommendations that should be revised. We systematically searched for clinical guidelines on heart failure published in German, English or French, and extracted relevant guideline recommendations. All included guidelines were assessed for methodological quality. To identify revision needs in the DMP, we performed a synoptic analysis of the extracted guideline recommendations and DMP requirements. 27 guidelines were included. The extracted recommendations covered all aspects of the management of heart failure. The comparison of guideline recommendations with DMP requirements showed that, overall, guideline recommendations were more detailed than DMP requirements, and that the guidelines covered topics not included in the DMP module. The DMP module is largely consistent with current guidelines on heart failure. We did not identify any need for significant revision of the DMP requirements. However, some specific recommendations of the DMP module could benefit from revision. Copyright © 2013. Published by Elsevier GmbH.
Cone beam computed tomography of plastinated hearts for instruction of radiological anatomy.
Chang, Chih-Wei; Atkinson, Gregory; Gandhi, Niket; Farrell, Michael L; Labrash, Steven; Smith, Alice B; Norton, Neil S; Matsui, Takashi; Lozanoff, Scott
2016-09-01
Radiological anatomy education is an important aspect of the medical curriculum. The purpose of this study was to establish and demonstrate the use of plastinated anatomical specimens, specifically human hearts, for use in radiological anatomy education. Four human hearts were processed with routine plastination procedures at room temperature. Specimens were subjected to cone beam computed tomography and a graphics program (ER3D) was applied to generate 3D cardiac models. A comparison was conducted between plastinated hearts and their corresponding computer models based on a list of morphological cardiac features commonly studied in the gross anatomy laboratory. Results showed significant correspondence between plastinations and CBCT-generated 3D models (98 %; p < .01) for external structures and 100 % for internal cardiac features, while 85 % correspondence was achieved between plastinations and 2D CBCT slices. Complete correspondence (100 %) was achieved between key observations on the plastinations and internal radiological findings typically required of medical student. All pathologic features seen on the plastinated hearts were also visualized internally with the CBCT-generated models and 2D slices. These results suggest that CBCT-derived slices and models can be successfully generated from plastinated material and provide accurate representations for radiological anatomy education.
2014-02-25
risk of drug or alcohol abuse. In addition, patients with PTSD often display structural changes in the pre- frontal cortex, the amygdala, and the... triglyceride levels (12–15). An 1871 report noted that serious cardiac disorders (car- diomyopathies, heart failure, heart pain, etc.) were a consequence of...epicardium probably play a key role in the EMT process (30, 31). Maintaining the proper ECM structure is critical to pre- serving the architecture and
Moses, Monday Omoniyi; Osei, Francis; Appiah, Eric Juniour; Obour, Agnes; Akwa, Lady Gwendoline; Baffour-Awuah, Biggie; Asamoah, Benjamin; Sarpong, Peter Akwasi; Adams, Caleb; D’Onofrio, Rosario
2017-01-01
This study examined and compared, based on year of study and gender, the health and performance indices of university undergraduate students. Eighty-nine students (mean±standard deviation age, 22.47±2.22 years) were randomly selected for assessment prior to second semester examination of 2015/2016 academic year. body mass index, resting metabolic rate, visceral fat, skeletal muscle mass, body fat, systolic & diastolic blood pressure, resting heart rate, upper & lower body endurance, handgrip strength, and lower back and hamstring flexibility were assessed. The students had sedentary heart rate, low skeletal muscle mass, average upper and lower body endurance, and weak handgrip strength. Significant difference existed in the visceral fat (P=0.008) between third and fourth year students. There were significant gender differences in resting metabolic rate (P=0.000), skeletal muscle mass (P=0.000), body fat (P=0.000), systolic blood pressure (P=0.001), heart rate (P=0.005) and handgrip strength (P=0.000). There are gender differences in association between health and performance indices. Dependable health education and pragmatic involvement of undergraduate university students in structured exercise programmes are recommended. PMID:29114505
Dynamic correlations between heart and brain rhythm during Autogenic meditation
Kim, Dae-Keun; Lee, Kyung-Mi; Kim, Jongwha; Whang, Min-Cheol; Kang, Seung Wan
2013-01-01
This study is aimed to determine significant physiological parameters of brain and heart under meditative state, both in each activities and their dynamic correlations. Electrophysiological changes in response to meditation were explored in 12 healthy volunteers who completed 8 weeks of a basic training course in autogenic meditation. Heart coherence, representing the degree of ordering in oscillation of heart rhythm intervals, increased significantly during meditation. Relative EEG alpha power and alpha lagged coherence also increased. A significant slowing of parietal peak alpha frequency was observed. Parietal peak alpha power increased with increasing heart coherence during meditation, but no such relationship was observed during baseline. Average alpha lagged coherence also increased with increasing heart coherence during meditation, but weak opposite relationship was observed at baseline. Relative alpha power increased with increasing heart coherence during both meditation and baseline periods. Heart coherence can be a cardiac marker for the meditative state and also may be a general marker for the meditative state since heart coherence is strongly correlated with EEG alpha activities. It is expected that increasing heart coherence and the accompanying EEG alpha activations, heart brain synchronicity, would help recover physiological synchrony following a period of homeostatic depletion. PMID:23914165
Dynamic correlations between heart and brain rhythm during Autogenic meditation.
Kim, Dae-Keun; Lee, Kyung-Mi; Kim, Jongwha; Whang, Min-Cheol; Kang, Seung Wan
2013-01-01
This study is aimed to determine significant physiological parameters of brain and heart under meditative state, both in each activities and their dynamic correlations. Electrophysiological changes in response to meditation were explored in 12 healthy volunteers who completed 8 weeks of a basic training course in autogenic meditation. Heart coherence, representing the degree of ordering in oscillation of heart rhythm intervals, increased significantly during meditation. Relative EEG alpha power and alpha lagged coherence also increased. A significant slowing of parietal peak alpha frequency was observed. Parietal peak alpha power increased with increasing heart coherence during meditation, but no such relationship was observed during baseline. Average alpha lagged coherence also increased with increasing heart coherence during meditation, but weak opposite relationship was observed at baseline. Relative alpha power increased with increasing heart coherence during both meditation and baseline periods. Heart coherence can be a cardiac marker for the meditative state and also may be a general marker for the meditative state since heart coherence is strongly correlated with EEG alpha activities. It is expected that increasing heart coherence and the accompanying EEG alpha activations, heart brain synchronicity, would help recover physiological synchrony following a period of homeostatic depletion.
NASA Astrophysics Data System (ADS)
Ma, Pei; Gu, Shi; Wang, Yves T.; Jenkins, Michael W.; Rollins, Andrew M.
2016-03-01
Optical mapping (OM) using fluorescent voltage-sensitive dyes (VSD) to measure membrane potential is currently the most effective method for electrophysiology studies in early embryonic hearts due to its noninvasiveness and large field-of-view. Conventional OM acquires bright-field images, collecting signals that are integrated in depth and projected onto a 2D plane, not capturing the 3D structure of the sample. Early embryonic hearts, especially at looping stages, have a complicated, tubular geometry. Therefore, conventional OM cannot provide a full picture of the electrical conduction circumferentially around the heart, and may result in incomplete and inaccurate measurements. Here, we demonstrate OM of Hamburger and Hamilton stage 14 embryonic quail hearts using a new commercially-available VSD, Fluovolt, and depth sectioning using a custom built light-sheet microscopy system. Axial and lateral resolution of the system is 14µm and 8µm respectively. For OM imaging, the field-of-view was set to 900µm×900µm to cover the entire heart. 2D over time OM image sets at multiple cross-sections through the looping-stage heart were recorded. The shapes of both atrial and ventricular action potentials acquired were consistent with previous reports using conventional VSD (di-4-ANNEPS). With Fluovolt, signal-to-noise ratio (SNR) is improved significantly by a factor of 2-10 (compared with di-4-ANNEPS) enabling light-sheet OM, which intrinsically has lower SNR due to smaller sampling volumes. Electrophysiologic parameters are rate dependent. Optical pacing was successfully integrated into the system to ensure heart rate consistency. This will also enable accurately gated reconstruction of full four dimensional conduction maps and 3D conduction velocity measurements.
Immunostaining of dissected zebrafish embryonic heart.
Yang, Jingchun; Xu, Xiaolei
2012-01-10
Zebrafish embryo becomes a popular in vivo vertebrate model for studying cardiac development and human heart diseases due to its advantageous embryology and genetics. About 100-200 embryos are readily available every week from a single pair of adult fish. The transparent embryos that develop ex utero make them ideal for assessing cardiac defects. The expression of any gene can be manipulated via morpholino technology or RNA injection. Moreover, forward genetic screens have already generated a list of mutants that affect different perspectives of cardiogenesis. Whole mount immunostaining is an important technique in this animal model to reveal the expression pattern of the targeted protein to a particular tissue. However, high resolution images that can reveal cellular or subcellular structures have been difficult, mainly due to the physical location of the heart and the poor penetration of the antibodies. Here, we present a method to address these bottlenecks by dissecting heart first and then conducting the staining process on the surface of a microscope slide. To prevent the loss of small heart samples and to facilitate solution handling, we restricted the heart samples within a circle on the surface of the microscope slides drawn by an immEdge pen. After the staining, the fluorescence signals can be directly observed by a compound microscope. Our new method significantly improves the penetration for antibodies, since a heart from an embryonic fish only consists of few cell layers. High quality images from intact hearts can be obtained within a much reduced procession time for zebrafish embryos aged from day 2 to day 6. Our method can be potentially extended to stain other organs dissected from either zebrafish or other small animals. Copyright © 2012 Journal of Visualized Experiments
Vaillant, Fanny; Magat, Julie; Bour, Pierre; Naulin, Jérôme; Benoist, David; Loyer, Virginie; Vieillot, Delphine; Labrousse, Louis; Ritter, Philippe; Bernus, Olivier; Dos Santos, Pierre; Quesson, Bruno
2016-05-15
To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications. Copyright © 2016 the American Physiological Society.
Li, Lei; Lin, Cheng-Ren; Ren, Jian-Xun; Miao, Lan; Yao, Ming-Jiang; Li, Dan; Shi, Yue; Ma, Yan-Lei; Fu, Jian-Hua; Liu, Jian-Xun
2014-02-01
To evaluate that the effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. Totally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Danlou tablet group, and Tanyu Tonzhi Fang(TYTZ) groups with doses of 2. 0, 1. 0 and 0. 5 g kg-1, with six in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome. After the operation, they were administered with drugs for 8 weeks. The changes in the myocardial ischemia were observed. The changes in the cardiac function and structure were detected by cardiac ultrasound and noninvasive hemodynamic method. Compared with the normal control group, the model group showed significant increase in myocardial ischemia and SVR and obvious decrease in CO, SV and LCW in noninvasive hemodynamic parameters (P <0.05 or P <0.01). The ultrasonic cardiogram indicated notable decrease in IVSd, LVPWs, EF and FS, and remarkable increase in LVIDs (P<0. 05 orP<0.01). Compared with the model group, TYTZ could reduce the myocardial ischemia, strengthen cardiac function, and improve the abnormal cardiac structure and function induced by ischemia (P <0. 05 or P <0. 01). TYTZ shows a significant effect in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. The clinical cardiac function detection method could be adopted to correctly evaluate the changes in the post-myocardial ischemia cardiac function, and narrow the gap between clinical application and basic experimental studies.
lncRNA Structure: Message to the Heart.
Fazal, Furqan M; Chang, Howard Y
2016-10-06
In this issue, Xue et al. (2016) describe the secondary structure of the heart-specific long non-coding RNA Braveheart, leading to the discovery of a short, asymmetric G-rich loop that controls cardiac lineage commitment by interacting with the transcription factor CNBP. Copyright © 2016 Elsevier Inc. All rights reserved.
History of cardiac anatomy: a comprehensive review from the Egyptians to today.
Loukas, Marios; Youssef, Pamela; Gielecki, Jerzy; Walocha, Jerzy; Natsis, Kostantinos; Tubbs, R Shane
2016-04-01
The nature, function, and anatomy of the heart have been extensively studied since 3500 B.C. Greek and Egyptian science developed a basic understanding of the heart, although this was primarily related to religious beliefs. During the Hippocratic era, Hippocrates and his colleagues developed a more scientific and less religious understanding of the cardiovascular system. The post-Hippocratic era was characterized by more advanced descriptions of the location, structure, and function of the heart. The Alexandrian, Roman, Medieval Islamic, and European eras included turning points in the history of cardiac anatomy. Subsequently, after the structure and function of the heart were established, its connection with the lungs was investigated. Description of the pulmonary circulation was followed by the discovery of the conductive system and innervation of the heart. © 2016 Wiley Periodicals, Inc.
Zhou, Zhengfang; Wang, Jingying; Guo, Chaoshe; Chang, Weiting; Zhuang, Jian; Zhu, Ping; Li, Xue
2017-01-24
The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors. Six2-positive (Six2 + ) progenitors are rapidly recruited and assigned, and their descendants are allocated successively to regions of the heart from the right ventricle (RV) to the pulmonary trunk. Global ablation of Six2 + progenitors resulted in RV hypoplasia and pulmonary atresia. An early stage-specific ablation of a small subset of Six2 + progenitors did not cause any apparent structural defect at birth but rather resulted in adult-onset cardiac hypertrophy and dysfunction. Furthermore, Six2 expression depends in part on Shh signaling, and Shh deletion resulted in severe deficiency of Six2 + progenitors. Collectively, these findings unveil the chronological features of cardiogenesis, in which the mammalian heart is built sequentially by temporally distinct populations of cardiac progenitors, and provide insights into late-onset congenital heart disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Inhibition of Autoimmune Chagas-Like Heart Disease by Bone Marrow Transplantation
Guimaro, Maria C.; Alves, Rozeneide M.; Rose, Ester; Sousa, Alessandro O.; de Cássia Rosa, Ana; Hecht, Mariana M.; Sousa, Marcelo V.; Andrade, Rafael R.; Vital, Tamires; Plachy, Jiří; Nitz, Nadjar; Hejnar, Jiří; Gomes, Clever C.; L. Teixeira, Antonio R.
2014-01-01
Background Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. Methods/Principal Findings To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts. Conclusions/Significance Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease. PMID:25521296
Information Theory to Probe Intrapartum Fetal Heart Rate Dynamics
NASA Astrophysics Data System (ADS)
Granero-Belinchon, Carlos; Roux, Stéphane; Abry, Patrice; Doret, Muriel; Garnier, Nicolas
2017-11-01
Intrapartum fetal heart rate (FHR) monitoring constitutes a reference tool in clinical practice to assess the baby health status and to detect fetal acidosis. It is usually analyzed by visual inspection grounded on FIGO criteria. Characterization of Intrapartum fetal heart rate temporal dynamics remains a challenging task and continuously receives academic research efforts. Complexity measures, often implemented with tools referred to as \\emph{Approximate Entropy} (ApEn) or \\emph{Sample Entropy} (SampEn), have regularly been reported as significant features for intrapartum FHR analysis. We explore how Information Theory, and especially {\\em auto mutual information} (AMI), is connected to ApEn and SampEn and can be used to probe FHR dynamics. Applied to a large (1404 subjects) and documented database of FHR data, collected in a French academic hospital, it is shown that i) auto mutual information outperforms ApEn and SampEn for acidosis detection in the first stage of labor and continues to yield the best performance in the second stage; ii) Shannon entropy increases as labor progresses, and is always much larger in the second stage;iii) babies suffering from fetal acidosis additionally show more structured temporal dynamics than healthy ones and that this progressive structuration can be used for early acidosis detection.
Rudin-Bitterli, Tabitha S; Spicer, John I; Rundle, Simon D
2016-04-01
Physiological plasticity of early developmental stages is a key way by which organisms can survive and adapt to environmental change. We investigated developmental plasticity of aspects of the cardio-respiratory physiology of encapsulated embryos of a marine gastropod, Littorina obtusata, surviving exposure to moderate hypoxia (PO2 =8 kPa) and compared the development of these survivors with that of individuals that died before hatching. Individuals surviving hypoxia exhibited a slower rate of development and altered ontogeny of cardio-respiratory structure and function compared with normoxic controls (PO2 >20 kPa). The onset and development of the larval and adult hearts were delayed in chronological time in hypoxia, but both organs appeared earlier in developmental time and cardiac activity rates were greater. The velum, a transient, 'larval' organ thought to play a role in gas exchange, was larger in hypoxia but developed more slowly (in chronological time), and velar cilia-driven, rotational activity was lower. Despite these effects of hypoxia, 38% of individuals survived to hatching. Compared with those embryos that died during development, these surviving embryos had advanced expression of adult structures, i.e. a significantly earlier occurrence and greater activity of their adult heart and larger shells. In contrast, embryos that died retained larval cardio-respiratory features (the velum and larval heart) for longer in chronological time. Surviving embryos came from eggs with significantly higher albumen provisioning than those that died, suggesting an energetic component for advanced development of adult traits. © 2016. Published by The Company of Biologists Ltd.
Waziri, Farhad; Lyager Nielsen, Sten; Michael Hasenkam, John
2016-09-01
Tricuspid regurgitation may be a precursor for heart failure, reduced functional capacity, and poor survival. A human compatible experimental model is required to understand the pathophysiology of the tricuspid valve disease as a basis for validating novel tricuspid valve interventions before clinical use. The study aim was to evaluate and compare the tricuspid valve anatomy of porcine and human hearts. The anatomy of the tricuspid valve and the surrounding structures that affect the valve during a cardiac cycle were examined in detail in 100 fresh and 19 formalin-fixed porcine hearts obtained from Danish Landrace pigs (body weight 80 kg). All valvular dimensions were compared with human data acquired from literature sources. No difference was seen in the tricuspid annulus circumference between porcine and human hearts (13.0 ± 1.2 cm versus 13.5 ± 1.5 cm; p = NS), or in valve area (5.7 ± 1.6 cm2 versus 5.6 ± 1.0 cm2; p = NS). The majority of chordae types exhibited a larger chordal length and thickness in human hearts compared to porcine hearts. In both species, the anterior papillary muscle (PM) was larger than other PMs in the right ventricle, but muscle length varied greatly (range: 5.2-40.3 mm) and was significantly different in pigs and in humans (12.2 ± 3.2 mm versus 19.2 mm; p <0.001). The porcine tricuspid valve was determined to be a valid model for preclinical animal studies, despite various anatomic differences being noted between porcine and human hearts.
Anesthetic management of the neonate with congenital complete heart block: a 16-year review.
Kussman, Barry D; Madril, Danielle R; Thiagarajan, Ravi R; Walsh, Edward P; Laussen, Peter C
2005-12-01
Anesthesia for patients with complete heart block can be associated with significant hemodynamic instability. The aim of this study is to review our anesthetic experience of neonates with congenital complete heart block (CCHB) who underwent placement of either a temporary epicardial pacing system or a permanent epicardial pacemaker. The anesthetic management of neonates with CCHB who underwent pacemaker placement at a single institution over a 16-year period was reviewed. Twenty-four neonates were identified, 17 with a structurally normal heart (NL) and seven with associated congenital heart defects (CHD). Median (range) gestational age was 36.9 (26-41) weeks, birth weight 2.9 (1.0-4.1) kg, and baseline heart rate 47 (38-80) b.min(-1). A temporary epicardial pacing system was placed in six patients (four CHD, two NL; P = 0.003) following institution of mechanical ventilation and inotropic support for a low cardiac output state, and a permanent epicardial pacemaker was placed in 18 patients. Atropine 0.02 mg.kg(-1) IV prior to induction (n = 5) increased heart rate less than 20%. Intraoperative hypotension was documented in nine neonates, five of seven with CHD and four of 17 with NL (P = 0.02). In four patients (44%) hypotension occurred despite concurrent inotropic support. Intraoperative cardiac arrest occurred in one neonate, necessitating institution of extracorporeal membrane oxygenation. Two patients (8.3%) died in hospital from complex CHD and complications of prematurity. Early institution of mechanical ventilation, inotropic support and pacing are necessary in the neonate with CCHB and poor hemodynamic function, particularly with coexisting CHD or prematurity.
Yanni, Joseph; Maczewski, Michal; Mackiewicz, Urszula; Siew, Samuel; Fedorenko, Olga; Atkinson, Andrew; Price, Marcus; Beresewicz, Andrzej; Anderson, Robert H; Boyett, Mark R; Dobrzynski, Halina
2014-07-01
Heart failure (HF) causes dysfunction of the atrioventricular node (AVN) - first or second-degree heart block is a risk factor for sudden cardiac death in HF patients. The aim of the study was to determine if HF causes remodelling of the AVN and right atrioventricular ring (RAVR). HF was induced in rats (n=4) by ligation of the proximal left coronary artery, which resulted in a large infarct of the left ventricle. Sham-operated rats (n=4) were used as controls. Eight weeks after surgery, functional experiments were performed and the hearts were frozen. The body weight of HF rats was similar to control rats, but the mean heart weight of HF rats was significantly enlarged. In HF rats compared to controls, the left ventricle was dilated, left ventricular end-diastolic pressure elevated (21.0 ± 0.6 and 5.4 ± 0.2 mm Hg), left ventricular ejection fraction reduced (0.2 ± 0.02 and 0.5 ± 0.02) and left ventricular end-systolic pressure reduced (102 ± 4.2 and 127 ± 3.1 mm Hg). In HF rats, the in vivo and in vitro PR intervals were increased (41% and 20%), as was the Wenckebach cycle length, indicative of AVN dysfunction. The collagen content was significantly increased in the AVN and RAVR indicating fibrosis. Immunolabelling of caveolin3 (cell membrane marker) showed that there was hypertrophy in HF (cell diameter was increased by 63%, 39% in AVN, RAVR). The TUNEL assay showed that the myocytes of the AVN and RAVR in HF undergo apoptotic cell death. Immunolabelling showed that expression of HCN4 was significantly decreased in the AVN and RAVR (43% and 47%) in HF. We conclude that in HF there is remodelling of the AVN and RAVR and this remodelling may explain the AVN dysfunction.
Intracardiac Echocardiography for Structural Heart and Electrophysiological Interventions.
Basman, Craig; Parmar, Yuvrajsinh J; Kronzon, Itzhak
2017-09-06
With an increasing number of interventional procedures performed for structural heart disease and cardiac arrhythmias each year, echocardiographic guidance is necessary for safe and efficient results. The purpose of this review article is to overview the principles of intracardiac echocardiography (ICE) and describes the peri-interventional role of ICE in a variety of structural heart disease and electrophysiological interventions. Both transthoracic (TTE) and transesophageal echocardiography have limitations. ICE provides the advantage of imaging from within the heart, providing shorter image distances and higher resolution. ICE may be performed without sedation and avoids esophageal intubation as with transesophageal echocardiography (TEE). Limitations of ICE include the need for additional venous access with possibility of vascular complications, potentially higher costs, and a learning curve for new operators. Data supports the use of ICE in guiding device closure of interatrial shunts, transseptal puncture, and electrophysiologic procedures. This paper reviews the more recent reports that ICE may be used for primary guidance or as a supplement to TEE in patients undergoing left atrial appendage (LAA) closure, interatrial shunt closure, transaortic valve implantation (TAVI), percutaneous mitral valve repair (PMVR), paravalvular leak (PVL) closure, aortic interventions, transcatheter pulmonary valve replacement (tPVR), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) closure. ICE imaging technology will continue to expand and help improve structural heart and electrophysiology interventions.
Shah, Amil M; Cheng, Susan; Skali, Hicham; Wu, Justina; Mangion, Judy R; Kitzman, Dalane; Matsushita, Kunihiro; Konety, Suma; Butler, Kenneth R; Fox, Ervin R; Cook, Nakela; Ni, Hanyu; Coresh, Josef; Mosley, Thomas H; Heiss, Gerardo; Folsom, Aaron R; Solomon, Scott D
2014-01-01
Heart failure is an important public health concern, particularly among persons>65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community. The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute-sponsored epidemiological cohort study. Between 2011 and 2013, ≈6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure. We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.
Lin, Xue; Yang, Penghua; Reece, E Albert; Yang, Peixin
2017-08-01
Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus. Experimental evidence has implied that pregnant women with type 2 diabetes mellitus and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study revealed that maternal type 2 diabetes mellitus induces structural heart defects in their offspring. This study aims to determine whether maternal type 2 diabetes mellitus induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. The type 2 diabetes mellitus embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, desmin, and adrenomedullin. Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor, osteopontin, and galectin-3 genes. Cell apoptosis also was measured in the developing heart. The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic group. Maternal diabetes significantly increased β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and desmin expression, but decreased expression of adrenomedullin. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type 2 diabetes mellitus activated the proapoptotic c-Jun-N-terminal kinase 1/2 stress signaling and triggered cell apoptosis by increasing the number of terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling-positive cells (10.4 ± 2.2% of the type 2 diabetes mellitus group vs 3.8 ± 0.7% of the nondiabetic group, P < .05). Maternal type 2 diabetes mellitus induces cardiac hypertrophy in embryonic hearts. Adverse cardiac remodeling, including elevated collagen synthesis, suppressed fibronectin synthesis, profibrosis, and apoptosis, is implicated as the etiology of cardiac hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.
Crossman, David J; Young, Alistair A; Ruygrok, Peter N; Nason, Guy P; Baddelely, David; Soeller, Christian; Cannell, Mark B
2015-07-01
Evidence from animal models suggest that t-tubule changes may play an important role in the contractile deficit associated with heart failure. However samples are usually taken at random with no regard as to regional variability present in failing hearts which leads to uncertainty in the relationship between contractile performance and possible t-tubule derangement. Regional contraction in human hearts was measured by tagged cine MRI and model fitting. At transplant, failing hearts were biopsy sampled in identified regions and immunocytochemistry was used to label t-tubules and sarcomeric z-lines. Computer image analysis was used to assess 5 different unbiased measures of t-tubule structure/organization. In regions of failing hearts that showed good contractile performance, t-tubule organization was similar to that seen in normal hearts, with worsening structure correlating with the loss of regional contractile performance. Statistical analysis showed that t-tubule direction was most highly correlated with local contractile performance, followed by the amplitude of the sarcomeric peak in the Fourier transform of the t-tubule image. Other area based measures were less well correlated. We conclude that regional contractile performance in failing human hearts is strongly correlated with the local t-tubule organization. Cluster tree analysis with a functional definition of failing contraction strength allowed a pathological definition of 't-tubule disease'. The regional variability in contractile performance and cellular structure is a confounding issue for analysis of samples taken from failing human hearts, although this may be overcome with regional analysis by using tagged cMRI and biopsy mapping. Copyright © 2015 Elsevier Ltd. All rights reserved.
TTK Chitra tilting disc heart valve model TC2: An assessment of fatigue life and durability.
Subhash, N N; Rajeev, Adathala; Sujesh, Sreedharan; Muraleedharan, C V
2017-08-01
Average age group of heart valve replacement in India and most of the Third World countries is below 30 years. Hence, the valve for such patients need to be designed to have a service life of 50 years or more which corresponds to 2000 million cycles of operation. The purpose of this study was to assess the structural performance of the TTK Chitra tilting disc heart valve model TC2 and thereby address its durability. The TC2 model tilting disc heart valves were assessed to evaluate the risks connected with potential structural failure modes. To be more specific, the studies covered the finite element analysis-based fatigue life prediction and accelerated durability testing of the tilting disc heart valves for nine different valve sizes. First, finite element analysis-based fatigue life prediction showed that all nine valve sizes were in the infinite life region. Second, accelerated durability test showed that all nine valve sizes remained functional for 400 million cycles under experimental conditions. The study ensures the continued function of TC2 model tilting disc heart valves over duration in excess of 50 years. The results imply that the TC2 model valve designs are structurally safe, reliable and durable.
Adachi, M
1995-02-01
Portable 24-hour polygraphic monitorings were performed on 109 cases with neurological or cardiovascular disorders, sleep disturbances and metabolic diseases to clarify its usefulness and limitations. Moreover, an evaluation of autonomic nervous activity was done in different stages of sleep in normal young (n = 9), normal middle-aged subjects (n = 8) and patients with ischemic heart disease (n = 7) using power spectral analysis of heart rate. The parameters recorded in this study were electroencepharogram(EEG), electrooculogram, electromyogram of chin muscles, electrocardiogram, respiratory curve, walking pulse and body position. Using polygraphic monitoring, the patients with cardiac arrhythmia showed abnormal EEG in 20% and those with neurological events in 86.7%. The improvement of sleep structure was found after pacemaker implantation in the patients with bradyarrhythmias (75%). Time spans of slow wave sleep and REM sleep of patients with ischemic heart disease decreased significantly from 120.9 +/- 40.6 min to 79.1 +/- 25.3 min, 112.8 +/- 16.5 min to 63.6 +/- 23.6 min, respectively (p < 0.05). RR50, that is number of R -R intervals greater than 50msec compared to the preceding R-R interval, decreased significantly in each stage of sleep in the patients with ischemic heart disease compared to normal subjects (stage 2: 18.3 +/- 6.1/min to 3.8 +/- 3.0/min, p < 0.01; SWS: 7.8 +/- 8.0/min to 3.2 +/- 2.5/min, p < 0.05; REM: 17.9 +/- 6.0/min to 4.4 +/- 4.3/min, p < 0.01). The HF power in all stages of sleep showed a trend of the decrease in the patients with ischemic heart disease. In REM sleep, the LF power in patients with ischemic disease was lower significantly compared to that in normal middle-aged subjects (6.1 +/- 3.2 to 12.1 +/- 4.1, p < 0.05). The L/H ratio also decreased significantly (1.08 +/- 0.30 vs. 2.35 +/- 1.03, p < 0.05). The slope of 1/fx above 0.15Hz in IHD patients was less in stage 2 (-0.404 +/- 0.280 vs. -0.849 +/- 0.183, p < 0.01) and in REM sleep (-0.294 +/- 0.368 vs. -0.665 +/- 0.291, p < 0.05). Above results suggest the involvement of a decrease of sympathetic activity in addition to decrease of parasympathetic activity especially in REM sleep in the patients with ischemic heart disease. In conclusion, polygraphic monitoring is useful for a detection of abnormality of EEG and an evaluation of autonomic activity in cardiovascular disorders.
Heavy metals in laughing gulls: Gender, age and tissue differences
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gochfeld, M.; Belant, J.L.; Shukla, T.
1996-12-01
The authors examined concentrations of lead, cadmium, mercury, manganese, selenium, and chromium in feathers, liver, kidney, heart, and muscle of known-aged laughing gulls (Larus atricilla) that hatched in Barnegat Bay, New Jersey and were collected at John F. Kennedy International Airport, New York 1 to 7 years later. Concentrations differed significantly among tissues, and tissue entered all the regression models explaining the greatest variation in metal levels. Age of bird contributed significantly to the models for lead, cadmium, selenium, and chromium. Although there were significant gender differences in all body measurements except wing length, there were few differences in metalmore » levels. Males had significantly higher lead levels in feathers, and females had significantly higher selenium levels in heart and muscle tissue. For lead, 3-year olds had the highest levels in the heart, liver, and kidney, and levels were lower thereafter. Mercury levels in feathers and heart decreased significantly with age. Cadmium levels increased significantly with age for feathers, heart, liver, and muscle, although there was a slight decrease in the 7-year olds. Selenium levels decreased significantly with age for all tissues. Chromium levels increased with age for liver and heart.« less
Warszawski, Leila; Kasuki, Leandro; Sá, Rodrigo; Dos Santos Silva, Cintia Marques; Volschan, Isabela; Gottlieb, Ilan; Pedrosa, Roberto Coury; Gadelha, Mônica R
2016-12-01
The incidence of arrhythmias may be increased in acromegaly, but the pathophysiologic mechanisms involved are still unclear, and it has never been correlated with structural heart changes analyzed by the gold-standard method cardiac magnetic resonance (CMR). Evaluate the frequency of arrhythmias in drug-naïve acromegaly patients at baseline and after 1 year of somatostatin analogs (SA) treatment and to correlate the occurrence of arrhythmias with the presence of structural heart changes. Consecutive drug-naïve acromegaly patients were recruited. The occurrence of arrhythmias and structural heart changes were studied through 24-h Holter and CMR, respectively, at baseline and after 1-year SA treatment. Thirty-six patients were studied at baseline and 28 were re-evaluated after 1 year of SA treatment. There were 13 females and median age was 48 years (20-73 years). Nine patients (32 %) were controlled after treatment. No sustained arrhythmias were reported in the 24-h Holter. No arrhythmia-related symptoms were observed. Only two patients presented left ventricular hypertrophy and three patients presented fibrosis at baseline. There was no correlation of the left ventricular mass with the number of episodes of arrhythmias and they were not more prevalent in the patients presenting cardiac fibrosis. We found no sustained arrhythmias and a lack of arrhythmia-related symptoms at baseline and after 1 year of SA treatment in a contemporary cohort of acromegaly patients that also present a low frequency of structural heart changes, indicating that these patients may have a lower frequency of heart disease than previously reported.
The Congenital Heart Surgeons Society Datacenter: unique attributes as a research organization.
Caldarone, Christopher A; Williams, William G
2010-01-01
Over the last 25 years, the Congenital Heart Surgeons Society (CHSS) has evolved from an informal club to a mature organization. A central feature of the CHSS has been dedication to evaluating outcomes of congenital heart surgery across a wide array of clinical diagnoses. These research activities have been orchestrated through the CHSS Datacenter, which has developed a unique organizational structure that has strengths and weaknesses in comparison to other research organizational structures (e.g., prospective randomized trials, registries, etc). This review will highlight the unique attributes of the CHSS Datacenter with emphasis on the Datacenter's strengths and weaknesses in comparison to other organizational structures. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Sharma, Vijay
2009-09-10
Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts.
Sharma, Vijay
2009-01-01
Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts. PMID:19812706
Seebacher, F; Franklin, C E
2001-12-01
During thermoregulation in the bearded dragon Pogona barbata, heart rate when heating is significantly faster than when cooling at any given body temperature (heart rate hysteresis), resulting in faster rates of heating than cooling. However, the mechanisms that control heart rate during heating and cooling are unknown. The aim of this study was to test the hypothesis that changes in cholinergic and adrenergic tone on the heart are responsible for the heart rate hysteresis during heating and cooling in P. barbata. Heating and cooling trials were conducted before and after the administration of atropine, a muscarinic antagonist, and sotalol, a beta-adrenergic antagonist. Cholinergic and beta-adrenergic blockade did not abolish the heart rate hysteresis, as the heart rate during heating was significantly faster than during cooling in all cases. Adrenergic tone was extremely high (92.3 %) at the commencement of heating, and decreased to 30.7 % at the end of the cooling period. Moreover, in four lizards there was an instantaneous drop in heart rate (up to 15 beats min(-1)) as the heat source was switched off, and this drop in heart rate coincided with either a drop in beta-adrenergic tone or an increase in cholinergic tone. Rates of heating were significantly faster during the cholinergic blockade, and least with a combined cholinergic and beta-adrenergic blockade. The results showed that cholinergic and beta-adrenergic systems are not the only control mechanisms acting on the heart during heating and cooling, but they do have a significant effect on heart rate and on rates of heating and cooling.
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.
Goto, Seiko; Park, Bum-Jin; Tsunetsugu, Yuko; Herrup, Karl; Miyazaki, Yoshifumi
2013-01-01
The objective of this study is to trace short-term changes in mood and heart function in elderly individuals in response to exposure to different landscaped spaces. Nineteen elderly but cognitively intact residents of an assisted living facility participated in the study. They were exposed to three landscaped spaces: a Japanese style garden, an herb garden, and a simple landscaped area planted with a single tree. To assess the effect of different landscaped spaces on older adults, individuals were monitored for mood and cardiac function in response to short exposures to spaces. Mood state was assessed using Profile of Mood States (POMS) before and after viewing the spaces. Cardiac output was assessed using a portable electrocardiograph monitor before and during the viewing. We found that the structured gardens evoked greater responses in all outcome measures. Scores on the POMS improved after observation of the two organized gardens compared to responses to the simple landscaped space with a single tree. During the observation period, heart rate was significantly lower in the Japanese garden than in the other environments, and sympathetic function was significantly lower as well. We conclude that exposure to organized gardens can affect both the mood and cardiac physiology of elderly individuals. Our data further suggest that these effects can differ depending on the types of landscape to which an individual is exposed. Elderly, Japanese garden, herb garden, heart rate, mood, healing environmentPreferred Citation: Goto, S., Park, B-J., Tsunetsugu, Y., Herrup, K., & Miyazaki, Y. (2013). The effect of garden designs on mood and heart output in older adults residing in an assisted living facility. Health Environments Research & Design Journal 6(2), pp 27-42.
The Brain in Congenital Heart Disease across the Lifespan: The Cumulative Burden of Injury
Marelli, Ariane; Miller, Steven P.; Marino, Bradley Scott; Jefferson, Angela L.; Newburger, Jane W.
2017-01-01
The number of patients surviving with congenital heart disease (CHD) has soared over the last three decades. Adults constitute the fastest growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has largely been focused on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. In summary, against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions. PMID:27185022
2009-01-01
Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays) representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration) in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level. PMID:20003209
Kiuchi, Márcio Galindo; E Silva, Gustavo Ramalho; Paz, Luis Marcelo Rodrigues; Chen, Shaojie; Souto, Gladyston Luiz Lima
2016-11-01
Polymorphic premature ventricular complexes (PVCs) are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Recently, the relevance of sympathetic activation in patients with ventricular arrhythmias was reported, and this finding suggested a potential role for catheter-based renal sympathetic denervation in reducing the arrhythmic burden. We evaluated the effectiveness of the renal sympathetic denervation (RSD) in comparison to antiarrhythmic pharmacologic therapy in reducing polymorphic PVCs refractory to medication therapy and cardiac parameters assessed by 24-h Holter monitoring and cardiac magnetic resonance (CRM), respectively, in patients with structurally normal heart. Thirty-four patients were included in this study, 14 served as control, and 20 were treated with an ablation cardiac catheter with open irrigated tip. RSD was performed by a single operator following the standard technique. All the patients included had polymorphic PVCs and structurally normal heart. Data were obtained at baseline at the 12th month of follow-up (sixth month after RSD or adjustment of antiarrhythmic dosage). In RSD group, we observed a significant decrease in the number of polymorphic PVCs from baseline 36,091 ± 3327 to 3, 6, 7 (first month after RSD, without drugs), and 12 months (sixth month after RSD, without drugs) of follow-up, 31,009 ± 3251, 20,411 ± 3820, 7701 ± 1549, and 1274 ± 749, respectively, in all patients, P < 0.0001 to all the comparisons between the mean of each time point with the mean of every other time point. No changes in mean 24-h ABPM and renal function in both groups were observed at 12th month of follow-up. However, 24-h Holter mean heart rate decreased in control group at 12th month of follow-up, which did not happen with the RSD group. At the sixth month post-RSD in comparison to baseline, a significant reduction in the number of polymorphic PVCs (∆ = -34,817 ± 3590, P < 0.0001) was observed, as well as, in CRM parameters such as left ventricular mass/body surface area (∆ = -5.4 ± 2.1 g/m 2 , P < 0.0001) and left ventricular ejection fraction (∆ = +3.0 ± 1.8 %, P < 0.0001). In comparison to control group at the same time point, these findings were statistically superior in RSD group (P > 0.05). A significant correlation was found between the Δ number of polymorphic PVCs at the sixth month (r = -0.6723, P = 0.0012) after the RSD and the total number of RSD ablated spots. Polymorphic PVCs refractory to medication therapy may be modifiable by RSD in patients without structural heart disease. Although encouraging, our data are preliminary and need to be validated in a large population and in long term.
Causes of sudden death in young female military recruits.
Eckart, Robert E; Scoville, Stephanie L; Shry, Eric A; Potter, Robert N; Tedrow, Usha
2006-06-15
This study sought to examine the incidence of sudden death in a large, multiethnic cohort of young women. Approximately 852,300 women entered basic military training from 1977 to 2001. During this period, there were 15 sudden deaths in female recruits (median age 19 years, 73% African-American), occurring at a median of 25 days after arrival for training. Of the sudden deaths, 13 (81%) were due to reasons that may have been cardiac in origin. Presumed arrhythmic sudden death in the setting of a structurally normal heart was seen in 8 recruits (53%), and anomalous coronary origins were found in 2 recruits (13%). The mortality rate was 11.4 deaths per 100,000 recruit-years (95% confidence interval 6.9 to 18.9). The rate was significantly higher for African-American female recruits (risk ratio 10.2, p <0.001). Sudden death with a structurally normal heart was the leading cause of death in female recruits during military training.
Reorganization of the brain and heart rhythm during autogenic meditation
Kim, Dae-Keun; Rhee, Jyoo-Hi; Kang, Seung Wan
2014-01-01
The underlying changes in heart coherence that are associated with reported EEG changes in response to meditation have been explored. We measured EEG and heart rate variability (HRV) before and during autogenic meditation. Fourteen subjects participated in the study. Heart coherence scores were significantly increased during meditation compared to the baseline. We found near significant decrease in high beta absolute power, increase in alpha relative power and significant increases in lower (alpha) and higher (above beta) band coherence during 3~min epochs of heart coherent meditation compared to 3~min epochs of heart non-coherence at baseline. The coherence and relative power increase in alpha band and absolute power decrease in high beta band could reflect relaxation state during the heart coherent meditation. The coherence increase in the higher (above beta) band could reflect cortico-cortical local integration and thereby affect cognitive reorganization, simultaneously with relaxation. Further research is still needed for a confirmation of heart coherence as a simple window for the meditative state. PMID:24454283
Reorganization of the brain and heart rhythm during autogenic meditation.
Kim, Dae-Keun; Rhee, Jyoo-Hi; Kang, Seung Wan
2014-01-13
The underlying changes in heart coherence that are associated with reported EEG changes in response to meditation have been explored. We measured EEG and heart rate variability (HRV) before and during autogenic meditation. Fourteen subjects participated in the study. Heart coherence scores were significantly increased during meditation compared to the baseline. We found near significant decrease in high beta absolute power, increase in alpha relative power and significant increases in lower (alpha) and higher (above beta) band coherence during 3~min epochs of heart coherent meditation compared to 3~min epochs of heart non-coherence at baseline. The coherence and relative power increase in alpha band and absolute power decrease in high beta band could reflect relaxation state during the heart coherent meditation. The coherence increase in the higher (above beta) band could reflect cortico-cortical local integration and thereby affect cognitive reorganization, simultaneously with relaxation. Further research is still needed for a confirmation of heart coherence as a simple window for the meditative state.
Zhang, Chengmin; Ohira, Masahiro; Iizuka, Takuo; Mikamo, Hiroshi; Nakagami, Takahiro; Suzuki, Masayo; Hirano, Keiichi; Takahashi, Mao; Shimizu, Kazuhiro; Sugiyama, Yuko; Yamaguchi, Takashi; Kawana, Hidetoshi; Endo, Kei; Saiki, Atsuhito; Oyama, Tomokazu; Kurosu, Takumi; Tomaru, Takanobu; Wang, Hongyu; Noike, Hirofumi; Shirai, Kohji
2013-01-01
The cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive marker of arterial stiffness independent of blood pressure. Arterial stiffness is closely related to afterload, and elevated afterload aggravates heart failure. We hypothesized that CAVI is a potential marker of afterload in patients with heart failure. Thirty patients who were admitted because of acute heart failure were identified retrospectively from a review of clinical records. Plasma brain natriuretic peptide (BNP) levels, CAVI, cardiothoracic ratio (CTR), and echocardiographic parameters obtained during acute and chronic phases of heart failure were analyzed. Left ventricular ejection fraction (LVEF) increased significantly and CTR, BNP and CAVI decreased significantly after treatment of heart failure. A significant negative correlation was observed between the change in CAVI and change in LVEF in all subjects (r = -0.3272, P < 0.05). To examine the relationship between CAVI and LVEF, we divided the patients into two subgroups (∆CAVI < -0.5; CAVI decrease group, ∆CAVI ≥ -0.5; CAVI non-decrease group). CAVI was significantly improved after heart failure treatment only in the CAVI decrease group. LVEF decreased significantly in both groups, but the P value was smaller in the CAVI decrease group than in the CAVI non-decrease group. The change in LVEF correlated significantly with the change in CAVI in the CAVI decrease group (r = -0.4201, P < 0.05), whereas no significant correlation was found in the CAVI non-decrease group. CAVI correlates inversely with LVEF after heart failure treatment. Our results suggest that CAVI might partially reflect the afterload in patients with heart failure.
DeWitt, Jamie C; Millsap, Deborah S; Yeager, Ronnie L; Heise, Steve S; Sparks, Daniel W; Henshel, Diane S
2006-02-01
Necropsy-observable cardiac deformities were evaluated from 283 nestling passerines collected from one reference site and five polychlorinated biphenyl (PCB)-contaminated sites around Bloomington and Bedford, Indiana, USA. Hearts were weighed and assessed on relative scales in three dimensions (height, length, and width) and for externally visible deformities. Heart weights normalized to body weight (heart somatic index) were decreased significantly at the more contaminated sites in both house wren (Troglodytes aedon) and tree swallow (Tachycineta bicolor). Heart somatic indices significantly correlated with log PCB concentrations in Carolina chickadee (Parus carolinesis) and tree swallow and with log 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent values in tree swallow alone. Ventricular length was increased significantly in eastern bluebirds (Sialia sialis) and decreased significantly in Carolina chickadee and tree swallow from contaminated sites versus the reference site. Heart length regressed significantly against the log PCB concentrations (Carolina chickadee and tree swallow) or the square of the PCB concentrations (red-winged blackbird [Agelaius phoeniceus]) in a sibling bird. The deformities that were observed most at the contaminated sites included abnormal tips (pointed, rounded, or flattened), center rolls, macro- and microsurface roughness, ventricular indentations on the ventral or dorsal surface, lateral ventricular notches, visibly thin ventricular walls, and changes in overall heart shape. A pooled heart deformity index regressed significantly against the logged contaminant concentrations for all species except red-winged blackbird. These results indicate that developmental changes in heart morphometrics and shape abnormalities are quantifiable and may be sensitive and useful indicators of PCB-related developmental impacts across many avian species.
Stratification of the Risk of Sudden Death in Nonischemic Heart Failure
Pimentel, Maurício; Zimerman, Leandro Ioschpe; Rohde, Luis Eduardo
2014-01-01
Despite significant therapeutic advancements, heart failure remains a highly prevalent clinical condition associated with significant morbidity and mortality. In 30%-40% patients, the etiology of heart failure is nonischemic. The implantable cardioverter-defibrillator (ICD) is capable of preventing sudden death and decreasing total mortality in patients with nonischemic heart failure. However, a significant number of patients receiving ICD do not receive any kind of therapy during follow-up. Moreover, considering the situation in Brazil and several other countries, ICD cannot be implanted in all patients with nonischemic heart failure. Therefore, there is an urgent need to identify patients at an increased risk of sudden death because these would benefit more than patients at a lower risk, despite the presence of heart failure in both risk groups. In this study, the authors review the primary available methods for the stratification of the risk of sudden death in patients with nonischemic heart failure. PMID:25352509
Psychosocial work environment and coronary heart disease.
Danelia, M; Trapaidze, D
2005-04-01
In Georgia, like the other post Soviet republics, CHD morbidity is increasing, especially among young and middle aged people-- i.e. among those who should have the most working ability-- that points at both individual and social significance of the problem. CHD is becoming more and more common among rural inhabitants, different professional groups involved not only in mental but also in physical work. The longstanding observation that rates of coronary heart disease vary markedly among occupations more than can be accounted for by conventional risk factors for coronary heart disease has generated a quest for specific components of work that might be of etiological importance. Especially when according to structural changes in society the role of social and psychological factors increased. Case-control study was carried out based on Karasek model. Our results indicate that jobs characterized by low decision latitude, high job strain and low social support at work may be associated with an increased risk of acute coronary events.
Nanotechnology-Based Cardiac Targeting and Direct Cardiac Reprogramming: The Betrothed.
Passaro, Fabiana; Testa, Gianluca; Ambrosone, Luigi; Costagliola, Ciro; Tocchetti, Carlo Gabriele; di Nezza, Francesca; Russo, Michele; Pirozzi, Flora; Abete, Pasquale; Russo, Tommaso; Bonaduce, Domenico
2017-01-01
Cardiovascular diseases represent the first cause of morbidity in Western countries, and chronic heart failure features a significant health care burden in developed countries. Efforts in the attempt of finding new possible strategies for the treatment of CHF yielded several approaches based on the use of stem cells. The discovery of direct cardiac reprogramming has unveiled a new approach to heart regeneration, allowing, at least in principle, the conversion of one differentiated cell type into another without proceeding through a pluripotent intermediate. First developed for cancer treatment, nanotechnology-based approaches have opened new perspectives in many fields of medical research, including cardiovascular research. Nanotechnology could allow the delivery of molecules with specific biological activity at a sustained and controlled rate in heart tissue, in a cell-specific manner. Potentially, all the mediators and structural molecules involved in the fibrotic process could be selectively targeted by nanocarriers, but to date, only few experiences have been made in cardiac research. This review highlights the most prominent concepts that characterize both the field of cardiac reprogramming and a nanomedicine-based approach to cardiovascular diseases, hypothesizing a possible synergy between these two very promising fields of research in the treatment of heart failure.
Nanotechnology-Based Cardiac Targeting and Direct Cardiac Reprogramming: The Betrothed
Pirozzi, Flora; Abete, Pasquale; Bonaduce, Domenico
2017-01-01
Cardiovascular diseases represent the first cause of morbidity in Western countries, and chronic heart failure features a significant health care burden in developed countries. Efforts in the attempt of finding new possible strategies for the treatment of CHF yielded several approaches based on the use of stem cells. The discovery of direct cardiac reprogramming has unveiled a new approach to heart regeneration, allowing, at least in principle, the conversion of one differentiated cell type into another without proceeding through a pluripotent intermediate. First developed for cancer treatment, nanotechnology-based approaches have opened new perspectives in many fields of medical research, including cardiovascular research. Nanotechnology could allow the delivery of molecules with specific biological activity at a sustained and controlled rate in heart tissue, in a cell-specific manner. Potentially, all the mediators and structural molecules involved in the fibrotic process could be selectively targeted by nanocarriers, but to date, only few experiences have been made in cardiac research. This review highlights the most prominent concepts that characterize both the field of cardiac reprogramming and a nanomedicine-based approach to cardiovascular diseases, hypothesizing a possible synergy between these two very promising fields of research in the treatment of heart failure. PMID:29375623
Folsom, Aaron R.; Shah, Amil M.; Lutsey, Pamela L.; Roetker, Nicholas S.; Alonso, Alvaro; Avery, Christy L.; Miedema, Michael D.; Konety, Suma; Chang, Patricia P.; Solomon, Scott D.
2015-01-01
BACKGROUND Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association’s Life’s Simple 7 guidelines -- on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose -- is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. METHODS We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults aged 45-64 years in 1987-89. From the 1987-89 risk factor measurements, we created a Life’s Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2,218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4,855 participants free of clinical cardiovascular disease in 2011-13, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS One in four participants (25.5%) developed heart failure through age 85. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life’s Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life’s Simple 7 score compared with an inadequate score. CONCLUSIONS Greater achievement of American Heart Association’s Life’s Simple 7 in middle-age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. PMID:25908393
Van Dyke, Miriam E; Komro, Kelli A; Shah, Monica P; Livingston, Melvin D; Kramer, Michael R
2018-07-01
Despite substantial declines since the 1960's, heart disease remains the leading cause of death in the United States (US) and geographic disparities in heart disease mortality have grown. State-level socioeconomic factors might be important contributors to geographic differences in heart disease mortality. This study examined the association between state-level minimum wage increases above the federal minimum wage and heart disease death rates from 1980 to 2015 among 'working age' individuals aged 35-64 years in the US. Annual, inflation-adjusted state and federal minimum wage data were extracted from legal databases and annual state-level heart disease death rates were obtained from CDC Wonder. Although most minimum wage and health studies to date use conventional regression models, we employed marginal structural models to account for possible time-varying confounding. Quasi-experimental, marginal structural models accounting for state, year, and state × year fixed effects estimated the association between increases in the state-level minimum wage above the federal minimum wage and heart disease death rates. In models of 'working age' adults (35-64 years old), a $1 increase in the state-level minimum wage above the federal minimum wage was on average associated with ~6 fewer heart disease deaths per 100,000 (95% CI: -10.4, -1.99), or a state-level heart disease death rate that was 3.5% lower per year. In contrast, for older adults (65+ years old) a $1 increase was on average associated with a 1.1% lower state-level heart disease death rate per year (b = -28.9 per 100,000, 95% CI: -71.1, 13.3). State-level economic policies are important targets for population health research. Copyright © 2018 Elsevier Inc. All rights reserved.
Zangger, Graziella; Zwisler, Ann-Dorthe; Kikkenborg Berg, Selina; Kristensen, Marie S; Grønset, Charlotte N; Uddin, Jamal; Pedersen, Susanne S; Oldridge, Neil B; Thygesen, Lau C
2018-01-01
Background Patient-reported health-related quality of life is increasingly used as an outcome measure in clinical trials and as a performance measure to evaluate quality of care. The objective of this study was to assess the psychometric properties of the Danish HeartQoL questionnaire, a core heart disease-specific health-related quality of life questionnaire, in implantable cardioverter defibrillator recipients. Design This study involved cross-sectional and test-retest study designs. Method Implantable cardioverter defibrillator recipients in the cross-sectional study completed the HeartQoL, the Short-Form 36 Health Survey, and the Hospital Anxiety and Depression Scale. The HeartQoL structure, construct-related validity (convergent and discriminative) and reliability (internal consistency) were assessed. HeartQoL reproducibility (test-retest) was assessed in an independent sample of implantable cardioverter defibrillator recipients. Results Mokken scale analysis supported the bi-dimensional structure of HeartQoL among 358 implantable cardioverter defibrillator recipients. Convergent ( r > 0.72) and discriminative validity were confirmed. The HeartQoL scales demonstrated satisfactory internal consistency (Cronbach's alpha > 0.90). Test-retest reliability (two weeks interval) was assessed in 89 implantable cardioverter defibrillator recipients and found to be acceptable for each scale (intra-class correlation > 0.90). Conclusion The Danish HeartQoL questionnaire demonstrated satisfactory key psychometric attributes of validity and reliability in this implantable cardioverter defibrillator population. This study adds support for the HeartQoL as a core heart-specific health-related quality of life questionnaire in a broad group of patients with heart disease including implantable cardioverter defibrillator recipients.
Remote patient monitoring in chronic heart failure.
Palaniswamy, Chandrasekar; Mishkin, Aaron; Aronow, Wilbert S; Kalra, Ankur; Frishman, William H
2013-01-01
Heart failure (HF) poses a significant economic burden on our health-care resources with very high readmission rates. Remote monitoring has a substantial potential to improve the management and outcome of patients with HF. Readmission for decompensated HF is often preceded by a stage of subclinical hemodynamic decompensation, where therapeutic interventions would prevent subsequent clinical decompensation and hospitalization. Various methods of remote patient monitoring include structured telephone support, advanced telemonitoring technologies, remote monitoring of patients with implanted cardiac devices such as pacemakers and defibrillators, and implantable hemodynamic monitors. Current data examining the efficacy of remote monitoring technologies in improving outcomes have shown inconsistent results. Various medicolegal and financial issues need to be addressed before widespread implementation of this exciting technology can take place.
Fu, Qin; Hu, Yuting; Wang, Qingtong; Liu, Yongming; Li, Ning; Xu, Bing; Kim, Sungjin; Chiamvimonvat, Nipavan; Xiang, Yang K
2017-03-15
Patients with diabetes show a blunted cardiac inotropic response to β-adrenergic stimulation despite normal cardiac contractile reserve. Acute insulin stimulation impairs β-adrenergically induced contractile function in isolated cardiomyocytes and Langendorff-perfused hearts. In this study, we aimed to examine the potential effects of hyperinsulinaemia associated with high-fat diet (HFD) feeding on the cardiac β 2 -adrenergic receptor signalling and the impacts on cardiac contractile function. We showed that 8 weeks of HFD feeding leads to reductions in cardiac functional reserve in response to β-adrenergic stimulation without significant alteration of cardiac structure and function, which is associated with significant changes in β 2 -adrenergic receptor phosphorylation at protein kinase A and G-protein receptor kinase sites in the myocardium. The results suggest that clinical intervention might be applied to subjects in early diabetes without cardiac symptoms to prevent further cardiac complications. Patients with diabetes display reduced exercise capability and impaired cardiac contractile reserve in response to adrenergic stimulation. We have recently uncovered an insulin receptor and adrenergic receptor signal network in the heart. The aim of this study was to understand the impacts of high-fat diet (HFD) on the insulin-adrenergic receptor signal network in hearts. After 8 weeks of HFD feeding, mice exhibited diabetes, with elevated insulin and glucose concentrations associated with body weight gain. Mice fed an HFD had normal cardiac structure and function. However, the HFD-fed mice displayed a significant elevation of phosphorylation of the β 2 -adrenergic receptor (β 2 AR) at both the protein kinase A site serine 261/262 and the G-protein-coupled receptor kinase site serine 355/356 and impaired adrenergic reserve when compared with mice fed on normal chow. Isolated myocytes from HFD-fed mice also displayed a reduced contractile response to adrenergic stimulation when compared with those of control mice fed normal chow. Genetic deletion of the β 2 AR led to a normalized adrenergic response and preserved cardiac contractile reserve in HFD-fed mice. Together, these data indicate that HFD promotes phosphorylation of the β 2 AR, contributing to impairment of cardiac contractile reserve before cardiac structural and functional remodelling, suggesting that early intervention in the insulin-adrenergic signalling network might be effective in prevention of cardiac complications in diabetes. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
Hu, Yuting; Wang, Qingtong; Liu, Yongming; Li, Ning; Xu, Bing; Kim, Sungjin; Chiamvimonvat, Nipavan
2017-01-01
Key points Patients with diabetes show a blunted cardiac inotropic response to β‐adrenergic stimulation despite normal cardiac contractile reserve.Acute insulin stimulation impairs β‐adrenergically induced contractile function in isolated cardiomyocytes and Langendorff‐perfused hearts.In this study, we aimed to examine the potential effects of hyperinsulinaemia associated with high‐fat diet (HFD) feeding on the cardiac β2‐adrenergic receptor signalling and the impacts on cardiac contractile function.We showed that 8 weeks of HFD feeding leads to reductions in cardiac functional reserve in response to β‐adrenergic stimulation without significant alteration of cardiac structure and function, which is associated with significant changes in β2‐adrenergic receptor phosphorylation at protein kinase A and G‐protein receptor kinase sites in the myocardium.The results suggest that clinical intervention might be applied to subjects in early diabetes without cardiac symptoms to prevent further cardiac complications. Abstract Patients with diabetes display reduced exercise capability and impaired cardiac contractile reserve in response to adrenergic stimulation. We have recently uncovered an insulin receptor and adrenergic receptor signal network in the heart. The aim of this study was to understand the impacts of high‐fat diet (HFD) on the insulin–adrenergic receptor signal network in hearts. After 8 weeks of HFD feeding, mice exhibited diabetes, with elevated insulin and glucose concentrations associated with body weight gain. Mice fed an HFD had normal cardiac structure and function. However, the HFD‐fed mice displayed a significant elevation of phosphorylation of the β2‐adrenergic receptor (β2AR) at both the protein kinase A site serine 261/262 and the G‐protein‐coupled receptor kinase site serine 355/356 and impaired adrenergic reserve when compared with mice fed on normal chow. Isolated myocytes from HFD‐fed mice also displayed a reduced contractile response to adrenergic stimulation when compared with those of control mice fed normal chow. Genetic deletion of the β2AR led to a normalized adrenergic response and preserved cardiac contractile reserve in HFD‐fed mice. Together, these data indicate that HFD promotes phosphorylation of the β2AR, contributing to impairment of cardiac contractile reserve before cardiac structural and functional remodelling, suggesting that early intervention in the insulin–adrenergic signalling network might be effective in prevention of cardiac complications in diabetes. PMID:27983752
Altered myofilament structure and function in dogs with Duchenne muscular dystrophy cardiomyopathy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ait Mou, Younss; Lacampagne, Alain; Irving, Thomas
Aim Duchenne Muscular Dystrophy (DMD) is associated with progressive depressed left ventricular (LV) function. However, DMD effects on myofilament structure and function are poorly understood. Golden Retriever Muscular Dystrophy (GRMD) is a dog model of DMD recapitulating the human form of DMD. Objective The objective of this study is to evaluate myofilament structure and function alterations in GRMD model with spontaneous cardiac failure. Methods and results We have employed synchrotron X-rays diffraction to evaluate myofilament lattice spacing at various sarcomere lengths (SL) on permeabilized LV myocardium. We found a negative correlation between SL and lattice spacing in both sub-epicardium (EPI)more » and sub-endocardium (ENDO) LV layers in control dog hearts. In the ENDO of GRMD hearts this correlation is steeper due to higher lattice spacing at short SL (1.9 μm). Furthermore, cross-bridge cycling indexed by the kinetics of tension redevelopment (ktr) was faster in ENDO GRMD myofilaments at short SL. We measured post-translational modifications of key regulatory contractile proteins. S-glutathionylation of cardiac Myosin Binding Protein-C (cMyBP-C) was unchanged and PKA dependent phosphorylation of the cMyBP-C was significantly reduced in GRMD ENDO tissue and more modestly in EPI tissue. Conclusions We found a gradient of contractility in control dogs' myocardium that spreads across the LV wall, negatively correlated with myofilament lattice spacing. Chronic stress induced by dystrophin deficiency leads to heart failure that is tightly associated with regional structural changes indexed by increased myofilament lattice spacing, reduced phosphorylation of regulatory proteins and altered myofilament contractile properties in GRMD dogs.« less
Cell counting in whole mount tissue volumes using expansion OCT (Conference Presentation)
NASA Astrophysics Data System (ADS)
Liu, Yehe; Gu, Shi; Watanabe, Michiko; Rollins, Andrew M.; Jenkins, Michael W.
2017-02-01
Abnormal cell proliferation and migration during heart development can lead to severe congenital heart defects (CHDs). Studying the spatial distribution of cells during embryonic development helps our understanding of how the heart develops and the etiology of certain CHDs. However, imaging large groups of single cells in intact tissue volumes is challenging. No current technique can accomplish this task in both a time-efficient and cost-effective manner. OCT has potential with its large field of view and micron-scale resolution, but even the highest resolution OCT systems have poor contrast for counting cells and have a small field of view compared to conventional OCT. We propose using a conventional OCT system and processing the sample to enhance cellular contrast. Inspired by the recently developed Expansion Microscopy, we permeated whole-mount embryonic tissue with a superabsorbent monomer solution and polymerized into a hydrogel. When hydrated in DI water, the tissue-hydrogel complex was uniformly enlarged ( 5X in all dimensions) without distorting the microscopic structure. This had a twofold effect: it increased the resolution by a factor of 5 and decreased scattering, which allowed us to resolve cellular level features deep in the tissue with high contrast using conventional OCT. We noted that cell nuclei caused significantly more backscattering than the other subcellular structures after expansion. Based on this property, we were able to distinguish individual cell nuclei, and thus count cells, in expanded OCT images with simple intensity thresholding. We demonstrate the technique with embryonic quail hearts at various developmental stages.
EMPOWERING ADULT STEM CELLS FOR MYOCARDIAL REGENERATION
Mohsin, Sadia; Siddiqi, Sailay; Collins, Brett; Sussman, Mark A.
2012-01-01
Treatment strategies for heart failure remain a high priority for ongoing research due to the profound unmet need in clinical disease coupled with lack of significant translational progress. The underlying issue is the same whether the cause is acute damage, chronic stress from disease, or aging: progressive loss of functional cardiomyocytes and diminished hemodynamic output. To stave off cardiomyocyte losses, a number of strategic approaches have been embraced in recent years involving both molecular and cellular approaches to augment myocardial structure and performance. Resultant excitement surrounding regenerative medicine in the heart has been tempered by realizations that reparative processes in the heart are insufficient to restore damaged myocardium to normal functional capacity and that cellular cardiomyoplasty is hampered by poor survival, proliferation, engraftment and differentiation of the donated population. To overcome these limitations, a combination of molecular and cellular approaches needs to be adopted involving use of genetic engineering to enhance resistance to cell death and increase regenerative capacity. This review will highlight biological properties of approached to potentiate stem cell-mediated regeneration to promote enhanced myocardial regeneration, persistence of donated cells, and long lasting tissue repair. Optimizing cell delivery and harnessing the power of survival signaling cascades for ex vivo genetic modification of stem cells prior to reintroduction into the patient will be critical to enhance the efficacy of cellular cardiomyoplasty. Once this goal is achieved, then cell-based therapy has great promise for treatment of heart failure to combat the loss of cardiac structure and function associated with acute damage, chronic disease or aging. PMID:22158649
Palazzuoli, Alberto; Silverberg, Donald S; Calabrò, Anna; Spinelli, Tommaso; Quatrini, Ilaria; Campagna, Maria S; Franci, Beatrice; Nuti, Ranuccio
2009-06-01
Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of beta-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous beta-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with beta-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate.
Blood pressure response is impaired in patients with exercise-induced ventricular ectopy.
Turan, Oguzhan Ekrem; Ozturk, Mustafa; Kocaoglu, Ibrahim; Turan, Selen Gursoy
2016-05-01
Exercise-induced ventricular ectopy (EIVE) has clinical and prognostic significance. But the mechanism underlying EIVE-related mortality still remains unclear. This study aims to assess blood pressure alteration in patients with EIVE and to identify the potential causes of increased mortality in this patient group. A total number of 3611 patients were screened within a 1-year period, and patients with a structural heart disease, coronary artery disease, hypertension, diabetes mellitus, thyroid dysfunction, and chronic renal disease were excluded from the study. A total number of 98 patients with no chronic disease, who were retrospectively diagnosed with EIVE, were included in the study as patient group and 116 patients without EIVE were included as control group. The median age, gender distribution, laboratory test results, and echocardiographic findings were similar between the two groups. Systolic blood pressure (SBP) alterations during exercise stress testing were found to be significantly different (P < .001). Moreover, EIVE group had significantly higher peak SBP (P < .001). A significant positive relation was found between peak SBP level and ventricular ectopy count (r:0.27, P = .006). Our study showed that EIVE patients without a structural heart disease or a chronic disease had higher peak SBP levels. Higher SBP alteration can be related to ventricular ectopy occurrence during exercise stress testing, which can be a possible reason underlying the increased rate of mortality among EIVE patients. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
[Review of wireless energy transmission system for total artificial heart].
Zhang, Chi; Yang, Ming
2009-11-01
This paper sums up the fundamental structure of wireless energy transmission system for total artificial heart, and compares the key parameters and performance of some representative systems. After that, it is discussed that the future development trend of wireless energy transmission system for total artificial heart.
Inspector, Yoram; Kutz, Ilan; David, Daniel
2004-01-01
The goal of this study was to examine heart transplant recipients' psychological adaptation to another person's heart, with particular emphasis on recipients' attitudes toward graft and donor. Thirty-five male heart recipients were examined by: the Symptom Distress Checklist (revised) (SCL-90-R); the Depression Adjective Checklist (DACL); a Post-Traumatic Stress Disorder Questionnaire (PTSD-Q); a Heart Image Questionnaire (HIQ); and a Semi-Structured Interview (SSI), aimed at eliciting attitudes and fantasies regarding the transplanted heart. All instruments indicated high levels of stress even several years after the transplant, but, simultaneously, 73% of recipients felt that acquiring a new heart had had a dramatic influence on their lives with a new appreciation of the preciousness of life and a shift of priorities, toward altruism and spirituality. Sixty percent returned to work after the transplant but some had to adapt to a changed attitude from those around them who regarded them as anything from mystical creatures to vulnerable or still-sick individuals. While all recipients possessed a scientific knowledge of the anatomy and physiological significance of the heart (as revealed in the HIQ), many endorsed fantasies and displayed magical thinking: 46% of the recipients had fantasies about the donor's physical vigor and prowess, 40% expressed some guilt regarding the death of the donor, 34% entertained the possibility of acquiring qualities of the donor via the new heart. When asked to choose a most and least preferred imagined donor, 49% constructed their choices according to prejudices, desires, or fears related to ethnic, racial or sexual traits attributed to the donor. This study confirms the intuitive idea that heart transplant involves a stressful course of events that produces an amplified sense of the precariousness of existence. Simultaneously, it gives rise to rejoicing at having been granted a new lease on life and a clear sense of new priorities, especially with regard to relationships. Less expectedly, this study shows that, despite sophisticated knowledge of anatomy and physiology, almost half the heart recipients had an overt or covert notion of potentially acquiring some of the donor's personality characteristics along with the heart. The concomitance of the magical and the logical is not uncommon in many areas of human existence, and is probably enhanced by the symbolic nature of the heart, and maybe, also, by the persistent stress that requires an ongoing, emotionally intense, adaptation process.
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.
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.
Yokokawa, Miki; Jung, Dae Yon; Joseph, Kim K; Hero, Alfred O; Morady, Fred; Bogun, Frank
2014-11-01
Twelve-lead electrocardiogram (ECG) criteria for epicardial ventricular tachycardia (VT) origins have been described. In patients with structural heart disease, the ability to predict an epicardial origin based on QRS morphology is limited and has been investigated only for limited regions in the heart. The purpose of this study was to determine whether a computerized algorithm is able to accurately differentiate epicardial vs endocardial origins of ventricular arrhythmias. Endocardial and epicardial pace-mapping were performed in 43 patients at 3277 sites. The 12-lead ECGs were digitized and analyzed using a mixture of gaussian model (MoG) to assess whether the algorithm was able to identify an epicardial vs endocardial origin of the paced rhythm. The MoG computerized algorithm was compared to algorithms published in prior reports. The computerized algorithm correctly differentiated epicardial vs endocardial pacing sites for 80% of the sites compared to an accuracy of 42% to 66% of other described criteria. The accuracy was higher in patients without structural heart disease than in those with structural heart disease (94% vs 80%, P = .0004) and for right bundle branch block (82%) compared to left bundle branch block morphologies (79%, P = .001). Validation studies showed the accuracy for VT exit sites to be 84%. A computerized algorithm was able to accurately differentiate the majority of epicardial vs endocardial pace-mapping sites. The algorithm is not region specific and performed best in patients without structural heart disease and with VTs having a right bundle branch block morphology. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Measurement of wall shear stress in chick embryonic heart using optical coherence tomography
NASA Astrophysics Data System (ADS)
Ma, Zhenhe; Dou, Shidan; Zhao, Yuqian; Wang, Yi; Suo, Yanyan; Wang, Fengwen
2015-03-01
The cardiac development is a complicated process affected by genetic and environmental factors. Wall shear stress (WSS) is one of the components which have been proved to influence the morphogenesis during early stages of cardiac development. To study the mechanism, WSS measurement is a step with significant importance. WSS is caused by blood flow imposed on the inner surface of the heart wall and it can be determined by calculating velocity gradients of blood flow in a direction perpendicular to the wall. However, the WSS of the early stage embryonic heart is difficult to measure since the embryonic heart is tiny and beating fast. Optical coherence tomography (OCT) is a non-invasive imaging modality with high spatial and temporal resolution, which is uniquely suitable for the study of early stage embryonic heart development. In this paper, we introduce a method to measure the WSS of early stage chick embryonic heart based on high speed spectral domain optical coherence tomography (SDOCT). 4D (x,y,z,t) scan was performed on the outflow tract (OFT) of HH18 (~3 days of incubation) chick embryonic heart. After phase synchronization, OFT boundary segmentation, and OFT center line calculation, Doppler angle of the blood flow in the OFT can be achieved (This method has been described in previous publications). Combining with the Doppler OCT results, we calculate absolute blood flow velocity distribution in the OFT. The boundary of the OFT was segmented at each cross-sectional structural image, then geometrical center of the OFT can be calculated. Thus, the gradients of blood flow in radial direction can be calculated. This velocity gradient near the wall is termed wall shear rate and the WSS value is proportional to the wall shear rate. Based on this method, the WSS at different heart beating phase are compare. The result demonstrates that OCT is capable of early stage chicken embryonic heart WSS study.
SHI, LIHUA; SONG, JIE; ZHANG, XIAODONG; LI, YING; LI, HUI
2013-01-01
The aim of this study was to examine the correlation between the microinflammatory state and structural and functional changes of the left ventricle in maintenance haemodialysis patients (MHD). In total, 48 MHD patients and 30 healthy volunteers participated in this study. The microinflammatory state was detected from high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels determined by ELISA. The structure and function of the left ventricle was measured according to ultrasound cardiogram examination. The serum levels of hs-CRP, IL-6 and TNF-α in the MHD patients were higher compared with those in the controls (P<0.05). Furthermore, the measurements of the left atrial diameter (LAD), left venticular diameter (LVD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT) and the left ventricular mass index (LVMI) increased significantly and the left ventricular function (LVEF) was reduced. Correlation analysis demonstrated that the concentrations of hs-CRP, TNF-α and IL-6 correlated with the LVMI (P<0.05), but only hs-CRP correlated with the loss of function of the heart in the haemodialysis patients (P<0.05). The microinflammatory state may be closely associated with the structural and functional impairment of the heart in MHD patients. PMID:24137221
Cardiac troponin T is necessary for normal development in the embryonic chick heart.
England, Jennifer; Pang, Kar Lai; Parnall, Matthew; Haig, Maria Isabel; Loughna, Siobhan
2016-09-01
The heart is the first functioning organ to develop during embryogenesis. The formation of the heart is a tightly regulated and complex process, and alterations to its development can result in congenital heart defects. Mutations in sarcomeric proteins, such as alpha myosin heavy chain and cardiac alpha actin, have now been associated with congenital heart defects in humans, often with atrial septal defects. However, cardiac troponin T (cTNT encoded by gene TNNT2) has not. Using gene-specific antisense oligonucleotides, we have investigated the role of cTNT in chick cardiogenesis. TNNT2 is expressed throughout heart development and in the postnatal heart. TNNT2-morpholino treatment resulted in abnormal atrial septal growth and a reduction in the number of trabeculae in the developing primitive ventricular chamber. External analysis revealed the development of diverticula from the ventricular myocardial wall which showed no evidence of fibrosis and still retained a myocardial phenotype. Sarcomeric assembly appeared normal in these treated hearts. In humans, congenital ventricular diverticulum is a rare condition, which has not yet been genetically associated. However, abnormal haemodynamics is known to cause structural defects in the heart. Further, structural defects, including atrial septal defects and congenital diverticula, have previously been associated with conduction anomalies. Therefore, to provide mechanistic insights into the effect that cTNT knockdown has on the developing heart, quantitative PCR was performed to determine the expression of the shear stress responsive gene NOS3 and the conduction gene TBX3. Both genes were differentially expressed compared to controls. Therefore, a reduction in cTNT in the developing heart results in abnormal atrial septal formation and aberrant ventricular morphogenesis. We hypothesize that alterations to the haemodynamics, indicated by differential NOS3 expression, causes these abnormalities in growth in cTNT knockdown hearts. In addition, the muscular diverticula reported here suggest a novel role for mutations of structural sarcomeric proteins in the pathogenesis of congenital cardiac diverticula. From these studies, we suggest TNNT2 is a gene worthy of screening for those with a congenital heart defect, particularly atrial septal defects and ventricular diverticula. © 2016 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.
Diagnosis and management of heart failure in the fetus
DAVEY, B.; SZWAST, A.; RYCHIK, J.
2015-01-01
Heart failure can be defined as the inability of the heart to sufficiently support the circulation. In the fetus, heart failure can be caused by a myriad of factors that include fetal shunting abnormalities, genetic cardiomyopathies, extracardiac malformations, arrhythmias and structural congenital heart disease. With advances in ultrasound has come the ability to characterize many complex conditions, previously poorly understood. Fetal echocardiography provides the tools necessary to evaluate and understand the various physiologies that contribute to heart failure in the fetus. In this review, we will explore the different mechanisms of heart failure in this unique patient population and highlight the role of fetal echocardiography in the current management of these conditions PMID:22992530
Make Your Own Working Models of Heart Valves!
ERIC Educational Resources Information Center
Hudson, Margaret L.
2014-01-01
Heart valves play a vital role in efficient circulation of the blood, and the details of their physical structure are related crucially to their function. However, it can be challenging for the learner to make the mental connection between anatomical structures of valves and the changing pressure gradients that the valves experience and come to an…
The Representation of Heart Development in the Gene Ontology
Khodiyar, Varsha K.; Hill, David P.; Howe, Doug; Berardini, Tanya Z.; Tweedie, Susan; Talmud, Philippa J.; Breckenridge, Ross; Bhattarcharya, Shoumo; Riley, Paul; Scambler, Peter; Lovering, Ruth C.
2012-01-01
An understanding of heart development is critical in any systems biology approach to cardiovascular disease. The interpretation of data generated from high-throughput technologies (such as microarray and proteomics) is also essential to this approach. However, characterizing the role of genes in the processes underlying heart development and cardiovascular disease involves the non-trivial task of data analysis and integration of previous knowledge. The Gene Ontology (GO) Consortium provides structured controlled biological vocabularies that are used to summarize previous functional knowledge for gene products across all species. One aspect of GO describes biological processes, such as development and signaling. In order to support high-throughput cardiovascular research, we have initiated an effort to fully describe heart development in GO; expanding the number of GO terms describing heart development from 12 to over 280. This new ontology describes heart morphogenesis, the differentiation of specific cardiac cell types, and the involvement of signaling pathways in heart development and aligns GO with the current views of the heart development research community and its representation in the literature. This extension of GO allows gene product annotators to comprehensively capture the genetic program leading to the developmental progression of the heart. This will enable users to integrate heart development data across species, resulting in the comprehensive retrieval of information about this subject. The revised GO structure, combined with gene product annotations, should improve the interpretation of data from high-throughput methods in a variety of cardiovascular research areas, including heart development, congenital cardiac disease, and cardiac stem cell research. Additionally, we invite the heart development community to contribute to the expansion of this important dataset for the benefit of future research in this area. PMID:21419760
Orzan, F; Brusca, A; Conte, M R; Presbitero, P; Figliomeni, M C
1993-01-01
OBJECTIVE--To define the clinical and angiographic features and the therapeutic problems in patients with coronary artery disease after therapeutic irradiation of the chest. DESIGN--An observational retrospective study. SETTING--The cardiac catheterisation laboratory, university medical school. PATIENTS--15 subjects (8 men and 7 women, aged 25-56 years, mean 44) examined in the cardiac catheterisation laboratory, who had significant coronary artery disease years after having radiation treatment to the chest and anterior mediastinum. In the early stages of the study angiography was performed because of typical symptoms of ischaemic heart disease. Later on it was performed because of a high index of suspicion in people with signs of extensive radiation heart damage. MAIN OUTCOME MEASURES--Clinical and electrocardiographic evidence of ischaemic heart disease; echocardiographic signs of pericardial, myocardial or valvar involvement; angiographic evidence of coronary arterial stenosis, with special attention to the ostia; haemodynamic and angiographic signs of pericardial, myocardial, and valvar disease. Survival and symptomatic and functional status were ascertained after medical or surgical treatment. RESULTS--The patients were relatively young and had no risk factors. Seven patients had no signs or symptoms of ischaemic heart disease. Ten patients had ostial stenosis, which was associated with extensive involvement of other cardiac structures in nine of them. Seven required surgical treatment for coronary artery disease. Two died, one at surgery and the other one six months later. Five patients had complications associated with irradiation. CONCLUSIONS--Coronary arterial disease can be reasonably ascribed to the effects of chest irradiation when the patients are young and free from risk factors, especially if the obstructions are ostial and there is important damage to other cardiac structures. In patients with damage to other cardiac structures angina and infarction are often absent and coronary angiography seems to be mandatory. Patients often require surgical treatment and postoperative complications are common. PMID:8343315
Heart rate profile during exercise in patients with early repolarization.
Cay, Serkan; Cagirci, Goksel; Atak, Ramazan; Balbay, Yucel; Demir, Ahmet Duran; Aydogdu, Sinan
2010-09-01
Both early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise. A total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed. Both groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrement of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P < 0.05). The lower heart rate increment (< 106 beats/min) and heart rate decrement (< 95 beats/min) were significantly associated with the presence of early repolarization. After adjustment for age and sex, the multiple-adjusted OR of the risk of presence of early repolarization was 2.98 (95%CI 1.21-7.34) (P = 0.018) and 7.73 (95%CI 2.84-21.03) (P < 0.001) for the lower heart rate increment and heart rate decrement compared to higher levels, respectively. Subjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death.
Hamer, Mark; Boutcher, Yati N; Boutcher, Stephen H
2005-12-01
This study examined differentiated rating of perceived exertion (RPE), heart rate, and heart-rate variability during light cycle ergometry exercise at two different pedal rates. 30 healthy men (22.6 +/- 0.9 yr.) were recruited from a student population and completed a continuous 20-min. cycle ergometry exercise protocol, consisting of a 4-min. warm-up (60 rev./min., 30 Watts), followed by four bouts of 4 min. at different combinations of pedal rate (40 or 80 rev./min.) and power output (40 or 80 Watts). The order of the four combinations was counterbalanced across participants. Heart rate was measured using a polar heart-rate monitor, and parasympathetic balance was assessed through time series analysis of heart-rate variability. Measures were compared using a 2 (pedal rate) x 2 (power output) repeated-measures analysis of variance. RPE was significantly greater (p<.05) at 80 versus 40 rev./min. at 40 W. For both power outputs heart rate was significantly increased, and the high frequency component of heart-rate variability was significantly reduced at 80 compared with 40 rev./min. These findings indicate the RPE was greater at higher than at lower pedalling rates for a light absolute power output which contrasts with previous findings based on use of higher power output. Also, pedal rate had a significant effect on heart rate and heart-rate variability at constant power output.
Kaimoto, Satoshi; Hoshino, Atsushi; Ariyoshi, Makoto; Okawa, Yoshifumi; Tateishi, Shuhei; Ono, Kazunori; Uchihashi, Motoki; Fukai, Kuniyoshi; Iwai-Kanai, Eri; Matoba, Satoaki
2017-02-01
Failing heart loses its metabolic flexibility, relying increasingly on glucose as its preferential substrate and decreasing fatty acid oxidation (FAO). Peroxisome proliferator-activated receptor α (PPAR-α) is a key regulator of this substrate shift. However, its role during heart failure is complex and remains unclear. Recent studies reported that heart failure develops in the heart of myosin heavy chain-PPAR-α transgenic mice in a manner similar to that of diabetic cardiomyopathy, whereas cardiac dysfunction is enhanced in PPAR-α knockout mice in response to chronic pressure overload. We created a pressure-overload heart failure model in mice through transverse aortic constriction (TAC) and activated PPAR-α during heart failure using an inducible transgenic model. After 8 wk of TAC, left ventricular (LV) function had decreased with the reduction of PPAR-α expression in wild-type mice. We examined the effect of PPAR-α induction during heart failure using the Tet-Off system. Eight weeks after the TAC operation, LV construction was preserved significantly by PPAR-α induction with an increase in PPAR-α-targeted genes related to fatty acid metabolism. The increase of expression of fibrosis-related genes was significantly attenuated by PPAR-α induction. Metabolic rates measured by isolated heart perfusions showed a reduction in FAO and glucose oxidation in TAC hearts, but the rate of FAO preserved significantly owing to the induction of PPAR-α. Myocardial high-energy phosphates were significantly preserved by PPAR-α induction. These results suggest that PPAR-α activation during pressure-overloaded heart failure improved myocardial function and energetics. Thus activating PPAR-α and modulation of FAO could be a promising therapeutic strategy for heart failure. NEW & NOTEWORTHY The present study demonstrates the role of PPAR-α activation in the early stage of heart failure using an inducible transgenic mouse model. Induction of PPAR-α preserved heart function, and myocardial energetics. Activating PPAR-α and modulation of fatty acid oxidation could be a promising therapeutic strategy for heart failure. Copyright © 2017 the American Physiological Society.
Cell-accurate optical mapping across the entire developing heart.
Weber, Michael; Scherf, Nico; Meyer, Alexander M; Panáková, Daniela; Kohl, Peter; Huisken, Jan
2017-12-29
Organogenesis depends on orchestrated interactions between individual cells and morphogenetically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighboring cells, which is established and fine-tuned during embryonic development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca 2+ -mapping of all cells in the entire electro-mechanically uncoupled heart during the looping stage of live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging, in vivo studies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs.
Cell-accurate optical mapping across the entire developing heart
Meyer, Alexander M; Panáková, Daniela; Kohl, Peter
2017-01-01
Organogenesis depends on orchestrated interactions between individual cells and morphogenetically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighboring cells, which is established and fine-tuned during embryonic development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca2+-mapping of all cells in the entire electro-mechanically uncoupled heart during the looping stage of live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging, in vivo studies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs. PMID:29286002
Mentz, Robert J; Greiner, Melissa A; DeVore, Adam D; Dunlay, Shannon M; Choudhary, Gaurav; Ahmad, Tariq; Khazanie, Prateeti; Randolph, Tiffany C; Griswold, Michael E; Eapen, Zubin J; O'Brien, Emily C; Thomas, Kevin L; Curtis, Lesley H; Hernandez, Adrian F
2015-03-01
QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-14.4) versus 7.1% (95% CI, 6.3-8.0) and 8.2% (95% CI, 6.9-9.7) versus 4.4% (95% CI, 3.7-5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03-1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01-1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities. © 2015 American Heart Association, Inc.
About Peripheral Artery Disease (PAD)
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Image-based models of cardiac structure in health and disease
Vadakkumpadan, Fijoy; Arevalo, Hermenegild; Prassl, Anton J.; Chen, Junjie; Kickinger, Ferdinand; Kohl, Peter; Plank, Gernot; Trayanova, Natalia
2010-01-01
Computational approaches to investigating the electromechanics of healthy and diseased hearts are becoming essential for the comprehensive understanding of cardiac function. In this article, we first present a brief review of existing image-based computational models of cardiac structure. We then provide a detailed explanation of a processing pipeline which we have recently developed for constructing realistic computational models of the heart from high resolution structural and diffusion tensor (DT) magnetic resonance (MR) images acquired ex vivo. The presentation of the pipeline incorporates a review of the methodologies that can be used to reconstruct models of cardiac structure. In this pipeline, the structural image is segmented to reconstruct the ventricles, normal myocardium, and infarct. A finite element mesh is generated from the segmented structural image, and fiber orientations are assigned to the elements based on DTMR data. The methods were applied to construct seven different models of healthy and diseased hearts. These models contain millions of elements, with spatial resolutions in the order of hundreds of microns, providing unprecedented detail in the representation of cardiac structure for simulation studies. PMID:20582162
Zamanian, Zahra; Rostami, Reza; Hasanzadeh, Jafar; Hashemi, Hassan
2013-01-01
This study aimed to investigate the effect of noise exposure on blood pressure and heart rate of steel industry workers. In the present cross-sectional study, 50 workers were selected from a steel company in Fars province, Iran, and exposed to 85, 95, and 105 dB noise levels for 5 minutes. The participants' blood pressure and heart rate were measured using Beurer BC16 pulse meter both before and after the exposure. The study results showed no significant difference in blood pressure and heart rate before and after the exposure. However, the workers' systolic blood pressure had increased compared to before the exposure; of course, the difference was not statistically significant (P > 0.05). Besides, although the subjects' heart rate had reduced in comparison to before the exposure, the difference was not statistically significant (P > 0.05). No significant change was observed in blood pressure and heart rate after acute exposure to 85, 95, and 105 dB noise levels.
Alterations in the heart rate and activity rhythms of three orbital astronauts on a space mission.
Liu, Zhizhen; Wan, Yufeng; Zhang, Lin; Tian, Yu; Lv, Ke; Li, Yinghui; Wang, Chunhui; Chen, Xiaoping; Chen, Shanguang; Guo, Jinhu
2015-01-01
Environmental factors in space are dramatically different from those on Earth. The spaceflight environment has been known to influence human physiology and behavior on orbital missions. In this study, we investigated alterations in the diurnal rhythms of activity and heart rate of three Chinese astronauts on a space mission. An analysis of the heart rate data showed a significant decrease in heart rate amplitudes during flight in all three subjects. The heart rate amplitudes of all the three astronauts were significantly dampened during flight, and the minimum as well as the maximum value of heart rate increased after flight. A phase shift in heart rate was observed in one of the three astronauts after flight. These results demonstrate the influence of spaceflight on heart physiology and function. In addition, a significant decrease in body trunk activity and rhythmicity occurred during flight, demonstrating that the spaceflight environment disturbs motion adaptation and diurnal activity rhythms. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.
Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Noonan, Amanda I.; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko
2014-01-01
Background The most commonly used method to analyze congenital heart defects involves serial sectioning and histology. However, this is often a time-consuming process where the quantification of cardiac defects can be difficult due to problems with accurate section registration. Here we demonstrate the advantages of using optical coherence tomography, a comparatively new and rising technology, to phenotype avian embryo hearts in a model of Fetal Alcohol Syndrome where a binge-like quantity of alcohol/ethanol was introduced at gastrulation. Results The rapid, consistent imaging protocols allowed for the immediate identification of cardiac anomalies, including ventricular septal defects and misaligned/missing vessels. Interventricular septum thicknesses and vessel diameters for three of the five outflow arteries were also significantly reduced. Outflow and atrio-ventricular valves were segmented using image processing software and had significantly reduced volumes compared to controls. This is the first study to our knowledge that has 3-D reconstructed the late-stage cardiac valves in precise detail in order to examine their morphology and dimensions. Conclusion We believe therefore that OCT, with its ability to rapidly image and quantify tiny embryonic structures in high resolution, will serve as an excellent and cost-effective preliminary screening tool for developmental biologists working with a variety of experimental/disease models. PMID:25546089
Kline, Kay Setter; Scott, Linda D; Britton, Agnes S
2007-09-01
This study examined the effects of 2 home healthcare nursing approaches--supportive-educative and mutual goal setting--on self-management for patients with heart failure. Both approaches are specifically related to participants' understanding of heart failure and self-efficacy in managing the condition. An experimental, longitudinal, repeated-measures design was used with a sample of 88 participants. Although no significant difference was demonstrated in participants' understanding of heart failure, the supportive-educative group showed a significantly increased self-efficacy in managing heart failure symptoms.
Wu, Yanqing; Reece, E Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R; Yang, Peixin
2016-09-01
Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects remain largely unknown. We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects. A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene expression; and XBP1 messenger RNA splicing, as well as increased cleaved caspase 3 and 8 in embryonic hearts. Furthermore, maternal type 2 diabetes mellitus triggered excessive apoptosis in ventricular myocardium, endocardial cushion, and outflow tract of the embryonic heart. Similar to those observations in type 1 diabetic embryopathy, maternal type 2 diabetes mellitus causes heart defects in the developing embryo manifested with oxidative stress, endoplasmic reticulum stress, and excessive apoptosis in heart cells. Copyright © 2016 Elsevier Inc. All rights reserved.
Repeated recall as an intervention to improve memory performance in heart failure patients.
Viveiros, Jennifer; Sethares, Kristen; Shapiro, Amy
2017-12-01
Up to 50% of heart failure patients demonstrate aspects of cognitive impairment, including memory deficit. Novel interventions are needed to address memory deficit among heart failure patients. The goal of this study was to evaluate the testing effect as an intervention to improve memory performance in heart failure patients. This was a randomized controlled clinical trial ( N=84) comparing the memory performance of heart failure patients with and without mild cognitive impairment after a repeated testing intervention. Memory performance was measured by verbal word pair associates recall scores, between attention control and experimental subjects. Patients had a mean age of 71.7 ± 13.3 years and similar baseline memory (immediate p=.79 and delayed p=.47). Overall, there were no significant differences in memory between experimental and control subjects, respectively (67.2±18.87 vs. 61.9±22.3, verbal word pair associates, t = -1.179, p=.24). In the final hierarchical regression model, age ( p=.018) and education ( p=.006) were significant predictors of memory performance, with the intervention approaching significance ( p=.079). Although not statistically significant, the intervention group reported better memory. Age and education continue to be significant contributors to memory performance in the heart failure population. Continued development of interventions to improve memory performance in heart failure patients is indicated.
Espino, Daniel M; Shepherd, Duncan E T; Hukins, David W L
2014-01-01
A transient multi-physics model of the mitral heart valve has been developed, which allows simultaneous calculation of fluid flow and structural deformation. A recently developed contact method has been applied to enable simulation of systole (the stage when blood pressure is elevated within the heart to pump blood to the body). The geometry was simplified to represent the mitral valve within the heart walls in two dimensions. Only the mitral valve undergoes deformation. A moving arbitrary Lagrange-Euler mesh is used to allow true fluid-structure interaction (FSI). The FSI model requires blood flow to induce valve closure by inducing strains in the region of 10-20%. Model predictions were found to be consistent with existing literature and will undergo further development.
He, Yanyu; Yu, Sijiu; Hu, Junwei; Cui, Yan; Liu, Penggang
2016-01-01
The study aimed to identify the changes of anatomic and microscopic structure and the expression and localization of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in the myocardium and coronary artery of the yak heart adapted to chronic hypoxia with aging. Thirty-two yaks (1 day, 6 months, 1 year, 2 years, and 5 year old) were included, and immunoelectronmicroscopy, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used. Right ventricular hypertrophy was not present in yaks with aging. There was no intima thickening phenomenon in the coronary artery. The ultrastructure of myofibrils, mitochondria, and collagen fibers and the diameter and quantity of collagen changed significantly with aging. The enzymatic activity of complexes I, II, and V increased with age. Immunogold labeling showed the localization of HIF-1α protein in the cytoplasm and nuclei of endothelial cells and cytoplasm of cardiac muscle cells, and VEGF protein in the nuclei and perinuclei areas of smooth muscle cells of coronary artery, and in the cytoplasm and nuclei of endothelial cells. ELISA results showed that HIF-1α secretion significantly increased in the myocardium and coronary artery from an age of 1 day to 2 years of yaks and decreased in old yaks. However, VEGF protein always increased with aging. The findings of this study suggest that 6 months is a key age of yak before which there are some adaptive changes to deal with low-oxygen environment, and there is a maturation of the yak heart from the age of 6 months to 2 years. PMID:26914488
de Moraes, Wilson Max Almeida Monteiro; Melara, Thaís Plasti; de Souza, Pamella Ramona Moraes; de Salvi Guimarães, Fabiana; Bozi, Luiz Henrique Marchesi; Brum, Patricia Chakur; Medeiros, Alessandra
2015-01-01
Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α2A/α2CARKO treated with placebo and sedentary (KO, n = 9), α2A/α2CARKO treated with leucine and sedentary (KOL, n = 11), α2A/α2CARKO treated with placebo and AET (KOT, n = 12) or α2A/α2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes’ diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle. PMID:25988767
Gaiotto, F A; Grattapaglia, D; Vencovsky, R
2003-01-01
We report a detailed analysis of the population genetic structure, mating system, and gene flow of heart of palm (Euterpe edulis Mart.-Arecaceae) in central Brazil. This palm is considered a keystone species because it supplies fruits for birds and rodents all year and is intensively harvested for culinary purposes. Two populations of this palm tree were examined, using 18 microsatellite loci. The species displays a predominantly outcrossed mating system (tm = 0.94), with a probability of full sibship greater than 70% within open-pollinated families. The following estimates of interpopulation genetic variation were calculated and found significant: FIT = 0.17, FIS = 0.12, FST = 0.06, and RST = 0.07. This low but significant level of interpopulation genetic variation indicates high levels of gene flow. Two adult trees were identified as likely seed parents (P > 99.9%) of juveniles located at a distance of 22 km. Gene flow over such distances has not been reported before for tropical tree species. The establishment and management of in situ genetic reserves or ex situ conservation and breeding populations for E. edulis should contemplate the collection of several hundreds open-pollinated maternal families from relatively few distant populations to maximize the genetic sampling of a larger number of pollen parents.
Kitahara, Hideki; Okada, Kozo; Tanaka, Shigemitsu; Yang, Hyoung-Mo; Miki, Kojiro; Kobayashi, Yuhei; Kimura, Takumi; Luikart, Helen; Yock, Paul G; Yeung, Alan C; Fitzgerald, Peter J; Khush, Kiran K; Fearon, William F; Honda, Yasuhiro
2016-06-01
This study investigated the relationship between periarterial neovascularization, development of cardiac allograft vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested. Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures <1 mm in diameter, located ≤2 mm outside of the external elastic membrane. The signal void structures were excluded when they connected to the coronary lumen (considered as side branches) or could not be followed in ≥3 contiguous frames. The number of PSV was counted at 1-mm intervals throughout the first 50 mm of the left anterior descending artery, and the PSV score was calculated as the sum of cross-sectional values. Patients with a PSV score increase of ≥ 4 between baseline and 1-year post-transplant were classified as the "proliferative" group. Maximum intimal thickness was measured for the entire analysis segment. During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p < 0.001) and had a higher incidence of acute cellular rejection (50.0% vs 23.9%, p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036). The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Zito, Concetta; Mohammed, Moemen; Todaro, Maria Chiara; Khandheria, Bijoy K; Cusmà-Piccione, Maurizio; Oreto, Giuseppe; Pugliatti, Pietro; Abusalima, Mohamed; Antonini-Canterin, Francesco; Vriz, Olga; Carerj, Scipione
2014-11-01
We evaluated the interplay between left ventricular diastolic function and large-artery stiffness in asymptomatic patients at increased risk of heart failure and no structural heart disease (Stage A). We divided 127 consecutive patients (mean age 49 ± 17 years) with risk factors for heart failure who were referred to our laboratory to rule out structural heart disease into two groups according to presence (Group 1, n = 35) or absence (Group 2, n = 92) of grade I left ventricular diastolic dysfunction. Doppler imaging with high-resolution echo-tracking software was used to measure intima-media thickness (IMT) and stiffness of carotid arteries. Group 1 had significantly higher mean age, blood pressure, left ventricular mass index, carotid IMT and arterial stiffness than Group 2 (P < 0.05). Overall, carotid stiffness indices (β-stiffness index, augmentation index and elastic modulus) and 'one-point' pulse wave velocity each showed inverse correlation with E-wave velocity, E' velocity and E/A ratio, and direct correlation with A-wave velocity, E-wave deceleration time and E/E' ratio (P < 0.05). Arterial compliance showed negative correlations with the echocardiographic indices of left ventricular diastolic function (P < 0.05). On logistic regression analysis, age, hypertension, SBP, pulse pressure, left ventricular mass index, carotid IMT and stiffness parameters were associated with grade I left ventricular diastolic dysfunction (P < 0.05 for each). However, on multivariate logistic analysis, only 'one-point' pulse wave velocity and age were independent predictors (P = 0.038 and P = 0.016, respectively). An independent association between grade I left ventricular diastolic dysfunction and increased arterial stiffness is demonstrated at the earliest stage of heart failure. Hence, assessment of vascular function, beyond cardiac function, should be included in a comprehensive clinical evaluation of these patients.
Whittington, Hannah J; Ostrowski, Philip J; McAndrew, Debra J; Cao, Fang; Shaw, Andrew; Eykyn, Thomas R; Lake, Hannah; Tyler, Jack; Schneider, Jurgen E; Neubauer, Stefan; Zervou, Sevasti; Lygate, Craig A
2018-03-02
Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesised that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury. Mice were created overexpressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates. MtCK activity was 27% higher than WT, with no change in other CK isoenzymes or creatine levels. Electron microscopy confirmed normal mitochondrial cell density and mitochondrial localisation of transgenic protein. Respiration in isolated mitochondria was unaltered and metabolomic analysis by 1H-NMR suggests that cellular metabolism was not grossly affected by transgene expression. There were no significant differences in cardiac structure or function under baseline conditions by cine-MRI or LV haemodynamics. In Langendorff-perfused hearts subjected to 20min ischaemia and 30 min reperfusion, MtCK-OE exhibited less ischaemic contracture and improved functional recovery (Rate pressure product 58% above WT; P < 0.001). These hearts had reduced myocardial infarct size, which was confirmed in vivo: 55±4% in WT vs 29±4% in MtCK-OE; P < 0.0001). Isolated cardiomyocytes from MtCK-OE hearts exhibited delayed opening of the mitochondrial permeability transition pore (mPTP) compared to WT, which was confirmed by reduced mitochondrial swelling in response to calcium. There was no detectable change in the structural integrity of the mitochondrial membrane. Modest elevation of MtCK activity in the heart does not adversely affect cellular metabolism, mitochondrial or in vivo cardiac function, but modifies mPTP opening to protect against I/R injury and improve functional recovery. Our findings support MtCK as a prime therapeutic target in myocardial ischaemia.
Pouleur, Anne-Catherine; Anker, Stefan; Brito, Dulce; Brosteanu, Oana; Hasenclever, Dirk; Casadei, Barbara; Edelmann, Frank; Filippatos, Gerasimos; Gruson, Damien; Ikonomidis, Ignatios; Lhommel, Renaud; Mahmod, Masliza; Neubauer, Stefan; Persu, Alexandre; Gerber, Bernhard L; Piechnik, Stefan; Pieske, Burkert; Pieske-Kraigher, Elisabeth; Pinto, Fausto; Ponikowski, Piotr; Senni, Michele; Trochu, Jean-Noël; Van Overstraeten, Nancy; Wachter, Rolf; Balligand, Jean-Luc
2018-06-22
Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β 3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e' ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
Yoon, Sung Sug Sarah; Dillon, Charles F; Illoh, Kachi; Carroll, Margaret
2016-10-01
This study evaluated recent trends in the prevalence of coronary heart disease in the U.S. population aged ≥40 years. A total of 21,472 adults aged ≥40 years from the 2001-2012 National Health and Nutrition Examination Survey were included in the analysis. The analysis was conducted in 2015. Coronary heart disease included myocardial infarction, angina, and any other type of coronary heart disease, which were defined as a history of medical diagnosis of these specific conditions. Angina was also defined as currently taking anti-angina medication or having Rose Angina Questionnaire responses that scored with a Grade ≥1. Trends from 2001 to 2012 were analyzed overall, within demographic subgroups, and by major coronary heart disease risk factors. Between 2001 and 2012, the overall prevalence of coronary heart disease significantly decreased from 10.3% to 8.0% (p-trend<0.05). The prevalence of angina significantly decreased from 7.8% to 5.5% and myocardial infarction prevalence decreased from 5.5% to 4.7% (p-trend <0.05 for both groups). Overall coronary heart disease prevalence significantly decreased among women, adults aged >60 years, non-Hispanic whites, non-Hispanic blacks, adults who did not complete high school, adults with more than a high school education, and adults who had health insurance (p-trend <0.05 for all groups). The overall prevalence of coronary heart disease including angina and myocardial infarction decreased significantly over the 12-year survey period. However, this reduction was seen mainly among persons without established coronary heart disease risk factors. There was no change in coronary heart disease prevalence among those with specific coronary heart disease risk factors. Published by Elsevier Inc.
Anger, hostility, and hospitalizations in patients with heart failure.
Keith, Felicia; Krantz, David S; Chen, Rusan; Harris, Kristie M; Ware, Catherine M; Lee, Amy K; Bellini, Paula G; Gottlieb, Stephen S
2017-09-01
Heart failure patients have a high hospitalization rate, and anger and hostility are associated with coronary heart disease morbidity and mortality. Using structural equation modeling, this prospective study assessed the predictive validity of anger and hostility traits for cardiovascular and all-cause rehospitalizations in patients with heart failure. 146 heart failure patients were administered the STAXI and Cook-Medley Hostility Inventory to measure anger, hostility, and their component traits. Hospitalizations were recorded for up to 3 years following baseline. Causes of hospitalizations were categorized as heart failure, total cardiac, noncardiac, and all-cause (sum of cardiac and noncardiac). Measurement models were separately fit for Anger and Hostility, followed by a Confirmatory Factor Analysis to estimate the relationship between the Anger and Hostility constructs. An Anger model consisted of State Anger, Trait Anger, Anger Expression Out, and Anger Expression In, and a Hostility model included Cynicism, Hostile Affect, Aggressive Responding, and Hostile Attribution. The latent construct of Anger did not predict any of the hospitalization outcomes, but Hostility significantly predicted all-cause hospitalizations. Analyses of individual trait components of each of the 2 models indicated that Anger Expression Out predicted all-cause and noncardiac hospitalizations, and Trait Anger predicted noncardiac hospitalizations. None of the individual components of Hostility were related to rehospitalizations or death. The construct of Hostility and several components of Anger are predictive of hospitalizations that were not specific to cardiac causes. Mechanisms common to a variety of health problems, such as self-care and risky health behaviors, may be involved in these associations. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio
2011-01-01
It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.
Impact of age and sex on normal left heart structure and function.
Hagström, Linn; Henein, Michael Y; Karp, Kjell; Waldenström, Anders; Lindqvist, Per
2017-11-01
Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose. We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions. Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years. Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.
Congenital heart disease linked to maternal autoimmunity against cardiac myosin.
Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz
2014-05-01
Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.
Medzihradszky, K F; Gibson, B W; Kaur, S; Yu, Z H; Medzihradszky, D; Burlingame, A L; Bass, N M
1992-02-01
The primary structure of a fatty-acid-binding protein (FABP) isolated from the liver of the nurse shark (Ginglymostoma cirratum) was determined by high-performance tandem mass spectrometry (employing multichannel array detection) and Edman degradation. Shark liver FABP consists of 132 amino acids with an acetylated N-terminal valine. The chemical molecular mass of the intact protein determined by electrospray ionization mass spectrometry (Mr = 15124 +/- 2.5) was in good agreement with that calculated from the amino acid sequence (Mr = 15121.3). The amino acid sequence of shark liver FABP displays significantly greater similarity to the FABP expressed in mammalian heart, peripheral nerve myelin and adipose tissue (61-53% sequence similarity) than to the FABP expressed in mammalian liver (22% similarity). Phylogenetic trees derived from the comparison of the shark liver FABP amino acid sequence with the members of the mammalian fatty-acid/retinoid-binding protein gene family indicate the initial divergence of an ancestral gene into two major subfamilies: one comprising the genes for mammalian liver FABP and gastrotropin, the other comprising the genes for mammalian cellular retinol-binding proteins I and II, cellular retinoic-acid-binding protein myelin P2 protein, adipocyte FABP, heart FABP and shark liver FABP, the latter having diverged from the ancestral gene that ultimately gave rise to the present day mammalian heart-FABP, adipocyte FABP and myelin P2 protein sequences. The sequence for intestinal FABP from the rat could be assigned to either subfamily, depending on the approach used for phylogenetic tree construction, but clearly diverged at a relatively early evolutionary time point. Indeed, sequences proximately ancestral or closely related to mammalian intestinal FABP, liver FABP, gastrotropin and the retinoid-binding group of proteins appear to have arisen prior to the divergence of shark liver FABP and should therefore also be present in elasmobranchs. The presence in shark liver of an FABP which differs substantially in primary structure from mammalian liver FABP, while being closely related to the FABP expressed in mammalian heart muscle, peripheral nerve myelin and adipocytes, opens a further dimension regarding the question of the existence of structure-dependent and tissue-specific specialization of FABP function in lipid metabolism.
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.
Li, Aiyan; Kuga, Keisuke; Suzuki, Akihiro; Endo, Masae; Niho, Bumpei; Enomoto, Mami; Kanemoto, Miyako; Yamaguchi, Iwao
2002-01-01
Heart rate is largely affected by the autonomic nervous system. However, little is known about the anatomic pathway of autonomic nerve fibers innervating the sinus node. The present study: (1) evaluates the effects of cavotricuspid isthmus ablation for common atrial flutter (AFL) on autonomic nervous function by using heart rate variability analysis, and (2) investigates the distribution of autonomic nerve pathways innervating the sinus node. Twelve patients with paroxysmal common atrial flutter who maintained sinus rhythm both before and after radiofrequency ablation were selected for the study. Holter ambulatory recordings were performed before and after (2.3 +/- 1.0 days) radiofrequency ablation of cavotricuspid isthmus. Heart rate and time domain (SDANN, rMSSD, pNN50) and frequency domain (low frequency (LF), high frequency (HF), LF/HF) analysis of heart rate variability were compared before and after ablation. Mean heart rate did not change significantly after ablation (59 +/- 6 vs 61 +/- 9 beats/min); parasympathetic indices of heart rate variability (SDANN, rMSSD, pNN50, HF) did not change significantly (110 +/- 37 vs 117 +/- 20 ms; 32 +/- 21 vs 28 +/- 9 ms; 4.8 +/- 0.9 vs 4.7 +/- 0.71n(ms2)); and sympathetic indices of heart rate variability (LF/HF) did not change significantly (1.1 +/- 0.2 vs 1.2 +/- 0.1). Cavotricuspid isthmus ablation for atrial flutter did not significantly change heart rate and heart rate variability because parasympathetic and sympathetic fibers innervating the sinus node are scarce in this region.
Oh, Myung Ok; Kim, Young Jeoum; Baek, Cho Hee; Kim, Ju Hee; Park, No Mi; Yu, Mi Jeong; Song, Han Sol
2016-06-01
The purpose of this cross-over experimental study was to examine effects of music intervention on maternal anxiety, fetal heart rate pattern and testing time during non-stress tests (NST) for antenatal fetal assessment. Sixty pregnant women within 28 to 40 gestational weeks were randomly assigned to either the experimental group (n=30) or control group (n=30). Music intervention was provided to pregnant women in the experimental group during NST. Degree of maternal anxiety and fetal heart rate pattern were our primary outcomes. State-trait anxiety inventory, blood pressure, pulse rate, and changes in peripheral skin temperature were assessed to determine the degree of maternal anxiety. Baseline fetal heart rate, frequency of acceleration in fetal heart rate, fetal movement test and testing time for reactive NST were assessed to measure the fetal heart rate pattern. The experimental group showed significantly lower scores in state anxiety than the control group. There were no significant differences in systolic blood pressure and pulse rate between the two groups. Baseline fetal heart rate was significantly lower in the experimental group than in the control group. Frequency of acceleration in fetal heart rate was significantly increased in the experimental group compared to the control group. There were no significant differences in fetal movement and testing time for reactive NST between the two groups. Present results suggest that music intervention could be an effective nursing intervention for alel viating anxiety during non-stress test.
Baker, Jacquie; Racosta, Juan M; Balint, Brittany; Kimpinski, Kurt
2018-03-01
The clinical significance of heart rate variability in the context of autonomic dysfunction continues to be a matter of debate. A consensus is lacking on the best heart rate variability measures for clinical purposes. Therefore, the purpose of this study was to investigate the utility of heart rate variability parameters in healthy versus autonomic dysfunction. Healthy young (n = 134), healthy older (n = 32), and patients with mild (postural tachycardia syndrome; n = 25) and severe (neurogenic orthostatic hypotension; n = 34) autonomic dysfunction were included. Time and frequency parameters during baseline, head-up tilt (HUT), and heart rate response to deep breathing (HRDB) were compared. Cardiovagal time parameters were significantly reduced during HUT in healthy young and postural tachycardia syndrome (P < 0.001). Healthy young had significantly higher time parameters during baseline, HUT, and HRDB (P < 0.01). This was reflected by a significantly lower resting heart rate (HR) (61.4 ± 9.0 bpm vs. 76.8 ± 13.6 bpm; P < 0.001) and a smaller [INCREMENT]HR during HUT (32.8 ± 10.5 bpm vs. 44.4 ± 13.3 bpm; P < 0.001). Time parameters increased in young and postural tachycardia syndrome during HRDB, which was characterized by a nonsignificant difference in [INCREMENT]HR between both groups. Time parameters were significantly higher in healthy old versus neurogenic orthostatic hypotension at rest and during HRDB (P < 0.05). During HUT, only the SD of all normal RR intervals remained significantly higher. Heart rate changes corroborated these findings. Resting HR was significantly lower in healthy older (62.6 ± 11.0 bpm vs. 70.7 ± 12.4 bpm), and [INCREMENT]HR during HRDB was significantly higher (15.9 ± 9.2 bpm vs. 3.9 ± 4.2 bpm; P < 0.001). During HUT, [INCREMENT]HR showed no significant differences. Time domain parameters of heart rate variability have a greater utility than frequency parameters in clinical autonomic disorders.
[A rare cause of heart failure].
Gutersohn, Andreas; Oestmann, Andreas
2014-12-10
We report the case of a 52 years old patient with dilated cardiomyopathy. Ischemic heart disease was excluded by coronary angiography. However, bilateral hilar lymphadenopathy was present on plain chest radiography. Transbronchial biopsy showed non-necrotizing, epitheloid cell granulomas and thus sarcoidosis was diagnosed. A MRI of the heart confirmed the cardiac involvement by the sarcoidosis with corresponding structural changes.
Dynamic Imaging of Mouse Embryos and Cardiodynamics in Static Culture.
Lopez, Andrew L; Larina, Irina V
2018-01-01
The heart is a dynamic organ that quickly undergoes morphological and mechanical changes through early embryonic development. Characterizing these early moments is important for our understanding of proper embryonic development and the treatment of heart disease. Traditionally, tomographic imaging modalities and fluorescence-based microscopy are excellent approaches to visualize structural features and gene expression patterns, respectively, and connect aberrant gene programs to pathological phenotypes. However, these approaches usually require static samples or fluorescent markers, which can limit how much information we can derive from the dynamic and mechanical changes that regulate heart development. Optical coherence tomography (OCT) is unique in this circumstance because it allows for the acquisition of three-dimensional structural and four-dimensional (3D + time) functional images of living mouse embryos without fixation or contrast reagents. In this chapter, we focus on how OCT can visualize heart morphology at different stages of development and provide cardiodynamic information to reveal mechanical properties of the developing heart.
Low-cost compact ECG with graphic LCD and phonocardiogram system design.
Kara, Sadik; Kemaloğlu, Semra; Kirbaş, Samil
2006-06-01
Till today, many different ECG devices are made in developing countries. In this study, low cost, small size, portable LCD screen ECG device, and phonocardiograph were designed. With designed system, heart sounds that take synchronously with ECG signal are heard as sensitive. Improved system consist three units; Unit 1, ECG circuit, filter and amplifier structure. Unit 2, heart sound acquisition circuit. Unit 3, microcontroller, graphic LCD and ECG signal sending unit to computer. Our system can be used easily in different departments of the hospital, health institution and clinics, village clinic and also in houses because of its small size structure and other benefits. In this way, it is possible that to see ECG signal and hear heart sounds as synchronously and sensitively. In conclusion, heart sounds are heard on the part of both doctor and patient because sounds are given to environment with a tiny speaker. Thus, the patient knows and hears heart sounds him/herself and is acquainted by doctor about healthy condition.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Smyth, Lloyd M, E-mail: lloyd.smyth@epworth.org.au; Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, School of Biomedical Sciences, Nursing and Health Sciences, Monash University, Clayton, Victoria; Knight, Kellie A
Despite technical advancements in breast radiation therapy, cardiac structures are still subject to significant levels of irradiation. As the use of adjuvant radiation therapy after breast-conserving surgery continues to improve survival for early breast cancer patients, the associated radiation-induced cardiac toxicities become increasingly relevant. Our primary aim was to evaluate the cardiac-sparing benefits of the deep inspiration breath-hold (DIBH) technique. An electronic literature search of the PubMed database from 1966 to July 2014 was used to identify articles published in English relating to the dosimetric benefits of DIBH. Studies comparing the mean heart dose of DIBH and free breathing treatmentmore » plans for left breast cancer patients were eligible to be included in the review. Studies evaluating the reproducibility and stability of the DIBH technique were also reviewed. Ten studies provided data on the benefits of DIBH during left breast irradiation. From these studies, DIBH reduced the mean heart dose by up to 3.4 Gy when compared to a free breathing approach. Four studies reported that the DIBH technique was stable and reproducible on a daily basis. According to current estimates of the excess cardiac toxicity associated with radiation therapy, a 3.4 Gy reduction in mean heart dose is equivalent to a 13.6% reduction in the projected increase in risk of heart disease. DIBH is a reproducible and stable technique for left breast irradiation showing significant promise in reducing the late cardiac toxicities associated with radiation therapy.« less
Living nano-micro fibrous woven fabric/hydrogel composite scaffolds for heart valve engineering.
Wu, Shaohua; Duan, Bin; Qin, Xiaohong; Butcher, Jonathan T
2017-03-15
Regeneration and repair of injured or diseased heart valves remains a clinical challenge. Tissue engineering provides a promising treatment approach to facilitate living heart valve repair and regeneration. Three-dimensional (3D) biomimetic scaffolds that possess heterogeneous and anisotropic features that approximate those of native heart valve tissue are beneficial to the successful in vitro development of tissue engineered heart valves (TEHV). Here we report the development and characterization of a novel composite scaffold consisting of nano- and micro-scale fibrous woven fabrics and 3D hydrogels by using textile techniques combined with bioactive hydrogel formation. Embedded nano-micro fibrous scaffolds within hydrogel enhanced mechanical strength and physical structural anisotropy of the composite scaffold (similar to native aortic valve leaflets) and also reduced its compaction. We determined that the composite scaffolds supported the growth of human aortic valve interstitial cells (HAVIC), balanced the remodeling of heart valve ECM against shrinkage, and maintained better physiological fibroblastic phenotype in both normal and diseased HAVIC over single materials. These fabricated composite scaffolds enable the engineering of a living heart valve graft with improved anisotropic structure and tissue biomechanics important for maintaining valve cell phenotypes. Heart valve-related disease is an important clinical problem, with over 300,000 surgical repairs performed annually. Tissue engineering offers a promising strategy for heart valve repair and regeneration. In this study, we developed and tissue engineered living nano-micro fibrous woven fabric/hydrogel composite scaffolds by using textile technique combined with bioactive hydrogel formation. The novelty of our technique is that the composite scaffolds can mimic physical structure anisotropy and the mechanical strength of natural aortic valve leaflet. Moreover, the composite scaffolds prevented the matrix shrinkage, which is major problem that causes the failure of TEHV, and better maintained physiological fibroblastic phenotype in both normal and diseased HAVIC. This work marks the first report of a combination composite scaffold using 3D hydrogel enhanced by nano-micro fibrous woven fabric, and represents a promising tissue engineering strategy to treat heart valve injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Perring, S; Jones, E
2003-08-01
Instantaneous heart rate and chest wall motion were measured using a 3-lead ECG and an air pressure chest wall plethysmography system. Chest wall plethysmography traces were found to accurately represent the breathing pattern as measured by spirometry (average correlation coefficient 0.944); though no attempt was made to calibrate plethysmography voltage output to tidal volume. Simultaneous measurements of heart rate and chest wall motion were made for short periods under metronome guided breathing at 6 breaths per minute. The average peak to trough heart rate change per breath cycle (AVEMAX) and maximum correlation between heart rate and breathing cycle (HRBRCORR) were measured. Studies of 44 normal volunteers indicated clear inverse correlation of heart rate variability parameters with age (AVEMAX R = -0.502, P < 0.001) but no significant change in HRBRCORR with age (R = -0.115). Comparison of normal volunteers with diabetics with no history of symptoms associated with autonomic failure indicated significant lower heart rate variability in diabetics (P = 0.005 for AVEMAX) and significantly worse correlation between heart rate and breathing (P < 0.001 for HRBRCORR). Simultaneous measurement of heart rate and breathing offers the possibility of more sensitive diagnosis of autonomic failure in a simple bedside test and gives further insight into the nature of cardio-ventilatory coupling.
Lewis, Martin; Szobi, Adrian; Balaska, Dirki; Khaliulin, Igor; Adameova, Adriana; Griffiths, Elinor; Orchard, Clive H; Suleiman, M-Saadeh
2018-02-07
Consecutive treatment of adult rat heart with isoproterenol and adenosine (Iso/Aden), known to consecutively activate PKA/PKC signaling, is cardioprotective against ischemia and reperfusion (I/R). Whether this is cardioprotective in an immature heart is unknown. Langendorff-perfused hearts from adult and immature (60 and 14 days old) male Wistar rats were exposed to 30 min ischemia and 120 min reperfusion, with or without prior perfusion with 5 nM Iso for 3 min followed by 30 μM Aden for 5 min. Changes in hemodynamics (developed pressure and coronary flow) and cardiac injury (Lactate Dehydrogenase (LDH) release and infarct size) were measured. Additional hearts were used to measure glycogen content. Iso induced a similar inotropic response in both age groups. Treatment with Iso/Aden resulted in a significant reduction in time to the onset of ischemic contracture in both age groups whilst time to peak contracture was significantly shorter only in immature hearts. Upon reperfusion, the intervention reduced cardiac injury and functional impairment in adults with no protection of immature heart. Immature hearts have significantly less glycogen content compared to adult. This work shows that Iso/Aden perfusion confers protection in an adult heart but not in an immature heart. It is likely that metabolic differences including glycogen content contribute to this difference.
Szobi, Adrian; Balaska, Dirki; Khaliulin, Igor; Adameova, Adriana; Griffiths, Elinor; Orchard, Clive H.; Suleiman, M.-Saadeh
2018-01-01
Consecutive treatment of adult rat heart with isoproterenol and adenosine (Iso/Aden), known to consecutively activate PKA/PKC signaling, is cardioprotective against ischemia and reperfusion (I/R). Whether this is cardioprotective in an immature heart is unknown. Langendorff–perfused hearts from adult and immature (60 and 14 days old) male Wistar rats were exposed to 30 min ischemia and 120 min reperfusion, with or without prior perfusion with 5 nM Iso for 3 min followed by 30 μM Aden for 5 min. Changes in hemodynamics (developed pressure and coronary flow) and cardiac injury (Lactate Dehydrogenase (LDH) release and infarct size) were measured. Additional hearts were used to measure glycogen content. Iso induced a similar inotropic response in both age groups. Treatment with Iso/Aden resulted in a significant reduction in time to the onset of ischemic contracture in both age groups whilst time to peak contracture was significantly shorter only in immature hearts. Upon reperfusion, the intervention reduced cardiac injury and functional impairment in adults with no protection of immature heart. Immature hearts have significantly less glycogen content compared to adult. This work shows that Iso/Aden perfusion confers protection in an adult heart but not in an immature heart. It is likely that metabolic differences including glycogen content contribute to this difference. PMID:29414860
Restoration of heart functions using human embryonic stem cells derived heart muscle cells.
Gepstein, Lior; Kehat, Izhak
2005-02-01
Extract: Recent advances in molecular and cellular biology and specifically in the areas of stem cell biology and tissue engineering have paved the way for the development of a new field in biomedicine, regenerative medicine. This exciting approach seeks to develop new biological solutions, using the mobilization of endogenous stem cells or delivery of exogenous cells to replace or modify the function of diseased, absent, or malfunctioning tissue. The adult heart represents an attractive candidate for these emerging technologies, since adult cardiomyocytes have limited regenerative capacity. Thus, any significant heart cell loss or dysfunction, such as occurs during heart attack, is mostly irreversible and may lead to the development of progressive heart failure, one of the leading causes of world-wide morbidity and mortality. Similarly, dysfunction of the specialized electrical conduction system within the heart may result in inefficient rhythm initiation or impulse conduction, leading to significant slowing of the heart rate, usually requiring the implantation of a permanent electronic pacemaker. Replacement of the dysfunctional myocardium (heart muscle) by implantation of external heart muscle cells is emerging as a novel paradigm for restoration of the myocardial electromechanical properties, but has been significantly hampered by the paucity of cell sources for human heart cells and by the relatively limited evidence for functional integration between grafted and host cells. The recently described human embryonic stem cell (hESC) lines may provide a possible solution for the aforementioned cell sourcing problem.
Benoist, David; Stones, Rachel; Benson, Alan P.; Fowler, Ewan D.; Drinkhill, Mark J.; Hardy, Matthew E.L.; Saint, David A.; Cazorla, Olivier; Bernus, Olivier; White, Ed
2014-01-01
We demonstrate the synergistic benefits of using multiple technologies to investigate complex multi-scale biological responses. The combination of reductionist and integrative methodologies can reveal novel insights into mechanisms of action by tracking changes of in vivo phenomena to alterations in protein activity (or vice versa). We have applied this approach to electrical and mechanical remodelling in right ventricular failure caused by monocrotaline-induced pulmonary artery hypertension in rats. We show arrhythmogenic T-wave alternans in the ECG of conscious heart failure animals. Optical mapping of isolated hearts revealed discordant action potential duration (APD) alternans. Potential causes of the arrhythmic substrate; structural remodelling and/or steep APD restitution and dispersion were observed, with specific remodelling of the Right Ventricular Outflow Tract. At the myocyte level, [Ca2+]i transient alternans were observed together with decreased activity, gene and protein expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA). Computer simulations of the electrical and structural remodelling suggest both contribute to a less stable substrate. Echocardiography was used to estimate increased wall stress in failure, in vivo. Stretch of intact and skinned single myocytes revealed no effect on the Frank-Starling mechanism in failing myocytes. In isolated hearts acute stretch-induced arrhythmias occurred in all preparations. Significant shortening of the early APD was seen in control but not failing hearts. These observations may be linked to changes in the gene expression of candidate mechanosensitive ion channels (MSCs) TREK-1 and TRPC1/6. Computer simulations incorporating MSCs and changes in ion channels with failure, based on altered gene expression, largely reproduced experimental observations. PMID:25016242
Sánchez Ferrer, Francisco; Sánchez Ferrer, María Luisa; Grima Murcia, María Dolores; Sánchez Ferrer, Marina; Sánchez del Campo, Francisco
2015-08-01
Left ventricular false tendon is a structure of unknown function in cardiac physiology that was first described anatomically by Turner. This condition may be related to various electrical or functional abnormalities, but no consensus has ever been reached. The purpose of this study was to determine the time of appearance, prevalence and histologic composition of false tendon, as well as its association with innocent murmur in children and with heart disease. The basic research was performed by anatomic dissection of hearts from adult human cadavers to describe false tendon and its histology. The clinical research consisted of echocardiographic study in a pediatric population to identify any relationship with heart disease, innocent murmur in children, or other abnormalities. Fetal echocardiography was performed prenatally at different gestational ages. False tendon was a normal finding in cardiac dissection and was composed of muscle and connective tissue fibers. In the pediatric population, false tendon was present in 83% on echocardiography and showed a statistically significant association only with innocent murmur in children and slower aortic acceleration. The presence of false tendon was first observed on fetal echocardiography from week 20 of pregnancy. Left ventricular false tendon is a normal finding visualized by fetal echocardiography from week 20 and is present until adulthood with no pathologic effects except for innocent murmur during childhood. It remains to be determined if false tendon is the cause of the murmurs or if its absence or structural anomalies are related to disease. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
L-type Ca2+ channels in the heart: structure and regulation.
Treinys, Rimantas; Jurevicius, Jonas
2008-01-01
This review analyzes the structure and regulation mechanisms of voltage-dependent L-type Ca(2+) channel in the heart. L-type Ca(2+) channels in the heart are composed of four different polypeptide subunits, and the pore-forming subunit alpha(1) is the most important part of the channel. In cardiac myocytes, Ca(2+) enter cell cytoplasm from extracellular space mainly through L-type Ca(2+) channels; these channels are very important system in heart Ca(2+) uptake regulation. L-type Ca(2+) channels are responsible for the activation of sarcoplasmic reticulum channels (RyR2) and force of muscle contraction generation in heart; hence, activity of the heart depends on L-type Ca(2+) channels. Phosphorylation of channel-forming subunits by different kinases is one of the most important ways to change the activity of L-type Ca(2+) channel. Additionally, the activity of L-type Ca(2+) channels depends on Ca(2+) concentration in cytoplasm. Ca(2+) current in cardiac cells can facilitate, and this process is regulated by phosphorylation of L-type Ca(2+) channels and intracellular Ca(2+) concentration. Disturbances in cellular Ca(2+) transport and regulation of L-type Ca(2+) channels are directly related to heart diseases, life quality, and life span.
Zheng, Xia; Hu, Shen-Jiang
2006-03-01
Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has long been thought to exert its benefits by reducing cholesterol synthesis, and has been shown to significantly reduce cardiovascular events and mortality in patients with or without coronary artery disease. However, it is still unknown whether acute administration of simvastatin beneficially affects the cardiac function prior or during ischemia-reperfusion. The aim of this study is to evaluate the cardioprotective effect of acute simvastatin treatment on isolated rat hearts or isolated ischemia-reperfusion hearts. Hearts were isolated from male Sprague-Dawley rats and attached to a Langendorff apparatus. The isolated hearts with or without ischemia (15 min) and reperfusion (60 min) were perfused with different concentrations of simvastatin. The parameters of cardiac function (such as left ventricular developed pressure [LVDP], +dp/dt max, and -dp/dt max), heart rate, and coronary flow were recorded. Simvastatin (3-30 micromol/l) significantly increased LVDP, +dp/dt max, and -dp/dt max in isolated rat hearts perfused for 60 min. Heart rate was depressed by 30 micromol/l simvastatin and the coronary flow was increased by 10 and 30 micromol/l simvastatin. At a concentration of 100 micromol/l simvastatin, worsening of heart function and subsequent cardiac arrest occurred. Administration of simvastatin (3-30 micromol/l) significantly preserved cardiac function detected by LVDP, +dp/dt max, and -dp/dt max in the isolated ischemia/reperfused (15/60 min) rat hearts. Simvastatin also significantly decreased heart rate at 30 micromol/l, and increased coronary flow at 10 and 30 micromol/l in these rat hearts. However, the protective effect of simvastatin reverted to increased damage at 100 micromol/l. Only 3 micromol/l simvastatin pretreatment before 15/60 min ischemia-reperfusion altered LVDP, +dp/dt max, and -dp/dt max. Both heart rate and coronary flow were unaltered after simvastatin pretreatment. Since simvastatin at a concentration lower than 100 micromol/l exerted beneficial effects on cardiac function in isolated perfused rat hearts, it could be applied just after myocardial ischemia and reperfusion.
CONGENITAL HEART MALFORMATIONS IN NEWBORN BABIES WITH LOW BIRTH WEIGHT.
Luca, Alina-Costina; Holoc, Andreea-Simona; Iordache, C
2015-01-01
Congenital heart malformations represent a public health problem, holding a significant percentage of the total of heart diseases. Beside the elevated frequency of the malformations, we also notice their occurrence in newborn babies with low birth weight, increasing, thus, the risk of complications and late therapeutic approach. The goal of the study was to highlight the general and particular aspects of cardiovascular malformations epidemiology in newborn babies with low weight at birth, the correlation of the malformations with implied genetic and environmental factors, assessing the complications and their procedures on the therapeutic management. Our study was performed on a group of 271 patients, hospitalized in the Department of Pediatric Cardiology of "Sf. Maria" Emergency Clinical Hospital for Children of Iasi, during January 2011-December 2013. The patients were assessed based on anamnesis, clinical, biological and imagistic exam. The study lot was divided according to the type of the structural defect: 95% of the patients were diagnosed with non-cyanogenic congenital heart malformations and 5% with cyanogenic congenital heart malformations. Regarding the patient's origin background, we notice an elevated frequency of the rural environment (71%). The incidence of the malformations was high in premature low birth weight (48%), followed by premature very low birth weight (22%). In evolution, congenital heart malformations often get more complicated heart failure, arterial hypertension and respiratory infections being most often met. Mortality was maximum in the first year of life, a third of the cases being associated with chromosomal malformations. Congenital heart malformations in newborn patients with low weight at birth represented an elevated percentage of 44.13% of the total of the cases hospitalized for cardiovascular diseases from the Department of Pediatric Cardiology of Iasi. Many cases were associated with other congenital malformations or different complications, being necessary an interdisciplinary collaboration to adequately monitor the anatom5ical and functional parameters and to ensure a somatic and mental development as normal as possible.
Music structure determines heart rate variability of singers
Vickhoff, Björn; Malmgren, Helge; Åström, Rickard; Nyberg, Gunnar; Ekström, Seth-Reino; Engwall, Mathias; Snygg, Johan; Nilsson, Michael; Jörnsten, Rebecka
2013-01-01
Choir singing is known to promote wellbeing. One reason for this may be that singing demands a slower than normal respiration, which may in turn affect heart activity. Coupling of heart rate variability (HRV) to respiration is called Respiratory sinus arrhythmia (RSA). This coupling has a subjective as well as a biologically soothing effect, and it is beneficial for cardiovascular function. RSA is seen to be more marked during slow-paced breathing and at lower respiration rates (0.1 Hz and below). In this study, we investigate how singing, which is a form of guided breathing, affects HRV and RSA. The study comprises a group of healthy 18 year olds of mixed gender. The subjects are asked to; (1) hum a single tone and breathe whenever they need to; (2) sing a hymn with free, unguided breathing; and (3) sing a slow mantra and breathe solely between phrases. Heart rate (HR) is measured continuously during the study. The study design makes it possible to compare above three levels of song structure. In a separate case study, we examine five individuals performing singing tasks (1–3). We collect data with more advanced equipment, simultaneously recording HR, respiration, skin conductance and finger temperature. We show how song structure, respiration and HR are connected. Unison singing of regular song structures makes the hearts of the singers accelerate and decelerate simultaneously. Implications concerning the effect on wellbeing and health are discussed as well as the question how this inner entrainment may affect perception and behavior. PMID:23847555
Zhao, Tiemin; Zhang, Dongsheng; Millard, Ronald W.; Ashraf, Muhammad; Wang, Yigang
2009-01-01
We used a heterotopic transplanted working heart model to probe the collaborative role of bone marrow-derived progenitor cells (BPCs) and stromal cell-derived factor (SDF)-1α in attenuating tissue remodeling in recipient and transplanted hearts. BPCs from male transgenic rats expressing green fluorescent protein (GFP+ BPCs, 2 × 106 cells) were injected intravenously into myeloablated female rats. One month later, heterotopic heart transplantation was performed. The left anterior descending coronary artery (LAD) of the recipient heart was occluded permanently. Mesenchymal stem cells (MSCs; 2 × 106 cells) with a null gene (null group) or overexpressing SDF-1α (SDF-1α group) were injected intramyocardially in the LAD perfusion region of both recipient and transplanted hearts. Recipient and transplanted hearts (n = 10 hearts/group) were harvested 21 days later for analysis. The survival of transplanted hearts was assessed daily by palpation in additional animals (n = 7). Five days after LAD occlusion, subpopulations of GFP+ BPCs in the circulation were significantly higher in the SDF-1α group. Y chromosome, 5-bromo-2′-deoxyuridine, Ki67-positive nuclei, newly formed vessels, and GFP+ cells significantly increased in transplanted hearts of the SDF-1α group at 21 days after the injection of MSCs overexpressing SDF-1α, whereas fewer TUNEL-positive nuclei were found. The survival of transplanted hearts was also markedly increased in the SDF-1α group (P < 0.05). Supplementation of endogenous cytokines released from the ischemic myocardium with exogenous MSCs overexpressing SDF-1α significantly increased BPC homing to acutely ischemic recipient and progressively ischemic transplanted hearts. BPC recruitment resulted in the regeneration of new cardiomyocytes and blood vessels and extended survival of the transplanted hearts. PMID:19181961
The Effect of Heart Disease on Anesthetic Complications During Routine Dental Procedures in Dogs.
Carter, Jennifer E; Motsinger-Reif, Alison A; Krug, William V; Keene, Bruce W
Dental procedures are a common reason for general anesthesia, and there is widespread concern among veterinarians that heart disease increases the occurrence of anesthetic complications. Anxiety about anesthetizing dogs with heart disease is a common cause of referral to specialty centers. To begin to address the potential effect of heart disease on anesthetic complications in dogs undergoing anesthesia for routine dental procedures, we compared anesthetic complications in 100 dogs with heart disease severe enough to trigger referral to a specialty center (cases) to those found in 100 dogs without cardiac disease (controls) that underwent similar procedures at the same teaching hospital. Medical records were reviewed to evaluate the occurrence of anesthetic complications. No dogs died in either group, and no significant differences were found between the groups in any of the anesthetic complications evaluated, although dogs in the heart disease group were significantly older with higher American Society of Anesthesiologists scores. Midazolam and etomidate were used more frequently, and alpha-2 agonists used less frequently, in the heart disease group compared to controls. This study suggests dogs with heart disease, when anesthetized by trained personnel and carefully monitored during routine dental procedures, are not at significantly increased risk for anesthetic complications.
Borneman, Tracy E.; Rose, Eli T.; Simons, Theodore R.
2014-01-01
An organism's heart rate is commonly used as an indicator of physiological stress due to environmental stimuli. We used heart rate to monitor the physiological response of American Oystercatchers (Haematopus palliatus) to human activity in their nesting environment. We placed artificial eggs with embedded microphones in 42 oystercatcher nests to record the heart rate of incubating oystercatchers continuously for up to 27 days. We used continuous video and audio recordings collected simultaneously at the nests to relate physiological response of birds (heart rate) to various types of human activity. We observed military and civilian aircraft, off-road vehicles, and pedestrians around nests. With the exception of high-speed, low-altitude military overflights, we found little evidence that oystercatcher heart rates were influenced by most types of human activity. The low-altitude flights were the only human activity to significantly increase average heart rates of incubating oystercatchers (12% above baseline). Although statistically significant, we do not consider the increase in heart rate during high-speed, low-altitude military overflights to be of biological significance. This noninvasive technique may be appropriate for other studies of stress in nesting birds.
Yu, Xinfeng; Zhang, Quanbin; Cui, Wentong; Zeng, Zheng; Yang, Wenzhe; Zhang, Chao; Zhao, Hongwei; Gao, Weidong; Wang, Xiaomin; Luo, Dali
2014-01-01
Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte apoptosis. Oxidative stress is suggested to be the major contributor to the development of DCM. This study was intended to evaluate the protective effect of low molecular weight fucoidan (LMWF) against cardiac dysfunction in diabetic rats. Type 2 diabetic goto-kakizaki rats were untreated or treated with LMWF (50 and 100 mg/kg/day) for three months. The establishment of DCM model and the effects of LMWF on cardiac function were evaluated by echocardiography and isolated heart perfusion. Ventricle staining with H-E or Sirius Red was performed to investigate the structural changes in myocardium. Functional evaluation demonstrated that LMWF has a beneficial effect on DCM by enhancing myocardial contractility and mitigating cardiac fibrosis. Additionally, LMWF exerted significant inhibitory effects on the reactive oxygen species production and myocyte apoptosis in diabetic hearts. The depressed activity of superoxide dismutase in diabetic heart was also improved by intervention with LMWF. Moreover, LMWF robustly inhibited the enhanced expression of protein kinase C β, an important contributor to oxidative stress, in diabetic heart and high glucose-treated cardiomyocytes. In conclusion, LMWF possesses a protective effect against DCM through ameliorations of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis in diabetes.
Effects of Zolpidem CR on Sleep and Nocturnal Ventilation in Patients with Heart Failure.
Gatti, Rodrigo C; Burke, Patrick R; Otuyama, Leonardo J; Almeida, Dirceu R; Tufik, Sergio; Poyares, Dalva
2016-08-01
This study aimed to evaluate the effects of zolpidem CR (controlled release) on sleep and nocturnal ventilation in patients with congestive heart failure, a population at risk for insomnia and poor sleep quality. Fifteen patients with heart failure (ischemic cardiomyopathy) and ejection fraction ≤ 45% in NYHA functional class I or II were evaluated with full polysomnography in a placebo-controlled, double-blind, randomized trial. Patients underwent three tests: (1) baseline polysomnography and, after randomization, (2) a new test with zolpidem CR 12.5 mg or placebo, and after 1 week, (3) a new polysomnography, crossing the "medication" used. A 16% increase in total sleep time was found with the use of zolpidem CR and an increase in stage 3 NREM sleep (slow wave sleep). The apnea hypopnea index (AHI) did not change with zolpidem CR even after controlling for supine position; however, a slight but significant decrease was observed in lowest oxygen saturation compared with baseline and placebo conditions (83.60 ± 5.51; 84.43 ± 3.80; 80.71 ± 5.18, P = 0.002). Zolpidem CR improved sleep structure in patients with heart failure, did not change apnea hypopnea index, but slightly decreased lowest oxygen saturation. © 2016 Associated Professional Sleep Societies, LLC.
Smith, A M; Sim, F H; Smith, H C; Stuart, M J; Laskowski, E R
1998-01-01
To determine the relationship between psychologic, situational, and physiologic variables and on-ice performance of youth hockey goalkeepers. This study was structured to identify relationships and predictors of goalie performance. Because athletes playing solo positions in team sports have not been analyzed in depth in terms of precompetition anxiety and because goalkeeper performance is critical to game outcome, we undertook a study of 43 goalies at a hockey camp. These goalies completed psychometric inventories to assess trait and state anxiety, confidence, life stress, and social support. Holter monitors measured heart rate while the goalies rotated through on-ice stations. Goalies were videotaped at the puck-shooting machine station, and performance (percent saves) was calculated. Trait (somatic) anxiety and positive mood state (ability to share) had different but significant relationships with on-ice performance. Heart rates ranged from 88 to 208 beats/min at the on-ice stations. Mean heart rate for older goalies (14 to 18 years of age) was 164 beats/min at the puck-shooting machine and 176 beats/min at other stations such as the slap-shot station. Older goalies performed well at a high level of arousal. Better performing goalies were more experienced, had faster heart rates "in the net," and had lower scores on all measures of anxiety.
Doherty, John U; Kort, Smadar; Mehran, Roxana; Schoenhagen, Paul; Soman, Prem; Dehmer, Greg J; Doherty, John U; Schoenhagen, Paul; Amin, Zahid; Bashore, Thomas M; Boyle, Andrew; Calnon, Dennis A; Carabello, Blase; Cerqueira, Manuel D; Conte, John; Desai, Milind; Edmundowicz, Daniel; Ferrari, Victor A; Ghoshhajra, Brian; Mehrotra, Praveen; Nazarian, Saman; Reece, T Brett; Tamarappoo, Balaji; Tzou, Wendy S; Wong, John B; Doherty, John U; Dehmer, Gregory J; Bailey, Steven R; Bhave, Nicole M; Brown, Alan S; Daugherty, Stacie L; Dean, Larry S; Desai, Milind Y; Duvernoy, Claire S; Gillam, Linda D; Hendel, Robert C; Kramer, Christopher M; Lindsay, Bruce D; Manning, Warren J; Mehrotra, Praveen; Patel, Manesh R; Sachdeva, Ritu; Wann, L Samuel; Winchester, David E; Wolk, Michael J; Allen, Joseph M
2018-04-01
This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities. Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines. A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario. The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will improve and standardize physician decision making. AUC publications reflect an ongoing effort by the American College of Cardiology to critically and systematically create, review, and categorize clinical situations where diagnostic tests and procedures are utilized by physicians caring for patients with cardiovascular diseases. The process is based on the current understanding of the technical capabilities of the imaging modalities examined. Copyright © 2017. Published by Elsevier Inc.
Doherty, John U; Kort, Smadar; Mehran, Roxana; Schoenhagen, Paul; Soman, Prem
2017-12-01
This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities.Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines.A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario.The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will improve and standardize physician decision making. AUC publications reflect an ongoing effort by the American College of Cardiology to critically and systematically create, review, and categorize clinical situations where diagnostic tests and procedures are utilized by physicians caring for patients with cardiovascular diseases. The process is based on the current understanding of the technical capabilities of the imaging modalities examined.
Zamanian, Zahra; Rostami, Reza; Hasanzadeh, Jafar; Hashemi, Hassan
2013-01-01
Background and Objectives. This study aimed to investigate the effect of noise exposure on blood pressure and heart rate of steel industry workers. Materials and Methods. In the present cross-sectional study, 50 workers were selected from a steel company in Fars province, Iran, and exposed to 85, 95, and 105 dB noise levels for 5 minutes. The participants' blood pressure and heart rate were measured using Beurer BC16 pulse meter both before and after the exposure. Results. The study results showed no significant difference in blood pressure and heart rate before and after the exposure. However, the workers' systolic blood pressure had increased compared to before the exposure; of course, the difference was not statistically significant (P > 0.05). Besides, although the subjects' heart rate had reduced in comparison to before the exposure, the difference was not statistically significant (P > 0.05). Conclusion. No significant change was observed in blood pressure and heart rate after acute exposure to 85, 95, and 105 dB noise levels. PMID:23781252
Kato, Yuko; Suzuki, Shinya; Uejima, Tokuhisa; Semba, Hiroaki; Nagayama, Osamu; Hayama, Etsuko; Arita, Takuto; Yagi, Naoharu; Kano, Hiroto; Matsuno, Shunsuke; Otsuka, Takayuki; Oikawa, Yuji; Kunihara, Takashi; Yajima, Junji; Yamashita, Takeshi
2018-05-01
Background Ventilatory efficiency decreases with age. This study aimed to investigate the prognostic significance and cut-off value of the minute ventilation/carbon dioxide production (VE/VCO 2 ) slope according to age in patients with heart failure. Methods and results We analysed 1501 patients with heart failure from our observational cohort who performed maximal symptom-limited cardiopulmonary exercise testing and separated them into three age groups (≤55 years, 56-70 years and ≥71 years) in total and according to the three ejection fraction categories defined by European Society of Cardiology guidelines. The endpoint was set as heart failure events, hospitalisation for heart failure or death from heart failure. The VE/VCO 2 slope increased with age. During the median follow-up period of 4 years, 141 heart failure (9%) events occurred. In total, univariate Cox analyses showed that the VE/VCO 2 slope (cont.) was significantly related to heart failure events, while on multivariate analysis, the prognostic significance of the VE/VCO 2 slope (cont.) was poor, accompanied by a significant interaction with age ( P < 0.0001). The cut-off value of the VE/VCO 2 slope increased with the increase in age in not only the total but also the sub-ejection fraction categories. Multivariate analyses with a stepwise method adjusted for estimated glomerular filtration rate, peak oxygen consumption, atrial fibrillation and brain natriuretic peptide, showed that the predictive value of the binary VE/VCO 2 slope separated by the cut-off value varied according to age. There was a tendency for the prognostic significance to increase with age irrespective of ejection fraction. Conclusion The prognostic significance and cut-off value of the VE/VCO 2 slope may increase with advancing age.
Role and Value of Clinical Pharmacy in Heart Failure Management.
Stough, W G; Patterson, J H
2017-08-01
Effectively managing heart failure requires a multidisciplinary, holistic approach attuned to many factors: diagnosis of structural and functional cardiac abnormalities; medication, device, or surgical management; concomitant treatment of comorbidities; physical rehabilitation; dietary considerations; and social factors. This practice paper highlights the pharmacist's role in the management of patients with heart failure, the evidence supporting their functions, and steps to ensure the pharmacist resource is available to the broad population of patients with heart failure. © 2017 American Society for Clinical Pharmacology and Therapeutics.
Chakravarthy, Murali; Sunilkumar, Gubbihalli; Pargaonkar, Sumant; Hosur, Rajathadri; Harivelam, Chidananda; Kavaraganahalli, Deepak; Srinivasan, Pradeep
2015-01-01
Objective: The purpose of our study was to determine the effect of induced apnea on quality of cardiopulmonary structures during computerized tomographic (CT) angiography images in children with congenital heart diseases. Methods: Pediatric patients with congenital heart defects undergoing cardiac CT angiography at our facility in the past 3 years participated in this study. The earlier patients underwent cardiac CT angiography without induced apnea and while, later, apnea was induced in patients, which was followed by electrocardiogram gated cardiac CT angiography. General anesthesia was induced using sleep dose of intravenous propofol. After the initial check CT, on request by the radiologist, apnea was induced by the anesthesiologist by administering 1 mg/kg of intravenous suxamethonium. Soon after apnea ensued, the contrast was injected, and CT angiogram carried out. CT images in the “apnea group” were compared with those in “nonapnea group.” After the completion of the procedure, the patients were mask ventilated with 100% oxygen till the spontaneous ventilation was restored. Results: We studied 46 patients, of whom 36 with apnea and yet another 10 without. The quality of the image, visualization of structures such as cardiac wall, outflow tracts, lung field, aortopulmonary shunts, and coronary arteries were analyzed and subjected to statistical analysis (Mann–Whitney U, Fischer's exact test and Pearson's Chi-square test). In the induced apnea group, overall image quality was considered excellent in 89% (n = 33) of the studies, while in the “no apnea group,” only 30% of studies were excellent. Absent or minimal motion artifacts were seen in a majority of the studies in apnea group (94%). In the nonapnea group, the respiratory and body motion artifacts were severe in 50%, moderate in 30%, and minimal in 20%, but they were significantly lesser in the apnea group. All the studied parameters were statistically significant in the apnea group in contrast to nonapnea group (P < 0.000). Conclusion: The image quality of cardiac CT angiography greatly improves, and motion artifact significantly decreases with the use of induced apnea in pediatrics patients being evaluated for congenital heart disease. This technique poses no additional morbidity of significance. PMID:25849686
[Respiratory infections, Down's syndrome and congenital heart disease: the CIVIC 21 study].
Medrano López, C; García-Guereta Silva, L; Lirio Casero, J; García Pérez, J
2009-07-01
We compare hospitalisation rates for acute respiratory tract infection in children younger than 24 months with significant congenital heart disease without Down's syndrome with those with Down's syndrome with or without congenital heart disease. This was an epidemiological, multicentre (53 Spanish hospitals), observational and prospective study, from October 2006 to April 2007. A total of 1085 patients were followed-up, of which 806 did not have Down's syndrome and 279 with Down's syndrome: 135 with significant, 38 with non significant and 105 without congenital heart disease. A total of 147 patients (13.1%; 95% CI, 11.2-15.2%) required hospitalisation due to respiratory infection. Rates in patients without and with Down's syndrome were 11% vs 19.1%. In the Down's group, 26.3% had no significant, a 23% had significant and 11.4% had no congenital heart disease. The main diagnosis was bronchiolitis (59.4%). An infectious agent was found in 36.2% cases. The specific admission rate due to respiratory syncytial virus was 4.4%, with differences in children without vs with Down's syndrome (3.2% vs 7.8%). In the Down's patients we found rates of 15.8%, 9.3% and 3% in the non-significant, significant and no congenital heart disease. Immunoprophylaxis against respiratory syncytial virus rates were 83.4% vs 39.9% in no Down's versus Down's syndrome patients. No differences were found in hospital stay or the severity. Hospital admission rates due to respiratory infection, and specifically respiratory syncytial virus, were higher in the Down's patients, particularly in the group with no significant congenital heart disease and low immunoprophylaxis against respiratory syncytial virus.
Maternal cardiac and obstetric performance in consecutive pregnancies in women with heart disease.
Gelson, E; Curry, R; Gatzoulis, M A; Swan, L; Lupton, M; Steer, P J; Johnson, M R
2015-10-01
Second pregnancies are usually less complicated than first pregnancies, and have a better outcome in terms of fetal growth. We studied a group of women with heart disease to assess whether their second pregnancy was less complicated and resulted in a larger baby. Retrospective case control study. Tertiary referral academic obstetric unit. First and second pregnancies in 77 women with congenital and acquired heart disease and in 154 control women were identified. Data were collected from medical and obstetric records. Cardiac complications, obstetric complications, intra-partum events, birthweight and perinatal complications. The rate of obstetric complication was greater in first pregnancies in both the heart disease and the control groups (38% versus 26%, cf. 20% versus 17%). In the heart disease group, the rate of cardiac complications was similar in first and second pregnancies (9% versus 6%). Overall, significantly more perinatal complications were seen in the heart disease group, with no significant difference between first and second pregnancies (36% versus 27%, cf. 14% versus 12%). Median birthweight was significantly higher in second pregnancies in the control group (3308 versus 3519 g P < 0.001), but not significantly different between pregnancies in the heart disease group (3014 versus 3133 g, P = 0.19). This case control study demonstrates that women with mild to moderate heart disease have similar pregnancy outcomes in consecutive pregnancies. However, while the median birthweight was higher in the control second pregnancies, it was not increased in the women with heart disease. A study of women with heart disease to assess whether their second pregnancy was less complicated. © 2015 Royal College of Obstetricians and Gynaecologists.
Paraoxonase 2 prevents the development of heart failure.
Li, Wei; Kennedy, David; Shao, Zhili; Wang, Xi; Kamdar, Andre Klaassen; Weber, Malory; Mislick, Kayla; Kiefer, Kathryn; Morales, Rommel; Agatisa-Boyle, Brendan; Shih, Diana M; Reddy, Srinivasa T; Moravec, Christine S; Tang, W H Wilson
2018-05-02
Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression. Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression. To determine the cardiac-specific function of PON2, we performed heart transplantations in which PON2-def and wild type (WT) donor hearts were implanted into WT recipient mice. Beating scores of the donor hearts, assessed at 4 weeks post-transplantation, were significantly decreased in PON2-def hearts when compared to WT donor hearts. By using a transverse aortic constriction (TAC) model, we found PON2 deficiency significantly exacerbated left ventricular remodeling and cardiac fibrosis post-TAC. We further demonstrated PON2 deficiency significantly enhanced ROS generation in heart tissues post-TAC. ROS generation was measured through dihydroethidium (DHE) using high-pressure liquid chromatography (HPLC) with a fluorescent detector. By using neonatal cardiomyocytes treated with CoCl 2 to mimic hypoxia, we found PON2 deficiency dramatically increased ROS generation in the cardiomyocytes upon CoCl 2 treatment. In response to a short CoCl 2 exposure, cell viability and succinate dehydrogenase (SDH) activity assessed by MTT assay were significantly diminished in PON2-def cardiomyocytes compared to those in WT cardiomyocytes. PON2-def cardiomyocytes also had lower baseline SDH activity. By using adult mouse cardiomyocytes and mitochondrial ToxGlo assay, we found impaired cellular ATP generation in PON2-def cells compared to that in WT cells, suggesting that PON2 is necessary for proper mitochondrial function. Our study suggests a cardioprotective role for PON2 in both experimental and human heart failure, which may be associated with the ability of PON2 to improve mitochondrial function and diminish ROS generation. Copyright © 2018 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Marino, Kady B.; Hoover-Miller, Anne; Conlon, Suzanne
This study quantified the Hg levels in the liver (n=98) and heart (n=43) tissues of Harbor Seals (Phoca vitulina) (n=102) harvested from Prince William Sound and Kodiak Island Alaska. Mercury tissue dry weight (dw) concentrations in the liver ranged from 1.7 to 393 ppm dw, and in the heart from 0.19 to 4.99 ppm dw. Results of this study indicate liver and heart tissues' Hg ppm dw concentrations significantly increase with age. Male Harbor Seals bioaccumulated Hg in both their liver and heart tissues at a significantly faster rate than females. The liver Hg bioaccumulation rates between the harvest locationsmore » Kodiak Island and Prince William Sound were not found to be significantly different. On adsorption Hg is transported throughout the Harbor Seal's body with the partition coefficient higher for the liver than the heart. No significant differences in the bio-distribution (liver:heart Hg ppm dw ratios (n=38)) values were found with respect to either age, sex or geographic harvest location. In this study the age at which Hg liver and heart bioaccumulation levels become significantly distinct in male and female Harbor Seals were identified through a Tukey's analysis. Of notably concern to human health was a male Harbor Seal's liver tissue harvested from Kodiak Island region. Mercury accumulation in this sample tissue was determined through a Q-test to be an outlier, having far higher Hg concentrarion (liver 392 Hg ppm dw) than the general population sampled. - Highlights: Black-Right-Pointing-Pointer Mercury accumulation in the liver and heart of seals exceed food safety guidelines. Black-Right-Pointing-Pointer Accumulation rate is greater in males than females with age. Black-Right-Pointing-Pointer Liver mercury accumulation is greater than in the heart tissues. Black-Right-Pointing-Pointer Mercury determination by USA EPA Method 7473 using thermal decomposition.« less
Hung, Ta-Chuan; Wang, Kuang-Te; Yun, Chun-Ho; Kuo, Jen-Yuan; Hou, Charles Jia-Yin; Liu, Chia-Yuan; Wu, Tung-Hsin; Bezerra, Hiram G; Cheng, Hsiao-Yang; Hung, Chung-Lieh; Yeh, Hung-I
2017-03-15
The relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac structural or functional anomalies in pre-clinical, asymptomatic Asian populations has not been well identified. From October 2005 to March 2008, we enrolled consecutive asymptomatic adults with preserved global left ventricular (LV) function (ejection fraction>50%) who underwent annual cardiovascular health survey. Circulating NT-proBNP was used to identify echo-defined cardiac structural/functional anomalies and compared to current recommended cut-off from the European Society of Heart Failure. Among 976 eligible subjects, 371 (38%) had structural heart diseases. Echocardiography-based left atrial diameter (Coef: 71.2), diastolic dysfunction (Coef: 35.4), and presence of pulmonary hypertension (Coef: 83.1) or valvular heart disease (Coef: 56.1, all p<0.05) of any form independently predicted circulating NT-ProBNP. NT-ProBNP cut-off values of 32.8 and 115.4pg/ml for subjects aged ≤ and >75years, respectively, demonstrated areas under the receiver operating characteristic curve of 0.76 (95% CI: 0.73-0.80) and 0.70 (95% CI: 0.52-0.88) for predicting structural or functional anomaly. We examined the feasibility of NT-ProBNP for identifying cardiac structural and functional anomaly in an asymptomatic ethnic Taiwanese population with a relatively lower cut-off value, indicating its potential role for pre-clinical screening of Asian patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Luo, Y; Liao, Z; Jiang, W
Purpose: To evaluate the feasibility of using an automatic segmentation tool to delineate cardiac substructures from computed tomography (CT) images for cardiac toxicity analysis for non-small cell lung cancer (NSCLC) patients after radiotherapy. Methods: A multi-atlas segmentation tool developed in-house was used to delineate eleven cardiac substructures including the whole heart, four heart chambers, and six greater vessels automatically from the averaged 4DCT planning images for 49 NSCLC patients. The automatic segmented contours were edited appropriately by two experienced radiation oncologists. The modified contours were compared with the auto-segmented contours using Dice similarity coefficient (DSC) and mean surface distance (MSD)more » to evaluate how much modification was needed. In addition, the dose volume histogram (DVH) of the modified contours were compared with that of the auto-segmented contours to evaluate the dosimetric difference between modified and auto-segmented contours. Results: Of the eleven structures, the averaged DSC values ranged from 0.73 ± 0.08 to 0.95 ± 0.04 and the averaged MSD values ranged from 1.3 ± 0.6 mm to 2.9 ± 5.1mm for the 49 patients. Overall, the modification is small. The pulmonary vein (PV) and the inferior vena cava required the most modifications. The V30 (volume receiving 30 Gy or above) for the whole heart and the mean dose to the whole heart and four heart chambers did not show statistically significant difference between modified and auto-segmented contours. The maximum dose to the greater vessels did not show statistically significant difference except for the PV. Conclusion: The automatic segmentation of the cardiac substructures did not require substantial modification. The dosimetric evaluation showed no statistically significant difference between auto-segmented and modified contours except for the PV, which suggests that auto-segmented contours for the cardiac dose response study are feasible in the clinical practice with a minor modification to the PV vessel.« less
Rasheed, Abdullah; Jabbour, Salma K; Rosenberg, Stephen; Patel, Ajay; Goyal, Sharad; Haffty, Bruce G; Yue, Ning J; Khan, Alvin
2016-01-01
Lung tumors move during respiration, complicating radiation therapy. The abdominal compression plate (ACP) is thought to reduce respiratory motion. This study quantifies ACP efficacy on respiratory-induced motion by using 4-dimensional computed tomography to evaluate volume and displacement changes of the heart, lungs, and tumor with and without ACP. Lung cancer patients (n = 17) received 4-dimensional computed tomography simulations (10 computed tomography scans from 0% to 90% breathing phases) with and without ACP under maximally tolerated diaphragmatic pressure. Gross tumor volume (GTV), heart, and lungs were contoured in treatment planning software for each phase. Structures were exported for analysis. For each phase, with and without ACP, tumor and organ absolute centroid range of motion and volume were calculated. ACP did not significantly affect GTV, heart, or lung motion on the sample as a whole, but instead demonstrated patient-specific results. ACP reduced GTV motion in 3 (17.6%; 3 upper lobe tumors) by 2.9 mm (P < .01), increased motion in 5 (29.4%; 3 upper lobe tumors, 1 middle lobe, 1 lower lobe) by 1.9 mm (P < .03), and did not significantly change 9. Of the 3 patients exhibiting significantly decreased GTV motion, GTV, heart, and lung range of motion was 7.4 mm, 11.8 mm, and 11.9 mm, respectively, without compression and 4.5 mm, 8.4 mm, and 10.9 mm, respectively, with compression. Averaged across the sample, ACP did not exhibit any axis-specific effect. ACP efficacy was patient-specific, possibly because of pre-existing factors including chronic obstructive pulmonary disease severity, chest wall elasticity, tumor location, and patient comfort. Tumor lobe location does not predetermine compression efficacy; therefore, patients should be simulated with and without ACP, regardless of tumor location. GTV motion seems most important in determining suitability for compression. Alternative motion control should be considered in patients not benefited by compression. In patients who benefited, ACP may enhance tumor coverage while minimizing toxicity. Larger scale studies are necessary for definitive treatment recommendations. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Effects of Zolpidem CR on Sleep and Nocturnal Ventilation in Patients with Heart Failure
Gatti, Rodrigo C.; Burke, Patrick R.; Otuyama, Leonardo J.; Almeida, Dirceu R.; Tufik, Sergio; Poyares, Dalva
2016-01-01
Study Objective: This study aimed to evaluate the effects of zolpidem CR (controlled release) on sleep and nocturnal ventilation in patients with congestive heart failure, a population at risk for insomnia and poor sleep quality. Methods: Fifteen patients with heart failure (ischemic cardiomyopathy) and ejection fraction ≤ 45% in NYHA functional class I or II were evaluated with full polysomnography in a placebo-controlled, double-blind, randomized trial. Patients underwent three tests: (1) baseline polysomnography and, after randomization, (2) a new test with zolpidem CR 12.5 mg or placebo, and after 1 week, (3) a new polysomnography, crossing the “medication” used. Results: A 16% increase in total sleep time was found with the use of zolpidem CR and an increase in stage 3 NREM sleep (slow wave sleep). The apnea hypopnea index (AHI) did not change with zolpidem CR even after controlling for supine position; however, a slight but significant decrease was observed in lowest oxygen saturation compared with baseline and placebo conditions (83.60 ± 5.51; 84.43 ± 3.80; 80.71 ± 5.18, P = 0.002). Conclusion: Zolpidem CR improved sleep structure in patients with heart failure, did not change apnea hypopnea index, but slightly decreased lowest oxygen saturation. Citation: Gatti RC, Burke PR, Otuyama LJ, Almeida DR, Tufik S, Poyares D. Effects of zolpidem CR on sleep and nocturnal ventilation in patients with heart failure. SLEEP 2016;39(8):1501–1505. PMID:27166233
Bello, Natalie A; Cheng, Susan; Claggett, Brian; Shah, Amil M; Ndumele, Chiadi E; Roca, Gabriela Querejeta; Santos, Angela B S; Gupta, Deepak; Vardeny, Orly; Aguilar, David; Folsom, Aaron R; Butler, Kenneth R; Kitzman, Dalane W; Coresh, Josef; Solomon, Scott D
2016-08-01
Obesity increases cardiovascular risk. However, the extent to which various measures of body composition are associated with abnormalities in cardiac structure and function, independent of comorbidities commonly affecting obese individuals, is not clear. This study sought to examine the relationship between body mass index, waist circumference, and percent body fat with conventional and advanced measures of cardiac structure and function. We studied 4343 participants of the ARIC study (Atherosclerosis Risk in Communities) who were aged 69 to 82 years, free of coronary heart disease and heart failure, and underwent comprehensive echocardiography. Increasing body mass index, waist circumference, and body fat were associated with greater left ventricular (LV) mass and left atrial volume indexed to height(2.7) in both men and women (P<0.001). In women, all 3 measures were associated with abnormal LV geometry, and increasing waist circumference and body fat were associated with worse global longitudinal strain, a measure of LV systolic function. In both sexes, increasing body mass index was associated with greater right ventricular end-diastolic area and worse right ventricular fractional area change (P≤0.001). We observed similar associations for both waist circumference and percent body fat. In a large, biracial cohort of older adults free of clinically overt coronary heart disease or heart failure, obesity was associated with subclinical abnormalities in cardiac structure in both men and women and with adverse LV remodeling and impaired LV systolic function in women. These data highlight the association of obesity and subclinical abnormalities of cardiac structure and function, particularly in women. © 2016 American Heart Association, Inc.
Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.
Frisk, Michael; Ruud, Marianne; Espe, Emil K S; Aronsen, Jan Magnus; Røe, Åsmund T; Zhang, Lili; Norseng, Per Andreas; Sejersted, Ole M; Christensen, Geir A; Sjaastad, Ivar; Louch, William E
2016-10-01
Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation-contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca(2+) release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function. MRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca(2+) release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss. Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca(2+) release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.
Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion.
Maity, Sangeeta; Kar, Dipak; De, Kakali; Chander, Vivek; Bandyopadhyay, Arun
2013-05-01
This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.
Three-dimensional cardiac architecture determined by two-photon microtomy
NASA Astrophysics Data System (ADS)
Huang, Hayden; MacGillivray, Catherine; Kwon, Hyuk-Sang; Lammerding, Jan; Robbins, Jeffrey; Lee, Richard T.; So, Peter
2009-07-01
Cardiac architecture is inherently three-dimensional, yet most characterizations rely on two-dimensional histological slices or dissociated cells, which remove the native geometry of the heart. We previously developed a method for labeling intact heart sections without dissociation and imaging large volumes while preserving their three-dimensional structure. We further refine this method to permit quantitative analysis of imaged sections. After data acquisition, these sections are assembled using image-processing tools, and qualitative and quantitative information is extracted. By examining the reconstructed cardiac blocks, one can observe end-to-end adjacent cardiac myocytes (cardiac strands) changing cross-sectional geometries, merging and separating from other strands. Quantitatively, representative cross-sectional areas typically used for determining hypertrophy omit the three-dimensional component; we show that taking orientation into account can significantly alter the analysis. Using fast-Fourier transform analysis, we analyze the gross organization of cardiac strands in three dimensions. By characterizing cardiac structure in three dimensions, we are able to determine that the α crystallin mutation leads to hypertrophy with cross-sectional area increases, but not necessarily via changes in fiber orientation distribution.
Wan, Ruiqian; Ahmet, Ismayil; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Talan, Mark; Mattson, Mark P.
2009-01-01
It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats. Echocardiographic analysis of heart structural and functional variables revealed that IF attenuates the growth-related increase in posterior ventricular wall thickness, , end systolic and diastolic volumes, and reduces the ejection fraction. The size of the ischemic infarct 24 hours following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after myocardial infarction. Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF. PMID:19423320
Siegrist, Johannes; Li, Jian
2017-11-10
While epidemiological studies provide statistical evidence on associations of exposures such as stressful work with elevated risks of stress-related disorders (e.g., coronary heart disease or depression), additional information on biological pathways and biomarkers underlying these associations is required. In this contribution, we summarize the current state of the art on research findings linking stressful work, in terms of an established theoretical model-effort-reward imbalance-with a broad range of biomarkers. Based on structured electronic literature search and recent available systematic reviews, our synthesis of findings indicates that associations of work stress with heart rate variability, altered blood lipids, and risk of metabolic syndrome are rather consistent and robust. Significant relationships with blood pressure, heart rate, altered immune function and inflammation, cortisol release, and haemostatic biomarkers were also observed, but due to conflicting findings additional data will be needed to reach a firm conclusion. This narrative review of empirical evidence supports the argument that the biomarkers under study can act as mediators of epidemiologically established associations of work stress, as measured by effort-reward imbalance, with incident stress-related disorders.
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.
Kampourakis, Thomas; Sun, Yin-Biao; Irving, Malcolm
2016-01-01
Contraction of heart muscle is triggered by calcium binding to the actin-containing thin filaments but modulated by structural changes in the myosin-containing thick filaments. We used phosphorylation of the myosin regulatory light chain (cRLC) by the cardiac isoform of its specific kinase to elucidate mechanisms of thick filament-mediated contractile regulation in demembranated trabeculae from the rat right ventricle. cRLC phosphorylation enhanced active force and its calcium sensitivity and altered thick filament structure as reported by bifunctional rhodamine probes on the cRLC: the myosin head domains became more perpendicular to the filament axis. The effects of cRLC phosphorylation on thick filament structure and its calcium sensitivity were mimicked by increasing sarcomere length or by deleting the N terminus of the cRLC. Changes in thick filament structure were highly cooperative with respect to either calcium concentration or extent of cRLC phosphorylation. Probes on unphosphorylated myosin heads reported similar structural changes when neighboring heads were phosphorylated, directly demonstrating signaling between myosin heads. Moreover probes on troponin showed that calcium sensitization by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thick and thin filaments that is still present when active force is blocked by Blebbistatin. These results show that coordinated and cooperative structural changes in the thick and thin filaments are fundamental to the physiological regulation of contractility in the heart. This integrated dual-filament concept of contractile regulation may aid understanding of functional effects of mutations in the protein components of both filaments associated with heart disease. PMID:27162358
Kampourakis, Thomas; Sun, Yin-Biao; Irving, Malcolm
2016-05-24
Contraction of heart muscle is triggered by calcium binding to the actin-containing thin filaments but modulated by structural changes in the myosin-containing thick filaments. We used phosphorylation of the myosin regulatory light chain (cRLC) by the cardiac isoform of its specific kinase to elucidate mechanisms of thick filament-mediated contractile regulation in demembranated trabeculae from the rat right ventricle. cRLC phosphorylation enhanced active force and its calcium sensitivity and altered thick filament structure as reported by bifunctional rhodamine probes on the cRLC: the myosin head domains became more perpendicular to the filament axis. The effects of cRLC phosphorylation on thick filament structure and its calcium sensitivity were mimicked by increasing sarcomere length or by deleting the N terminus of the cRLC. Changes in thick filament structure were highly cooperative with respect to either calcium concentration or extent of cRLC phosphorylation. Probes on unphosphorylated myosin heads reported similar structural changes when neighboring heads were phosphorylated, directly demonstrating signaling between myosin heads. Moreover probes on troponin showed that calcium sensitization by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thick and thin filaments that is still present when active force is blocked by Blebbistatin. These results show that coordinated and cooperative structural changes in the thick and thin filaments are fundamental to the physiological regulation of contractility in the heart. This integrated dual-filament concept of contractile regulation may aid understanding of functional effects of mutations in the protein components of both filaments associated with heart disease.
Allopurinol improves endothelial dysfunction in chronic heart failure.
Farquharson, Colin A J; Butler, Robert; Hill, Alexander; Belch, Jill J F; Struthers, Allan D
2002-07-09
Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure. We performed a randomized, placebo-controlled, double-blind crossover study on 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean+/-SEM]: 181+/-19% versus 120+/-22% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346+/-128 nmol/L versus 461+/-101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy. We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.
Grigg, G C; Seebacher, F
1999-01-01
The discovery that changes in heart rate and blood flow allow some reptiles to heat faster than they cool has become a central paradigm in our understanding of reptilian thermoregulation. However, this hysteresis in heart rate has been demonstrated only in simplistic laboratory heating and cooling trials, leaving its functional significance in free-ranging animals unproven. To test the validity of this paradigm, we measured heart rate and body temperature (Tb) in undisturbed, free-ranging bearded dragons (Pogona barbata), the species in which this phenomenon was first described. Our field data confirmed the paradigm and we found that heart rate during heating usually exceeded heart rate during cooling at any Tb. Importantly, however, we discovered that heart rate was proportionally faster in cool lizards whose Tb was still well below the 'preferred Tb range' compared to lizards whose Tb was already close to it. Similarly, heart rate during cooling was proportionally slower the warmer the lizard and the greater its cooling potential compared to lizards whose Tb was already near minimum operative temperature. Further, we predicted that, if heart rate hysteresis has functional significance, a 'reverse hysteresis' pattern should be observable when lizards risked overheating. This was indeed the case and, during heating on those occasions when Tb reached very high levels (> 40 degrees C), heart rate was significantly lower than heart rate during the immediately following cooling phase. These results demonstrate that physiological control of thermoregulation in reptiles is more complex than has been previously recognized. PMID:10418165
Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy
Ames, EG; Lawson, MJ; Mackey, AJ; Holmes, JW
2013-01-01
Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are reexpressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing of mRNA transcripts has been shown to be temporally regulated during heart development, leading us to consider whether fetal patterns of splicing also reappear during hypertrophy. We hypothesized that patterns of alternative splicing occurring during heart development are recapitulated during cardiac hypertrophy. Here we present a study of isoform expression during pressure-overload cardiac hypertrophy induced by 10 days of transverse aortic constriction (TAC) in rats and in developing fetal rat hearts compared to sham-operated adult rat hearts, using high-throughput sequencing of poly(A) tail mRNA. We find a striking degree of overlap between the isoforms expressed differentially in fetal and pressure-overloaded hearts compared to control: forty-four percent of the isoforms with significantly altered expression in TAC hearts are also expressed at significantly different levels in fetal hearts compared to control (P < 0.001). The isoforms that are shared between hypertrophy and fetal heart development are significantly enriched for genes involved in cytoskeletal organization, RNA processing, developmental processes, and metabolic enzymes. Our data strongly support the concept that mRNA splicing patterns normally associated with heart development recur as part of the hypertrophic response to pressure overload. These findings suggest that cardiac hypertrophy shares post-transcriptional as well as transcriptional regulatory mechanisms with fetal heart development. PMID:23688780
A Randomized Prospective Study Of The Use Of Ipads In Reducing Anxiety During Cast Room Procedures
Ko, Justine S.; Whiting, Zachariah; Nguyen, Cynthia; Liu, Raymond W; Gilmore, Allison
2016-01-01
Background Cast room procedures can be a source of anxiety for children. Various techniques, including music therapy, have been evaluated as a way to ease this anxiety. The use of iPads as a form of distraction during cast room procedures has not previously been evaluated and was the purpose of the current study. Methods 146 children and adolescents who underwent cast room procedures during June- August 2015 were randomly assigned to one of three groups: no-iPad, iPad with video, or iPad with game. Patient heart rates were measured using a pulse oximeter in the waiting room, before the procedure, during the procedure, and after the procedure. Mean values for each group were calculated at each time interval and compared both between groups and within groups over time. Results There were no significant differences in baseline (waiting room) heart rate between the no-iPad and iPad groups. When compared with the no-iPad group, there was a trend toward decreased heart rate in the video group (p=0.13) and a significant increase in heart rate in the game group (p=0.026) before the procedure. There were no significant decreases in heart rate within any of the groups when comparing the waiting room heart rates with the during procedure heart rates. There was a significant difference between the no-iPad and video groups (p=0.047) when comparing the change in heart rate from baseline to before the procedure, with a decreased heart rate observed in the video group. Conclusions The results of this study show a significant decrease in heart rate when transitioning from the waiting room to the cast room while watching videos on the iPad. iPad-based video delivery appears to decrease anxiety prior to cast room procedures. iPad-based game play is difficult to assess as elevations in heart rate prior to the procedure are presumed to be related to game play and confound the observed effect it may have on anxiety related to the procedure. PMID:27528849
Yip, G W; Ho, P P; Woo, K S; Sanderson, J E
1999-09-01
There is a wide variation (13% to 74%) in the reported prevalence of heart failure associated with normal left ventricular (LV) systolic function (diastolic heart failure). There is no published information on this condition in China. To ascertain the prevalence of diastolic heart failure in this community, 200 consecutive patients with the typical features of congestive heart failure were studied with standard 2-dimensional Doppler echocardiography. A LV ejection fraction (LVEF) >45% was considered normal. The results showed that 12.5% had significant valvular heart disease. Of the remaining 175 patients, 132 had a LVEF >45% (75%). Therefore, 66% of patients with a clinical diagnosis of heart failure had a normal LVEF. Heart failure with normal LV systolic function was more common than systolic heart failure in those >70 years old (65% vs 47%; p = 0.015). Most (57%) had an abnormal relaxation pattern in diastole and 14% had a restrictive filling pattern. In the systolic heart failure group, a restrictive filling pattern was more common (46%). There were no significant differences in the sex distribution, etiology, or prevalence of LV hypertrophy between these 2 heart failure groups. In conclusion, heart failure with a normal LVEF or diastolic heart failure is more common than systolic heart failure in Chinese patients with the symptoms of heart failure. This may be related to older age at presentation and the high prevalence of hypertension in this community.
Nocerino, Elisabetta; Mason, Peter J.; Schwahn, Denise J.; Hetzel, Scott; Turnquist, Alyssa M.; Lee, Fred T.; Brace, Christopher L.
2017-01-01
Purpose To determine how close to the heart pulmonary microwave ablation can be performed without causing cardiac tissue injury or significant arrhythmia. Materials and Methods The study was performed with approval from the institutional animal care and use committee. Computed tomographic fluoroscopically guided microwave ablation of the lung was performed in 12 swine. Antennas were randomized to either parallel (180° ± 20°) or perpendicular (90° ± 20°) orientation relative to the heart surface and to distances of 0–10 mm from the heart. Ablations were performed at 65 W for 5 minutes or until a significant arrhythmia (asystole, heart block, bradycardia, supraventricular or ventricular tachycardia) developed. Heart tissue was evaluated with vital staining and histologic examination. Data were analyzed with mixed effects logistic regression, receiver operating characteristic curves, and the Fisher exact test. Results Thirty-four pulmonary microwave ablations were performed with the antenna a median distance of 4 mm from the heart in both perpendicular (n = 17) and parallel (n = 17) orientation. Significant arrhythmias developed during six (18%) ablations. Cardiac tissue injury occurred with 17 ablations (50%). Risk of arrhythmia and tissue injury decreased with increasing antenna distance from the heart with both antenna orientations. No cardiac complication occurred with a distance of greater than or equal to 4.4 mm from the heart. The ablation zone extended to the pleural surface adjacent to the heart in 71% of parallel and 17% of perpendicular ablations performed 5–10 mm from the heart. Conclusion Microwave lung ablations performed more than or equal to 5 mm from the heart were associated with a low risk of cardiac complications. © RSNA, 2016 PMID:27732159
Heart transplant outcomes in recipients of Centers for Disease Control (CDC) high risk donors.
Tsiouris, Athanasios; Wilson, Lynn; Sekar, Rajesh B; Mangi, Abeel A; Yun, James J
2016-12-01
A lack of donor hearts remains a major limitation of heart transplantation. Hearts from Centers for Disease Control (CDC) high-risk donors can be utilized with specific recipient consent. However, outcomes of heart transplantation with CDC high-risk donors are not well known. We sought to define outcomes, including posttransplant hepatitis and human immunodeficiency virus (HIV) status, in recipients of CDC high-risk donor hearts at our institution. All heart transplant recipients from August 2010 to December 2014 (n = 74) were reviewed. Comparison of 1) CDC high-risk donor (HRD) versus 2) standard-risk donor (SRD) groups were performed using chi-squared tests for nominal data and Wilcoxon two-sample tests for continuous variables. Survival was estimated with Kaplan-Meier curves. Of 74 heart transplant recipients reviewed, 66 (89%) received a SRD heart and eight (11%) received a CDC HRD heart. We found no significant differences in recipient age, sex, waiting list 1A status, pretransplant left ventricular assist device (LVAD) support, cytomegalovirus (CMV) status, and graft ischemia times (p = NS) between the HRD and SRD groups. All of the eight HRD were seronegative at the time of transplant. Postoperatively, there was no significant difference in rejection rates at six and 12 months posttransplant. Importantly, no HRD recipients acquired hepatitis or HIV. Survival in HRD versus SRD recipients was not significantly different by Kaplan-Meier analysis (log rank p = 0.644) at five years posttransplant. Heart transplants that were seronegative at the time of transplant had similar posttransplant graft function, rejection rates, and five-year posttransplant survival versus recipients of SRD hearts. At our institution, no cases of hepatitis or HIV occurred in HRD recipients in early follow-up. © 2016 Wiley Periodicals, Inc.
Beckers, Paul J; Possemiers, Nadine M; Van Craenenbroeck, Emeline M; Van Berendoncks, An M; Wuyts, Kurt; Vrints, Christiaan J; Conraads, Viviane M
2012-02-01
Exercise training efficiently improves peak oxygen uptake (V˙O2peak) in patients with chronic heart failure. To optimize training-derived benefit, higher exercise intensities are being explored. The correct identification of anaerobic threshold is important to allow safe and effective exercise prescription. During 48 cardiopulmonary exercise tests obtained in patients with chronic heart failure (59.6 ± 11 yrs; left ventricular ejection fraction, 27.9% ± 9%), ventilatory gas analysis findings and lactate measurements were collected. Three technicians independently determined the respiratory compensation point (RCP), the heart rate turning point (HRTP) and the second lactate turning point (LTP2). Thereafter, exercise intensity (target heart rate and workload) was calculated and compared between the three methods applied. Patients had significantly reduced maximal exercise capacity (68% ± 21% of predicted V˙O2peak) and chronotropic incompetence (74% ± 7% of predicted peak heart rate). Heart rate, workload, and V˙O2 at HRTP and at RCP were not different, but at LTP2, these parameters were significantly (P < 0.0001) higher. Mean target heart rate and target workload calculated using the LTP2 were 5% and 12% higher compared with those calculated using HRTP and RCP, respectively. The calculation of target heart rate based on LTP2 was 5% and 10% higher in 12 of 48 (25%) and 6 of 48 (12.5%) patients, respectively, compared with the other two methods. In patients with chronic heart failure, RCP and HRTP, determined during cardiopulmonary exercise tests, precede the occurrence of LTP2. Target heart rates and workloads used to prescribe tailored exercise training in patients with chronic heart failure based on LTP2 are significantly higher than those derived from HRTP and RCP.
Nagel, Deborah; Gehlen, Heidrun
2013-01-01
The aim of this study was to evaluate to what extent the myocardial function in horses (measured by PW-tissue Doppler = PW-TDI) is affected during a sedation with romifidine (0.04 mg/kg, i. v.), particularly in case of an accompanying heart disease. Based on an echo- and electrocardiographic examination, a total of 45 horses was subdivided into group 1 (no heart disease), group 2 (heart disease without increased heart dimensions) and group 3 (heart disease with increased heart dimensions). Heart rate (HF), M-mode- (FS%) and TDI-measurements were performed before and after the application of romifidine. The velocities of the radial myocardial movement in the left and right ventricular wall were evaluated using PW-TDI. The TDI parameters included the isovolumic contraction (IVC), the systolic (S) as well as the early (E) and late diastolic maximal velocity (A). After the application of romifidine HF and FS were significantly decreased in all groups. IVC, S and E, determined by PW-TDI were also significantly decreased in both ventricular walls. A significant difference between groups was shown for the isovolumic contraction in the left ventricular wall. This was observed distinctly more in horses with heart disease and increased heart dimensions compared to horses with heart disease but no increased heart dimensions. The results of the study indicate that PW-TDI is a suitable imaging technique to analyse the effects of romifidine on equine myocardial function. The major percentage change after application of romifidine for TDI measurements compared to the M-mode parameters indicate that the parameter myocardial velocity measured with TDI appeared to be the most sensitive parameter to document romifidine--induced changes on the myocardium.
Comparing fist size to heart size is not a viable technique to assess cardiomegaly.
Ampanozi, Garyfalia; Krinke, Eileen; Laberke, Patrick; Schweitzer, Wolf; Thali, Michael J; Ebert, Lars C
2018-05-07
Several medical textbooks state that a human heart is approximately the size of that person's fist. Stating that a heart has the size of the corpse's fist is thought to signify that the heart size is normal. We formulate two hypotheses that are tested in this article. First, we hypothesize that in cases without cardiomegaly, volumes of the hand and the heart are not significantly different. Second, we hypothesize that in cases of cardiomegaly, the heart volume statistically significantly exceeds that of the hand. We retrospectively reviewed 130 consecutive postmortem computed tomography datasets from the BLINDED starting from 01/01/2013, covering a period of approximately 3 months. Hands and hearts were segmented and their volumes estimated. We obtained the following information from the postmortem examination reports: age, sex, body length and weight, heart weight, cardiomegaly, and cause of death. When exploring the correlation between mean hand volume and heart volume, only in the group of the females with cardiomegaly (N=8) could a positive, statistically significant correlation be ascertained (Pearson correlation coefficient 0.753, P=.031). In this study, we demonstrated that the commonly used idea that a heart larger than the fist of a patient suggests cardiomegaly might be incorrect. Because this perception is commonly used in autopsy reports, it might lead to avoidable errors. Until further studies confirm this hypothesis, this informal measurement should no longer be taught or used. Copyright © 2018 Elsevier Inc. All rights reserved.
Korean immigrants' knowledge of heart attack symptoms and risk factors.
Hwang, Seon Y; Ryan, Catherine J; Zerwic, Julie Johnson
2008-02-01
This study assessed the knowledge of heart attack symptoms and risk factors in a convenience sample of Korean immigrants. A total of 116 Korean immigrants in a Midwestern metropolitan area were recruited through Korean churches and markets. Knowledge was assessed using both open-ended questions and a structured questionnaire. Latent class cluster analysis and Chi-square tests were used to analyze the data. About 76% of the sample had at least one self-reported risk factor for cardiovascular disease. Using an open-ended question, the majority of subjects could only identify one symptom. In the structured questionnaire, subjects identified a mean of 5 out of 10 heart attack symptoms and a mean of 5 out of 9 heart attack risk factors. Latent class cluster analysis showed that subjects clustered into two groups for both risk factors and symptoms: a high knowledge group and a low knowledge group. Subjects who clustered into the risk factor low knowledge group (48%) were more likely than the risk factor high knowledge group to be older than 65 years, to have lower education, to not know to use 911 when a heart attack occurred, and to not have a family history of heart attack. Korean immigrants' knowledge of heart attack symptoms and risk factors was variable, ranging from high to very low. Education should be focused on those at highest risk for a heart attack, which includes the elderly and those with risk factors.
Ahn, Song Vogue; Kim, Hyeon Chang; Nam, Chung Mo; Suh, Il
2018-02-01
Diabetic women have a greater relative risk of coronary heart disease than diabetic men. However, the sex difference in the effect of fasting serum glucose levels below the diabetic range on the risk of coronary heart disease is unclear. We investigated whether the association between nondiabetic blood glucose levels and the incident risk of coronary heart disease is different between men and women. The fasting serum glucose levels and other cardiovascular risk factors at baseline were measured in 159,702 subjects (100,144 men and 59,558 women). Primary outcomes were hospital admission and death due to coronary heart disease during the 11-year follow-up. The risk for coronary heart disease in women significantly increased with impaired fasting glucose levels (≥110mg/dL) compared to normal glucose levels (<100mg/dL), whereas the risk for coronary heart disease in men was significantly increased at a diabetic glucose range (≥126mg/dL). Women had a higher hazard ratio of coronary heart disease associated with the fasting serum glucose level than men (p for interaction with sex=0.021). The stronger effect of the fasting serum glucose levels on the risk of coronary heart disease in women than in men was significant from a prediabetic range (≥110mg/dL). Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Zhang, Haining; Min, Dongyu; Fu, Mingyu; Tian, Jing; Wang, Qingwen; An, Xinjiang
2014-09-01
To explore the effects of astragalus (AST) , total flavone of astragalus (TFA), total saponins of astragalus (TSA) and astragalus polysaccharides (APS) on ischemia/reperfusion (40 min/60 min) injury in isolated guinea-pig heart. Isolated guinea-pig hearts underwent ischemia, then followed by K-H perfusion (I/R group), AST (60 mg/L),AST (60 mg/L), TFA (60 mg/L), TSA (60 mg/L) and APS (60 mg/L) perfusion (n = 6 each).Isolated hearts without ischemia serve as control group (n = 6). Activity of lactate dehydrogenas (LDH) and creatine kinase (CK) in effluent were measured.Infarct size, myocardial superoxide dismutase (SOD) activity and malondiadehyde (MDA) contents were also determined. Compared to control hearts, heart rate, coronary flow and myocardial superoxide dismutase (SOD) activity were significantly reduced, while LDH and CK in effluent as well as myocardial MDA were significantly increased in the I/R hearts during reperfusion (all P < 0.05), these changes could be partly reversed by AST and TFA perfusion.Infarct size was also significantly reduced in AST (11.9 ± 2.03) % and TFA (13.31 ± 1.17) % treated hearts compared to that in I/R group (18.9 ± 2.27) % (all P < 0.01). The findings indicate that AST and TFA could attenuate I/R injury in isolated guinea-pig heart possibly through enhancing the activity of SOD and reducing lipid peroxidation.
Non-Dimensional Formulation of Ventricular Work-Load Severity Under Concomitant Heart Valve Disease
NASA Astrophysics Data System (ADS)
Dong, Melody; Simon-Walker, Rachael; Dasi, Lakshmi
2012-11-01
Current guidelines on assessing the severity of heart valve disease rely on dimensional disease specific measures and are thus unable to capture severity under a concomitant heart valve disease scenario. Experiments were conducted to measure ventricular work-load in an in-house in-vitro left heart simulator. In-house tri-leaflet heart valves were built and parameterized to model concomitant heart valve disease. Measured ventricular power varied non-linearly with cardiac output and mean aortic pressure. Significant data collapse could be achieved by the non-dimensionalization of ventricular power with cardiac output, fluid density, and a length scale. The dimensionless power, Circulation Energy Dissipation Index (CEDI), indicates that concomitant conditions require a significant increase in the amount of work needed to sustain cardiac function. It predicts severity without the need to quantify individual disease severities. This indicates the need for new fluid-dynamics similitude based clinical guidelines to assist patients with multiple heart valve diseases. Funded by the American Heart Association.
The Failing Heart Relies on Ketone Bodies as a Fuel.
Aubert, Gregory; Martin, Ola J; Horton, Julie L; Lai, Ling; Vega, Rick B; Leone, Teresa C; Koves, Timothy; Gardell, Stephen J; Krüger, Marcus; Hoppel, Charles L; Lewandowski, E Douglas; Crawford, Peter A; Muoio, Deborah M; Kelly, Daniel P
2016-02-23
Significant evidence indicates that the failing heart is energy starved. During the development of heart failure, the capacity of the heart to utilize fatty acids, the chief fuel, is diminished. Identification of alternate pathways for myocardial fuel oxidation could unveil novel strategies to treat heart failure. Quantitative mitochondrial proteomics was used to identify energy metabolic derangements that occur during the development of cardiac hypertrophy and heart failure in well-defined mouse models. As expected, the amounts of proteins involved in fatty acid utilization were downregulated in myocardial samples from the failing heart. Conversely, expression of β-hydroxybutyrate dehydrogenase 1, a key enzyme in the ketone oxidation pathway, was increased in the heart failure samples. Studies of relative oxidation in an isolated heart preparation using ex vivo nuclear magnetic resonance combined with targeted quantitative myocardial metabolomic profiling using mass spectrometry revealed that the hypertrophied and failing heart shifts to oxidizing ketone bodies as a fuel source in the context of reduced capacity to oxidize fatty acids. Distinct myocardial metabolomic signatures of ketone oxidation were identified. These results indicate that the hypertrophied and failing heart shifts to ketone bodies as a significant fuel source for oxidative ATP production. Specific metabolite biosignatures of in vivo cardiac ketone utilization were identified. Future studies aimed at determining whether this fuel shift is adaptive or maladaptive could unveil new therapeutic strategies for heart failure. © 2016 American Heart Association, Inc.
Theodoridis, Karolina; Müller, Janina; Ramm, Robert; Findeisen, Katja; Andrée, Birgit; Korossis, Sotirios; Haverich, Axel; Hilfiker, Andres
2016-10-01
Non-fixed, decellularized allogeneic heart valve scaffolds seem to be the best choice for heart valve replacement, their availability, however, is quite limited. Cryopreservation could prolong their shelf-life, allowing for their ideal match to a recipient. In this study, porcine pulmonary valves were decellularized using detergents, either prior or after cryopreservation, and analyzed. Mechanical integrity was analyzed by uniaxial tensile testing, histoarchitecture by histological staining, and composition by DNA, collagen (hydroxyproline) and GAG (chondroitin sulfate) quantification. Residual sodium dodecyl sulfate (SDS) in the scaffold was quantified by applying a methylene blue activation assay (MBAS). Cryopreserved decellularized scaffolds (DC) and scaffolds that were decellularized after cryopreservation (CD) were compared to fresh valves (F), cryopreserved native valves (C), and decellularized only scaffolds (D). The E-modulus and tensile strength of decellularized (D) tissue showed no significant difference compared to DC and CD. The decellularization resulted in an overall reduction of DNA and GAG, with DC containing the lowest amount of GAGs. The DNA content in the valvular wall of the CD group was higher than in the D and DC groups. CD valves showed slightly more residual SDS than DC valves, which might be harmful to recipient cells. In conclusion, cryopreservation after decellularization was shown to be preferable over cryopreservation before decellularization. However, in vivo testing would be necessary to determine whether these differences are significant in biocompatibility or immunogenicity of the scaffolds. Absence of adverse effects on biomechanical stability of acellular heart valve grafts by cryopreservation, neither before nor after decellularization, allows the identification of best matching patients in a less time pressure dictated process, and therefore to an optimized use of a very limited, but best-suited heart valve prosthesis. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Physical activity and fatigue in chronic obstructive pulmonary disease - A population based study.
Andersson, Mikael; Stridsman, Caroline; Rönmark, Eva; Lindberg, Anne; Emtner, Margareta
2015-08-01
In subjects with chronic obstructive pulmonary disease (COPD), symptoms of fatigue, concomitant heart disease and low physical activity levels are more frequently described than in subjects without COPD. However, there are no population-based studies addressing the relationship between physical activity, fatigue and heart disease in COPD. The aim was to compare physical activity levels among subjects with and without COPD in a population based study, and to evaluate if concomitant heart disease and fatigue was associated to physical activity. In this, 470 subjects with COPD and 659 subjects without COPD (non-COPD) participated in examinations including structured interview and spirometry. A ratio of the forced expiratory volume in one second (FEV1)/best of forced vital capacity (FVC) and vital capacity (VC) < 0.7 was used to define COPD. Physical activity was assessed with the International Physical Activity Questionnaire (IPAQ), and fatigue with the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F). The prevalence of low physical activity was higher among subjects with FEV1 < 80% predicted compared to non-COPD subjects (22.4% vs. 14.6%, p = 0.041). The factors most strongly associated with low physical activity in subjects with COPD were older age, OR 1.52, (95% CI 1.12-2.06), a history of heart disease, OR 2.11 (1.10-4.08), and clinically significant fatigue, OR 2.33 (1.31-4.13); while obesity was the only significant factor among non-COPD subjects, OR 2.26 (1.17-4.35). Physical activity levels are reduced when lung function is decreased below 80% of predicted, and the factors associated with low physical activity are different among subject with and without COPD. We propose that the presence of fatigue and heart disease are useful to evaluate when identifying subjects for pulmonary rehabilitation. Copyright © 2015 Elsevier Ltd. All rights reserved.
Chen, Yu; Zhu, Li; Xu, Fei; Chen, Jun
2016-02-01
Heart failure is a major public health concern which contributes significantly to rising healthcare costs. Comprehensive discharge planning can improve health outcomes and reduce readmission rates which, in turn, can lead to cost savings. The aim of this project was to promote best practice in the discharge planning of heart failure patients admitted in the coronary care unit of Zhongshan Hospital. A clinical audit was undertaken using the Joanna Briggs Institute Practical Application of Clinical Evidence System tool. Five audit criteria that represent best practice recommendations for heart failure discharge planning were used. A baseline audit was conducted followed by the implementation of multiple strategies, and the project was finalized with a follow-up audit to determine change in practice. Improvements in practice were observed for all five criteria. The most significant improvements were in the following: completion of a discharge checklist (from 0% to 100% compliance), comprehensive (i.e. inclusion of six topics for self-care) discharge education for patients (from 7% to 100% compliance), and conducting a telephone follow-up (from 0% to 76% compliance). The compliance rates for the two remaining criteria, completion of a structured education for patients and scheduling an outpatient clinic visit, both increased from 93% to 100%.Strategies that were implemented to achieve change in practice included development of a local discharge planning checklist, provision of training for nurses, and development of resources. The project demonstrated positive changes in the discharge planning practices of nurses in the coronary care unit of Zhongshan Hospital. A formalized discharge planning is currently in place and plans for sustaining practice change are underway. A continuous cycle of audit and re-audit will need to be carried out in the future to determine the impact of this evidence implementation activity on heart failure patient outcomes.
Universal structures of normal and pathological heart rate variability.
Gañán-Calvo, Alfonso M; Fajardo-López, Juan
2016-02-25
The circulatory system of living organisms is an autonomous mechanical system softly tuned with the respiratory system, and both developed by evolution as a response to the complex oxygen demand patterns associated with motion. Circulatory health is rooted in adaptability, which entails an inherent variability. Here, we show that a generalized N-dimensional normalized graph representing heart rate variability reveals two universal arrhythmic patterns as specific signatures of health one reflects cardiac adaptability, and the other the cardiac-respiratory rate tuning. In addition, we identify at least three universal arrhythmic profiles whose presences raise in proportional detriment of the two healthy ones in pathological conditions (myocardial infarction; heart failure; and recovery from sudden death). The presence of the identified universal arrhythmic structures together with the position of the centre of mass of the heart rate variability graph provide a unique quantitative assessment of the health-pathology gradient.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Glass, L.; Hunter, P.; McCulloch, A.
1991-01-01
In recent years there has been a growth in interest in studying the heart from the perspective of the physical sciences: mechanics, fluid flow, electromechanics. This volume is the result of a workshop held in July 1989 at the Institute for Nonlinear Sciences at the University of California at San Diego that brought together scientists and clinicians with graduate students and postdoctoral fellows who share an interest in the heart. The chapters were prepared by the invited speakers as didactic reviews of their subjects but also include up-to-date results in their fields. Topics covered include the structure, mechanical properties, andmore » function of the heart and the myocardium, electrical activity of the heart and myocardium, and mathematical models of heart function. Individual chapters are abstracted separately.« less
Staged surgical palliation in hypoplastic left heart syndrome and its variants.
Delmo Walter, Eva Maria B; Hübler, Michael; Alexi-Meskishvili, Vladimir; Miera, Oliver; Weng, Yuguo; Loforte, Antonio; Berger, Felix; Hetzer, Roland
2009-01-01
Surgical options for infants with hypoplastic left heart syndrome (HLHS) and/or its variants are cardiac transplantation or the heart-preserving staged palliation with Norwood operation,followed by a two-staged Fontan procedure. We describe our 17-year experience with staged palliation of HLHS and/or its variants. Between December 1989 and December 2006, 64 patients with HLHS and/or its variants underwent a Norwood procedure (mean age/weight, 11.8+/-2.5 days/3.4 kg). Forty-four patients had classical HLHS. Twenty-eight percent had associated congenital cardiac, structural, and genetic anomalies. Subsequently, 25 patients underwent a bidirectional Glenn procedure (stage II) and 11 patients a modified Fontan procedure (stage III). Others await stage II and/or stage III. The follow-up was 143.2 patient-years. Including the learning curve, overall early mortality from 1989 to 1999 after the Norwood procedure was 39.06%. This decreased tremendously for the last seven years, and reduced to 12.8% in 2000 to 2003 until 0% in 2004 to 2006 (p < 0.005). The causes of mortality were sepsis, capillary leak,or heart failure. Three patients died between stages II and III. One patient underwent heart transplantation after the second stage because of heart failure. Among 34 Norwood survivors, four are slightly tachypneic from a mild pulmonary hyperperfusion; one presents symptoms of minimal brain disease. This report identified an outcome improvement after staged palliation of HLHS, attributed to an increase in experience and expertise gained over time. Lower operative weight, ascending aortic size, prolonged duration of cardiopulmonary bypass, and hypothermic circulatory arrest were identified to significantly influence early mortality after the Norwood procedure.
Dutra, Rosane Menezes Faria; Neves, Itamara Lucia Itagiba; Neves, Ricardo Simões; Atik, Edmar; de Paula Santos, Ubiratan
2014-01-01
OBJECTIVES: In this observational study, we evaluated the peripheral oxygen saturation (SpO2), heart rate, and blood pressure of children with cyanotic congenital heart disease who were undergoing dental extraction. METHODS: Forty-four patients between the ages of 6 and 12 years who underwent upper primary tooth extraction were included in the study. Of these, 20 patients were in the cyanotic congenital heart disease group and 24 were in the control group. RESULTS: Peripheral oxygen saturation, heart rate, and systolic blood pressure in the cyanotic congenital heart disease group varied quite significantly during the treatment protocol (p<0.05), with values of 80.5% (±7.6) to 82.8% (±7.8), 95.3 beats per minute (bpm) (±11.3) to 101.3 bpm (±9.8), and 93.6 mm Hg (±13,3) to 103.8 mm Hg (±12.7), respectively. The variations in the control group during the procedure were also significant. CONCLUSIONS: The changes observed during the study protocol, although statistically significant, were mild and lacked clinical relevance. The results indicate that dental treatment of children with cyanotic heart disease using a standardized protocol in decentralized offices without the support of a surgical center is safe. PMID:24838895
Heart rate and treatment effect in children with disruptive behavior disorders.
Stadler, Christina; Grasmann, Dörte; Fegert, Jörg M; Holtmann, Martin; Poustka, Fritz; Schmeck, Klaus
2008-09-01
To examine whether children with disruptive behavior disorders (DBDs; hyperkinetic conduct disorder, conduct disorder, hyperkinetic disorder) characterized by low heart rate profit less from an intensive cognitive behavioral intervention aimed at reducing impulsive, oppositional and aggressive behavior problems. Basal heart rate was studied in twenty-three children (aged 7-12 years) with DBD at the beginning of intervention comprising an intensive day-care treatment and parent training. The disruptive behavior of the child was assessed before treatment and after termination (12 weeks later). Therapy responders and non-responders were compared in regard to heart rate and other risk factors (cognitive functioning and socio-economic status). Statistical analyses yielded evidence for a significant reduction of disruptive problem behaviors (aggression, delinquency) that is more prominent in DBD children with high heart rate scores compared to patients with low heart rate scores. Heart rate was significantly lower in children who did not profit from therapy. A logistic regression analysis revealed that heart rate is a significant predictor for therapy success whereas other risk factors had no impact on therapy success. Further studies investigating biological and psychosocial predictors of treatment effectiveness are necessary. In addition, it might be helpful to consider different subtypes of aggressive behavior for selecting the best possible treatment options.
Baker, Laura A; Tuvblad, Catherine; Reynolds, Chandra; Zheng, Mo; Lozano, Dora Isabel; Raine, Adrian
2009-01-01
The genetic and environmental basis of a well-replicated association between antisocial behavior (ASB) and resting heart rate was investigated in a longitudinal twin study, based on two measurements between the ages of 9 and 14 years. ASB was defined as a broad continuum of externalizing behavior problems, assessed at each occasion through a composite measure based on parent ratings of trait aggression, delinquent behaviors, and psychopathic traits in their children. Parent ratings of ASB significantly decreased across age from childhood to early adolescence, although latent growth models indicated significant variation and twin similarity in the growth patterns, which were explained almost entirely by genetic influences. Resting heart rate at age 9-10 years old was inversely related to levels of ASB but not change patterns of ASB across age or occasions. Biometrical analyses indicated significant genetic influences on heart rate during childhood, as well as ASB throughout development from age 9 to 14. Both level and slope variation were significantly influenced by genetic factors. Of importance, the low resting heart rate and ASB association was significantly and entirely explained by their genetic covariation, although the heritable component of heart rate explained only a small portion (1-4%) of the substantial genetic variance in ASB. Although the effect size is small, children with low resting heart rate appear to be genetically predisposed toward externalizing behavior problems as early as age 9 years old.
Huang, Weijian; Su, Lan; Wu, Shengjie; Xu, Lei; Xiao, Fangyi; Zhou, Xiaohong; Ellenbogen, Kenneth A
2017-04-01
Clinical benefits from His bundle pacing (HBP) in heart failure patients with preserved and reduced left ventricular ejection fraction are still inconclusive. This study evaluated clinical outcomes of permanent HBP in atrial fibrillation patients with narrow QRS who underwent atrioventricular node ablation for heart failure symptoms despite rate control by medication. The study enrolled 52 consecutive heart failure patients who underwent attempted atrioventricular node ablation and HBP for symptomatic atrial fibrillation. Echocardiographic left ventricular ejection fraction and left ventricular end-diastolic dimension, New York Heart Association classification and use of diuretics for heart failure were assessed during follow-up visits after permanent HBP. Of 52 patients, 42 patients (80.8%) received permanent HBP and atrioventricular node ablation with a median 20-month follow-up. There was no significant change between native and paced QRS duration (107.1±25.8 versus 105.3±23.9 milliseconds, P =0.07). Left ventricular end-diastolic dimension decreased from the baseline ( P <0.001), and left ventricular ejection fraction increased from baseline ( P <0.001) in patients with a greater improvement in heart failure with reduced ejection fraction patients (N=20) than in heart failure with preserved ejection fraction patients (N=22). New York Heart Association classification improved from a baseline 2.9±0.6 to 1.4±0.4 after HBP in heart failure with reduced ejection fraction patients and from a baseline 2.7±0.6 to 1.4±0.5 after HBP in heart failure with preserved ejection fraction patients. After 1 year of HBP, the numbers of patients who used diuretics for heart failure decreased significantly ( P <0.001) when compared to the baseline diuretics use. Permanent HBP post-atrioventricular node ablation significantly improved echocardiographic measurements and New York Heart Association classification and reduced diuretics use for heart failure management in atrial fibrillation patients with narrow QRS who suffered from heart failure with preserved or reduced ejection fraction. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Acute hemodynamic effects of adaptive servo-ventilation in patients with heart failure.
Yamada, Shiro; Sakakibara, Mamoru; Yokota, Takashi; Kamiya, Kiwamu; Asakawa, Naoya; Iwano, Hiroyuki; Yamada, Satoshi; Oba, Koji; Tsutsui, Hiroyuki
2013-01-01
Adaptive servo-ventilation (ASV) improves cardiac function in patients with heart failure (HF). We compared the hemodynamics of control and HF patients, and identified the predictors for acute effects of ASV in HF. We performed baseline echocardiographic measurements and hemodynamic measurements at baseline and after 15 min of ASV during cardiac catheterization in 11 control and 34 HF patients. Heart rate and blood pressure did not change after ASV in either the control or HF group. Stroke volume index (SVI) decreased from 49.3±7.6 to 41.3±7.6 ml/m2 in controls (P<0.0001) but did not change in the HF patients (from 34.8±11.5 to 32.8±8.9 ml/m2, P=0.148). In the univariate analysis, pulmonary capillary wedge pressure (PCWP), mitral regurgitation (MR)/left atrial (LA) area, E/A, E/e', and the sphericity index defined by the ratio between the short-axis and long-axis dimensions of the left ventricle significantly correlated with % change of SVI from baseline during ASV. PCWP and MR/LA area were independent predictors by multivariate analysis. Moreover, responders (15 of 34 HF patients; 44%) categorized by an increase in SVI showed significantly higher PCWP, MR, and sphericity index. Left ventricular structure and MR, as well as PCWP, could predict acute favorable effects on hemodynamics by ASV therapy in HF patients.
Segerson, Nathan M; Wasmund, Stephen L; Abedin, Moeen; Pai, Rakesh K; Daccarett, Marcos; Akoum, Nazem; Wall, T Scott; Klein, Richard C; Freedman, Roger A; Hamdan, Mohamed H
2007-03-01
Heart rate turbulence (HRT) has been shown to be vagally mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) after a premature ventricular contraction (PVC) remains unclear. We sought to evaluate the relationship between HRT and the changes in peripheral SNA after PVCs. We recorded postganglionic muscle SNA during electrocardiogram monitoring in eight patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during (1) the dominant burst after the PVC (dominant burst area) and (2) the 10 seconds after the dominant burst (postburst SNA). The mean TO was 0.1% +/- 4.6%, and the mean TS was 6.1 +/- 6.6. The dominant burst area negatively correlated with TO (r = -0.50, P = .0002). The postburst SNA showed a significant positive correlation with TO (r = 0.44, P = .001) and a negative correlation with TS (r = -0.42, P = .002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease.
Gavurová, Beáta; Vagašová, Tatiana
2016-12-01
The aim of paper is to analyse the development of standardised mortality rates for ischemic heart diseases in relation to the income inequality in the regions of Slovakia. This paper assesses different types of income indicators, such as mean equivalised net income per household, Gini coefficient, unemployment rate, at risk of poverty threshold (60 % of national median), S80/S20 and their effect on mortality. Using data from the Slovak mortality database 1996-2013, the method of direct standardisation was applied to eliminate variances resulted from differences in age structures of the population across regions and over time. To examine the relationships between income indicators and standardised mortality rates, we used the tools of descriptive statistics and methods of correlation and regression analysis. At first, we show that Slovakia has the worst values of standardised mortality rates for ischemic heart diseases in EU countries. Secondly, mortality rates are significantly higher for males compared with females. Thirdly, mortality rates are improving from Eastern Slovakia to Western Slovakia; additionally, high differences in the results of variability are seen among Slovak regions. Finally, the unemployment rate, the poverty rate and equivalent disposable income were statistically significant income indicators. Main contribution of paper is to demonstrate regional differences between mortality and income inequality, and to point out the long-term unsatisfactory health outcomes.
Rossini, Kamila Fernanda; de Oliveira, Camila Andrea; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana
2017-01-01
Background The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. Results LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. Conclusion GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. PMID:28678925
Sacks, Michael S; Mirnajafi, Ali; Sun, Wei; Schmidt, Paul
2006-11-01
The present review surveys significant developments in the biomechanical characterization and computational simulation of biologically derived chemically cross-linked soft tissues, or 'heterograft' biomaterials, used in replacement bioprosthetic heart valve (BHV). A survey of mechanical characterization techniques, relevant mechanical properties and computational simulation approaches is presented for both the source tissues and cross-linked biomaterials. Since durability remains the critical problem with current bioprostheses, changes with the mechanical behavior with fatigue are also presented. Moreover, given the complex nature of the mechanical properties of heterograft biomaterials it is not surprising that most constitutive (stress-strain) models, historically used to characterize their behavior, were oversimplified. Simulations of BHV function utilizing these models have inevitably been inaccurate. Thus, more recent finite element simulations utilizing nonlinear constitutive models, which achieve greater model fidelity, are reviewed. An important conclusion of this review is the need for accurate constitutive models, rigorously validated with appropriate experimental data, in order that the design benefits of computational models can be realized. Finally, for at least the coming 20 years, BHVs fabricated from heterograft biomaterials will continue to be extensively used, and will probably remain as the dominant valve design. We should thus recognize that rational, scientifically based approaches to BHV biomaterial development and design can lead to significantly improved BHV, over the coming decades, which can potentially impact millions of patients worldwide with heart valve disease.
Cook, Jason A; Shah, Keyur B; Quader, Mohammed A; Cooke, Richard H; Kasirajan, Vigneshwar; Rao, Kris K; Smallfield, Melissa C; Tchoukina, Inna; Tang, Daniel G
2015-12-01
The total artificial heart (TAH) is a form of mechanical circulatory support in which the patient's native ventricles and valves are explanted and replaced by a pneumatically powered artificial heart. Currently, the TAH is approved for use in end-stage biventricular heart failure as a bridge to heart transplantation. However, with an increasing global burden of cardiovascular disease and congestive heart failure, the number of patients with end-stage heart failure awaiting heart transplantation now far exceeds the number of available hearts. As a result, the use of mechanical circulatory support, including the TAH and left ventricular assist device (LVAD), is growing exponentially. The LVAD is already widely used as destination therapy, and destination therapy for the TAH is under investigation. While most patients requiring mechanical circulatory support are effectively treated with LVADs, there is a subset of patients with concurrent right ventricular failure or major structural barriers to LVAD placement in whom TAH may be more appropriate. The history, indications, surgical implantation, post device management, outcomes, complications, and future direction of the TAH are discussed in this review.
Chamber identity programs drive early functional partitioning of the heart.
Mosimann, Christian; Panáková, Daniela; Werdich, Andreas A; Musso, Gabriel; Burger, Alexa; Lawson, Katy L; Carr, Logan A; Nevis, Kathleen R; Sabeh, M Khaled; Zhou, Yi; Davidson, Alan J; DiBiase, Anthony; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Zon, Leonard I
2015-08-26
The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction.
Structural pathways and prevention of heart failure and sudden death.
Pacifico, Antonio; Henry, Philip D
2003-07-01
We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.
Sharma, A K; Dhingra, S; Khaper, N; Singal, P K
2007-09-01
Changes in oxidative stress and apoptotic process were studied during the progression of a compensated hypertrophy to a decompensated heart failure in guinea pigs. Banding of the ascending aorta resulted in heart hypertrophy. At 10 wk, ventricle-to-body weight ratio and thickness of the interventricular septum as well as the left ventricular wall were increased significantly. Although fractional shortening and ejection fraction were decreased, there were no signs of heart failure. Furthermore, there was no increase in wet-to-dry weight ratios for the lungs and liver at this stage. However, at 20 wk, heart failure was characterized by a significant depression in heart function as indicated by a decrease in fractional shortening, and ejection fraction and a lesser increase in wall thickness from diastole to systole. Animals also showed clinical signs of heart failure, and the wet-to-dry weight ratios of the lungs and liver were significantly higher. Cardiomyocyte oxidative stress was significantly higher in the 20-wk aortic-banded group. The ratio of Bax to Bcl-xl showed an increase at 10 wk, and there was a further increase at 20 wk. Mitochondrial membrane potential in the aortic-banded animals was significantly decreased at 10 and 20 wk. Cytochrome c levels were higher in the cytosol compared with the mitochondria, leading to a considerable increase in the expression of p17 subunit of caspase-3. At 20 wk, both early and late stages of apoptosis were observed in isolated cardiomyocytes. It is suggested that an increase in oxidative stress initiates mitochondrial death pathway during the hypertrophic stage, leading to apoptosis and heart failure at a later stage.
Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction.
Pal, Nikhil; Sivaswamy, Nadiya; Mahmod, Masliza; Yavari, Arash; Rudd, Amelia; Singh, Satnam; Dawson, Dana K; Francis, Jane M; Dwight, Jeremy S; Watkins, Hugh; Neubauer, Stefan; Frenneaux, Michael; Ashrafian, Houman
2015-11-03
Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF. We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [o2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in o2 peak. Secondary outcomes included tissue Doppler-derived E/e' at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in o2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg(-1)·min(-1); P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable. Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354573. © 2015 The Authors.
Zoair, Amr; Mawlana, Wegdan; Abo-Elenin, Amany; Korrat, Mostafa
2015-12-01
Remodeling of the heart following injury affects the morbidity and mortality in children presented with heart failure (HF). Heart-type fatty acid binding protein (H-FABP) is a novel biomarker that could be of help to predict the prognosis and risk stratification in those children. We aimed to evaluate the diagnostic and prognostic value of H-FABP in children with heart failure before and after treatment. The study was conducted as a prospective cohort study. It included 30 children with HF as a patient group and 20 healthy children matched for age and sex as a control group. Echocardiographic assessment of the heart was done using conventional Doppler echocardiography. Serum levels of (H-FABP) were measured using enzyme-linked immunosorbent assay before and after treatment of HF. All patients were observed during follow-up period of 3 months. There was a significant difference in the serum level of H-FABP in our patients before treatment (5.278 ± 3.253 ng/ml) compared with after treatment (2.089 ± 0.160 ng/ml) with significant difference compared with the control group. There was a significant increase in the serum level of H-FABP with increase in the severity of heart failure according to Ross classification. Significant increase in the H-FABP was associated with adverse outcome. Serum levels of H-FABP strongly correlated with clinical and echocardiographic assessment of LV performance of children with HF, and its levels significantly increased in children with adverse outcome suggesting its value as a useful diagnostic and prognostic predictor (with high sensitivity and specificity).
Capturing structure and function in an embryonic heart with biophotonic tools
Karunamuni, Ganga H.; Gu, Shi; Ford, Matthew R.; Peterson, Lindsy M.; Ma, Pei; Wang, Yves T.; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko
2014-01-01
Disturbed cardiac function at an early stage of development has been shown to correlate with cellular/molecular, structural as well as functional cardiac anomalies at later stages culminating in the congenital heart defects (CHDs) that present at birth. While our knowledge of cellular and molecular steps in cardiac development is growing rapidly, our understanding of the role of cardiovascular function in the embryo is still in an early phase. One reason for the scanty information in this area is that the tools to study early cardiac function are limited. Recently developed and adapted biophotonic tools may overcome some of the challenges of studying the tiny fragile beating heart. In this chapter, we describe and discuss our experience in developing and implementing biophotonic tools to study the role of function in heart development with emphasis on optical coherence tomography (OCT). OCT can be used for detailed structural and functional studies of the tubular and looping embryo heart under physiological conditions. The same heart can be rapidly and quantitatively phenotyped at early and again at later stages using OCT. When combined with other tools such as optical mapping (OM) and optical pacing (OP), OCT has the potential to reveal in spatial and temporal detail the biophysical changes that can impact mechanotransduction pathways. This information may provide better explanations for the etiology of the CHDs when interwoven with our understanding of morphogenesis and the molecular pathways that have been described to be involved. Future directions for advances in the creation and use of biophotonic tools are discussed. PMID:25309451
Mascherbauer, Julia; Kammerlander, Andreas A.; Zotter-Tufaro, Caroline; Aschauer, Stefan; Duca, Franz; Dalos, Daniel; Winkler, Susanne; Schneider, Matthias; Bergler-Klein, Jutta; Bonderman, Diana
2017-01-01
Background Diastolic dysfunction of the left ventricle is common but frequently under-diagnosed. Particularly in advanced stages affected patients may present with significant functional tricuspid regurgitation (TR) as the most prominent sign on echocardiography. The underlying left ventricular pathology may eventually be missed and symptoms of heart failure are attributed to TR, with respective therapeutic consequences. The aim of the present study was to determine prevalence and mechanisms underlying TR evolution in heart failure with preserved ejection fraction (HFpEF). Methods and results Consecutive HFpEF patients were enrolled in this prospective, observational study. Confirmatory diagnostic tests including echocardiography and invasive hemodynamic assessments were performed. Of the 175 patients registered between 2010 and 2014, 51% had significant (moderate or severe) TR without structural abnormalities of the tricuspid valve. Significant hemodynamic differences between patients with and without relevant TR were encountered. These included elevated pulmonary vascular resistance (p = 0.038), reduced pulmonary arterial compliance (PAC, p = 0.005), and elevated left ventricular filling pressures (p = 0.039) in the TR group. Multivariable binary logistic regression analysis revealed diastolic pulmonary artery pressure (p = 0.029) and PAC (p = 0.048) as independent determinants of TR. Patients were followed for 18.1±14.1 months, during which 32% had a cardiac event. While TR was associated with outcome in the univariable analysis, it failed to predict event-free survival in the multivariable model. Conclusions The presence of ´isolated´ functional TR should prompt the suspicion of HFpEF. Our data show that significant TR is a marker of advanced HFpEF but neither an isolated entity nor independently associated with event-free survival. PMID:28199339
Wang, Yuehui; Sun, Weixia; Du, Bing; Miao, Xiao; Bai, Yang; Xin, Ying; Tan, Yi; Cui, Wenpeng; Liu, Bin; Cui, Taixing; Epstein, Paul N; Fu, Yaowen; Cai, Lu
2013-02-15
MG-132, a proteasome inhibitor, can upregulate nuclear factor (NF) erythroid 2-related factor 2 (Nrf2)-mediated antioxidative function and downregulate NF-κB-mediated inflammation. The present study investigated whether through the above two mechanisms MG-132 could provide a therapeutic effect on diabetic cardiomyopathy in the OVE26 type 1 diabetic mouse model. OVE26 mice develop hyperglycemia at 2-3 wk after birth and exhibit albuminuria and cardiac dysfunction at 3 mo of age. Therefore, 3-mo-old OVE26 diabetic and age-matched control mice were intraperitoneally treated with MG-132 at 10 μg/kg daily for 3 mo. Before and after MG-132 treatment, cardiac function was measured by echocardiography, and cardiac tissues were then subjected to pathological and biochemical examination. Diabetic mice showed significant cardiac dysfunction, including increased left ventricular systolic diameter and wall thickness and decreased left ventricular ejection fraction with an increase of the heart weight-to-tibia length ratio. Diabetic hearts exhibited structural derangement and remodeling (fibrosis and hypertrophy). In diabetic mice, there was also increased systemic and cardiac oxidative damage and inflammation. All of these pathogenic changes were reversed by MG-132 treatment. MG-132 treatment significantly increased the cardiac expression of Nrf2 and its downstream antioxidant genes with a significant increase of total antioxidant capacity and also significantly decreased the expression of IκB and the nuclear accumulation and DNA-binding activity of NF-κB in the heart. These results suggest that MG-132 has a therapeutic effect on diabetic cardiomyopathy in OVE26 diabetic mice, possibly through the upregulation of Nrf2-dependent antioxidative function and downregulation of NF-κB-mediated inflammation.
Mann, Sarah L.; Selby, Edward A.; Bates, Marsha E.; Contrada, Richard J.
2016-01-01
High frequency heart rate variability (HRV) is a measure of neurocardiac communication thought to reflect predominantly parasympathetic cardiac regulation. Low HRV has been associated empirically with clinical and subclinical levels of anxiety and depression and, more recently, high levels of HRV have been associated with better performance on some measures of executive functioning (EF). These findings have offered support for theories proposing HRV as an index measure of a broad, self-regulatory capacity underlying aspects of emotion regulation and executive control. This study sought to test that proposition by using a structural equation modeling approach to examine the relationships of HRV to negative affect (NA) and EF in a large sample of U.S. adults ages 30s–80s. HRV was modeled as a predictor of an NA factor (self-reported trait anxiety and depression symptoms) and an EF factor (performance on three neuropsychological tests tapping facets of executive abilities). Alternative models also were tested to determine the utility of HRV for predicting NA and EF, with and without statistical control of demographic and health-related covariates. In the initial structural model, HRV showed a significant positive relationship to EF and a nonsignificant relationship to NA. In a covariate-adjusted model, HRV’s associations with both constructs were nonsignificant. Age emerged as the only significant predictor of NA and EF in the final model, showing inverse relationships to both. Findings may reflect population and methodological differences from prior research; they also suggest refinements to the interpretations of earlier findings and theoretical claims regarding HRV. PMID:26168884
A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice
DOE Office of Scientific and Technical Information (OSTI.GOV)
Walker, Mary K., E-mail: mwalker@salud.unm.edu; Boberg, Jason R.; Walsh, Mary T.
Oral gavage dosing can induce stress and potentially confound experimental measurements, particularly when blood pressure and heart rate are endpoints of interest. Thus, we developed a pill formulation that mice would voluntarily consume and tested the hypothesis that pill dosing would be significantly less stressful than oral gavage. C57Bl/6 male mice were singly housed and on four consecutive days were exposed to an individual walking into the room (week 1, control), a pill being placed into the cage (week 2), and a dose of water via oral gavage (week 3). Blood pressure and heart rate were recorded by radiotelemetry continuouslymore » for 5 h after treatment, and feces collected 6–10 h after treatment for analysis of corticosterone metabolites. Both pill and gavage dosing significantly increased mean arterial pressure (MAP) during the first hour, compared to control. However, the increase in MAP was significantly greater after gavage and remained elevated up to 5 h, while MAP returned to normal within 2 h after a pill. Neither pill nor gavage dosing significantly increased heart rate during the first hour, compared to control; however, pill dosing significantly reduced heart rate while gavage significantly increased heart rate 2–5 h post dosing. MAP and heart rate did not differ 24 h after dosing. Lastly, only gavage dosing significantly increased fecal corticosterone metabolites, indicating a systemic stress response via activation of the hypothalamic–pituitary–adrenal axis. These data demonstrated that this pill dosing method of mice is significantly less stressful than oral gavage. -- Highlights: ► Developed a novel oral dosing method using a pill that mice will readily consume. ► Assessed stress by blood pressure, heart rate, and fecal corticosterone metabolites. ► Demonstrated that pill dosing is significantly less stressful than oral gavage.« less
Cnota, James F; Gupta, Resmi; Michelfelder, Erik C; Ittenbach, Richard F
2011-11-01
To describe congenital heart disease death rates in infants born between 34 and 40 weeks, estimate the relationship between gestational age and congenital heart disease infant death rates, and compare congenital heart disease death rates across 1- and 2-week intervals in gestational age. The 2000 to 2003 national linked birth/infant death cohort datasets were obtained. Congenital heart disease deaths were identified by using International Statistical Classification of Diseases, 10th Revision codes. Proportional death rates were calculated by using congenital heart disease deaths and all live births. The relationship between congenital heart disease death rates and gestational age was determined. Death rates were compared across intervals. A total of 14.9 million records were analyzed. Congenital heart disease deaths occurred in 4736 infants (0.04%) born between 34 and 40 weeks. There was a significant, negative linear relationship between congenital heart disease death rate and gestational age (R(2) = 0.97). Comparisons across 1-week intervals varied (P = .02-.23). All 2-week intervals were statistically significant (P < .01). Congenital heart disease death rates decrease as gestational age approaches 40 weeks. These results should be considered before elective delivery for the sole indication of prenatally diagnosed congenital heart disease. Copyright © 2011 Mosby, Inc. All rights reserved.
Altered carnitine transport in pressure-overload hypertrophied rat hearts
DOE Office of Scientific and Technical Information (OSTI.GOV)
O'Rourke, B.; Foster, K.; Reibel, D.K.
1986-03-01
The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L-/sup 14/C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 ..mu..M carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. Themore » reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 ..mu..M carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart.« less
Zhang, WB; Du, QJ; Li, H; Sun, AJ; Qiu, ZH; Wu, CN; Zhao, G; Gong, H; Hu, K; Zou, YZ; Ge, JB
2012-01-01
End-stage hypertensive heart disease is an increasing cause of cardiac mortality. Therefore, the current study focused on the cardiac remodelling from hypertrophy to fibrosis in old-aged spontaneously hypertensive rats (SHRs), and explored the therapeutic effects of Rosuvastatin and its possible mechanism(s) of action. Spontaneously hypertensive rats at age 52 weeks were randomly divided into three groups, the first two to receive Rosuvastatin at a dose of 20 mg/kg/day and 40 mg/kg/day, respectively, and the third to receive placebo, which was to be compared with Wistar-Kyoto as controls. After 2-month treatment, SBP, heart to body weight ratio (HW/BW%) and echocardiographic features were evaluated, followed by haematoxylin and eosin and Masson trichrome staining in conjunction with qPCR of foetal gene expressions. Transferase-mediated dUTP nick-end labelling assay and immunofluorescent labelling for active caspase-3 were used to detect the apoptotic cardiomyocytes. Signaling pathways involved were examined by using western blot. Old-aged SHR developed end-stage hypertensive heart disease characterized by significant enhancement of HW/BW%, LVAWd and LVPWd, and decreased LVEF and LVFS, accompanied by cardiomyocytes enlargement and fibrosis along with activation of foetal gene programme. Cardiac apoptosis increased significantly during the transition process. Rosuvastatin reduced hypertrophy significantly via AT1 Receptor-PKCβ2/α-ERK-c-fos pathway; protected myocardium against apoptosis via Akt-FOXO1, Bcl-2 family and survivin pathways and consequently suppressed the caspase-3 activity. The present study revealed that old-aged SHRs developed cardiac remodelling from hypertrophy to fibrosis via cardiac apoptosis during the end stage of hypertensive heart disease. These pathological changes might be the consequence of activation of AT1 Receptor-PKCβ2/α-ERK-c-fos and AKT-FOXO1/Bcl-2/survivin/Caspase3 signaling. Rosuvastatin effectively attenuated the structural changes by reversing the signaling transductions involved. PMID:22288611
Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation.
Amino, Mari; Yoshioka, Koichiro; Fujibayashi, Daisuke; Hashida, Tadashi; Furusawa, Yoshiya; Zareba, Wojciech; Ikari, Yuji; Tanaka, Etsuro; Mori, Hidezo; Inokuchi, Sadaki; Kodama, Itsuo; Tanabe, Teruhisa
2010-03-01
A previous study from our laboratory has shown that a single targeted heavy ion irradiation (THIR; 15 Gy) to rabbit hearts increases connexin43 (Cx43) expression for 2 wk in association with an improvement of conduction, a decrease of the spatial inhomogeneity of repolarization, and a reduction of vulnerability to ventricular arrhythmias after myocardial infarction. This study investigated the time- and dose-dependent effects of THIR (5-15 Gy) on Cx43 expression in normal rabbit hearts (n = 45). Five rabbits without THIR were used as controls. A significant upregulation of Cx43 protein and mRNA in the ventricular myocardium was recognized by immunohistochemistry, Western blotting, and real-time PCR from 2 wk up to 1 yr after a single THIR at 15 Gy. THIR > or =10 Gy caused a significant dose-dependent increase of Cx43 protein and mRNA 2 wk after THIR. Anterior, lateral, and posterior free wall of the left ventricle, interventricular septum, and right ventricular free wall were affected similarly by THIR in terms of Cx43 upregulation. The radiation-induced increase of immunolabeled Cx43 was observed not only at the intercalated disk region but also at the lateral surface of ventricular myocytes. The increase of immunoreactive Cx43 protein was predominant in the membrane fraction insoluble in Triton X-100, that is the Cx43 in the sarcolemma. In vivo examinations of the rabbits 1 yr after THIR (15 Gy) revealed no significant changes in ECGs and echocardiograms (left ventricular dimensions, contractility, and diastolic function), indicating no apparent late radiation injury. A single application of THIR causes upregulation and altered cellular distribution of Cx43 in the ventricles lasting for at least 1 yr. This long-lasting remodeling effect on gap junctions may open the pathway to novel therapy against life threatening ventricular arrhythmias in structural heart disease.
An effective physical fitness program for small and medium-sized enterprises.
Tsai, Han Hui; Peng, Shu Mei; Yeh, Ching Ying; Chen, Chiou Jong; Chen, Ruey Yu
2011-01-01
The aim of this study is to develop a practicable worksite physical fitness program for small and medium-sized enterprises (SMEs). Community-based intervention consisting of a three-month exercise course was conducted, and its benefits evaluated. A self-administrated structured questionnaire and physical fitness examination were designed to compare the difference between pre and post intervention. A total of 133 SME workers completed the lifestyle/exercise course and filled out the questionnaire, but 16 were excluded from the exercise group due to health reasons. After the intervention, health indicators such as weight, blood pressure, resting heart rate, waistline, BMI, front and back trunk flexibility, abdominal muscle durability and back muscle strength were significantly improved, and improvements in musculoskeletal disorders were seen in reduced neck pain (18.8%), wrist pain (17.4%), and upper/lower back pain (8.7% and 21.7%, respectively). Cardiovascular risk factors (BMI and resting heart rate) showed a significant improvement related to frequent participation in the program (p=0.02), and the exercise group reported a significant difference in overall health (p=0.02). This study has demonstrated an effective approach to community-based fitness intervention through SMEs.
Thompson, Keith A; Morrissey, Ryan P; Phan, Anita; Schwarz, Ernst R
2012-08-01
To determine the effects of the US economy on heart failure hospitalization rates. The recession was associated with worsening unemployment, loss of private insurance and prescription medication benefits, medication nonadherence, and ultimately increased rates of hospitalization for heart failure. We compared hospitalization rates at a large, single, academic medical center from July 1, 2006 to February 28, 2007, a time of economic stability, and July 1, 2008 to February 28, 2009, a time of economic recession in the United States. Significantly fewer patients had private medical insurance during the economic recession than during the control period (36.5% vs 46%; P = 0.04). Despite this, there were no differences in the heart failure hospitalization or readmission rates, length of hospitalization, need for admission to an intensive care unit, in-hospital mortality, or use of guideline-recommended heart failure medications between the 2 study periods. We conclude that despite significant effects on medical insurance coverage, rates of heart failure hospitalization at our institution were not significantly affected by the recession. Additional large-scale population-based research is needed to better understand the effects of fluctuations in the US economy on heart failure hospitalization rates. © 2012 Wiley Periodicals, Inc.
The effects of gum chewing while walking on physical and physiological functions.
Hamada, Yuka; Yanaoka, Takuma; Kashiwabara, Kyoko; Kurata, Kuran; Yamamoto, Ryo; Kanno, Susumu; Ando, Tomonori; Miyashita, Masashi
2018-04-01
[Purpose] This study examined the effects of gum chewing while walking on physical and physiological functions. [Subjects and Methods] This study enrolled 46 male and female participants aged 21-69 years. In the experimental trial, participants walked at natural paces for 15 minutes while chewing two gum pellets after a 1-hour rest period. In the control trial, participants walked at natural paces for 15 minutes after ingesting powder containing the same ingredient, except the gum base, as the chewing gum. Heart rates, walking distances, walking speeds, steps, and energy expenditure were measured. [Results] Heart rates during walking and heart rate changes (i.e., from at rest to during walking) significantly increased during the gum trial compared with the control trial. Walking distance, walking speed, walking heart rate, and heart rate changes in male participants and walking heart rate and heart rate changes in female participants were significantly higher during the gum trial than the control trial. In middle-aged and elderly male participants aged ≥40 years, walking distance, walking speed, steps, and energy expenditure significantly increased during the gum trial than the control trial. [Conclusion] Gum chewing while walking measurably affects physical and physiological functions.
The effects of gum chewing while walking on physical and physiological functions
Hamada, Yuka; Yanaoka, Takuma; Kashiwabara, Kyoko; Kurata, Kuran; Yamamoto, Ryo; Kanno, Susumu; Ando, Tomonori; Miyashita, Masashi
2018-01-01
[Purpose] This study examined the effects of gum chewing while walking on physical and physiological functions. [Subjects and Methods] This study enrolled 46 male and female participants aged 21–69 years. In the experimental trial, participants walked at natural paces for 15 minutes while chewing two gum pellets after a 1-hour rest period. In the control trial, participants walked at natural paces for 15 minutes after ingesting powder containing the same ingredient, except the gum base, as the chewing gum. Heart rates, walking distances, walking speeds, steps, and energy expenditure were measured. [Results] Heart rates during walking and heart rate changes (i.e., from at rest to during walking) significantly increased during the gum trial compared with the control trial. Walking distance, walking speed, walking heart rate, and heart rate changes in male participants and walking heart rate and heart rate changes in female participants were significantly higher during the gum trial than the control trial. In middle-aged and elderly male participants aged ≥40 years, walking distance, walking speed, steps, and energy expenditure significantly increased during the gum trial than the control trial. [Conclusion] Gum chewing while walking measurably affects physical and physiological functions. PMID:29706720
Rovers minimize human disturbance in research on wild animals.
Le Maho, Yvon; Whittington, Jason D; Hanuise, Nicolas; Pereira, Louise; Boureau, Matthieu; Brucker, Mathieu; Chatelain, Nicolas; Courtecuisse, Julien; Crenner, Francis; Friess, Benjamin; Grosbellet, Edith; Kernaléguen, Laëtitia; Olivier, Frédérique; Saraux, Claire; Vetter, Nathanaël; Viblanc, Vincent A; Thierry, Bernard; Tremblay, Pascale; Groscolas, René; Le Bohec, Céline
2014-12-01
Investigating wild animals while minimizing human disturbance remains an important methodological challenge. When approached by a remote-operated vehicle (rover) which can be equipped to make radio-frequency identifications, wild penguins had significantly lower and shorter stress responses (determined by heart rate and behavior) than when approached by humans. Upon immobilization, the rover-unlike humans-did not disorganize colony structure, and stress rapidly ceased. Thus, rovers can reduce human disturbance of wild animals and the resulting scientific bias.
Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling
Yamaguchi, Osamu; Higuchi, Yoshiharu; Hirotani, Shinichi; Kashiwase, Kazunori; Nakayama, Hiroyuki; Hikoso, Shungo; Takeda, Toshihiro; Watanabe, Tetsuya; Asahi, Michio; Taniike, Masayuki; Matsumura, Yasushi; Tsujimoto, Ikuko; Hongo, Kenichi; Kusakari, Yoichiro; Kurihara, Satoshi; Nishida, Kazuhiko; Ichijo, Hidenori; Hori, Masatsugu; Otsu, Kinya
2003-01-01
Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis. PMID:14665690
Automaticity in acute ischemia: Bifurcation analysis of a human ventricular model
NASA Astrophysics Data System (ADS)
Bouchard, Sylvain; Jacquemet, Vincent; Vinet, Alain
2011-01-01
Acute ischemia (restriction in blood supply to part of the heart as a result of myocardial infarction) induces major changes in the electrophysiological properties of the ventricular tissue. Extracellular potassium concentration ([Ko+]) increases in the ischemic zone, leading to an elevation of the resting membrane potential that creates an “injury current” (IS) between the infarcted and the healthy zone. In addition, the lack of oxygen impairs the metabolic activity of the myocytes and decreases ATP production, thereby affecting ATP-sensitive potassium channels (IKatp). Frequent complications of myocardial infarction are tachycardia, fibrillation, and sudden cardiac death, but the mechanisms underlying their initiation are still debated. One hypothesis is that these arrhythmias may be triggered by abnormal automaticity. We investigated the effect of ischemia on myocyte automaticity by performing a comprehensive bifurcation analysis (fixed points, cycles, and their stability) of a human ventricular myocyte model [K. H. W. J. ten Tusscher and A. V. Panfilov, Am. J. Physiol. Heart Circ. Physiol.AJPHAP0363-613510.1152/ajpheart.00109.2006 291, H1088 (2006)] as a function of three ischemia-relevant parameters [Ko+], IS, and IKatp. In this single-cell model, we found that automatic activity was possible only in the presence of an injury current. Changes in [Ko+] and IKatp significantly altered the bifurcation structure of IS, including the occurrence of early-after depolarization. The results provide a sound basis for studying higher-dimensional tissue structures representing an ischemic heart.
Mandich Crovetto, D; Alonso Charterina, S; Jiménez López-Guarch, C; Pont Vilalta, M; Pérez Núñez, M; de Pablo Gafas, A; Escribano Subías, P
2016-01-01
To use multidetector computed tomography (MDCT) to evaluate the structural changes in the right heart and pulmonary arteries that occur in patients with severe pulmonary hypertension treated by double lung transplantation. This was a retrospective study of 21 consecutive patients diagnosed with severe pulmonary hypertension who underwent double lung transplantation at our center between 2010 and 2014. We analyzed the last MDCT study done before lung transplantation and the first MDCT study done after lung transplantation. We recorded the following variables: diameter of the pulmonary artery trunk, ratio of the diameter of the pulmonary artery trunk to the diameter of the ascending aorta, diameter of the right ventricle, ratio of the diameter of the left ventricle to the diameter of the right ventricle, and eccentricity index. Statistical analysis consisted of the comparison of the means of the variables recorded. In all cases analyzed, the MDCT study done a mean of 24±14 days after double lung transplantation showed a significant reduction in the size of the right heart chambers, with improved indices of ventricular interdependency index, and reduction in the size of the pulmonary artery trunk (p<0.001 for all the variables analyzed). Patients with pulmonary hypertension treated by double lung transplantation present early reverse remodeling of the changes in the structures of the right heart and pulmonary arterial tree. MDCT is useful for detecting these changes. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.
Westhoff-Bleck, Mechthild; Schieffer, Bernhard; Tegtbur, Uwe; Meyer, Gerd Peter; Hoy, Ludwig; Schaefer, Arnd; Tallone, Ezequiel Marcello; Tutarel, Oktay; Mertins, Ramona; Wilmink, Lena Mara; Anker, Stefan D; Bauersachs, Johann; Roentgen, Philipp
2013-12-05
Exercise training safely and efficiently improves symptoms in patients with heart failure due to left ventricular dysfunction. However, studies in congenital heart disease with systemic right ventricle are scarce and results are controversial. In a randomised controlled study we investigated the effect of aerobic exercise training on exercise capacity and systemic right ventricular function in adults with d-transposition of the great arteries after atrial redirection surgery (28.2 ± 3.0 years after Mustard procedure). 48 patients (31 male, age 29.3 ± 3.4 years) were randomly allocated to 24 weeks of structured exercise training or usual care. Primary endpoint was the change in maximum oxygen uptake (peak VO2). Secondary endpoints were systemic right ventricular diameters determined by cardiac magnetic resonance imaging (CMR). Data were analysed per intention to treat analysis. At baseline peak VO2 was 25.5 ± 4.7 ml/kg/min in control and 24.0 ± 5 ml/kg/min in the training group (p=0.3). Training significantly improved exercise capacity (treatment effect for peak VO2 3.8 ml/kg/min, 95% CI: 1.8 to 5.7; p=0.001), work load (p=0.002), maximum exercise time (p=0.002), and NYHA class (p=0.046). Systemic ventricular function and volumes determined by CMR remained unchanged. None of the patients developed signs of cardiac decompensation or arrhythmias while on exercise training. Aerobic exercise training did not detrimentally affect systemic right ventricular function, but significantly improved exercise capacity and heart failure symptoms. Aerobic exercise training can be recommended for patients following atrial redirection surgery to improve exercise capacity and to lessen or prevent heart failure symptoms. ( ClinicalTrials.gov #NCT00837603). © 2013.
Gottwald, E; Gottwald, M; Dhein, S
1998-01-01
Objective—To examine how epicardial activation and repolarisation patterns change in the course of ischaemia, and how these changes are related to the underlying histological structures. Methods—Langendorff perfused isolated rabbit hearts were submitted to 30 minutes of left anterior descending coronary artery occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was plotted during the various experimental phases. Activation time points were determined as t(dU/dtmin) and repolarisation time points as t(dU/dtmax). From these data the local activation-recovery interval (ARI), its dispersion (SD of ARI), and the geometry of the activation spread could be analysed. After the experiments the hearts were processed histologically and the mapping data were projected onto histological slides. Results—There was elevation of the ST segment within the occluded area, which recovered during reperfusion. Within this area, ARI was significantly shortened and its dispersion was maximally enhanced. The enhancement of dispersion was pronounced at sites of histological inhomogeneity like fat, connective tissue, or vessels. There was also a change in the preferential direction of activation spread within the occluded zone with a marked transverse propagation of the activation wavefront, whereas under normal conditions the activation followed the longitudinal fibre axis. In addition, the total activation time in the occluded area was significantly prolonged. Conclusions—Ischaemia alters the local activation pattern with enhanced dispersion, especially at sites of histological irregularity, transverse shift of the activation waves, and a general slowing of conduction, which may explain the increased susceptibility to arrhythmia in hearts with enhanced histological irregularities—for example, an infarct or in multi-infarcted hearts, or after myocarditis. Keywords: dispersion; epicardial activation-recovery interval; ischaemia PMID:9659194
The Evolution of an Adult Congenital Heart Surgery Program: The Emory System.
Kogon, Brian; Rosenblum, Joshua; Alsoufi, Bahaaldin; Shashidharan, Subhadra; Book, Wendy
2017-01-01
The Emory Adult Congenital Heart (Emory University, Atlanta, GA) program was founded in 2001. In 2004, the surgical component transitioned from a pediatric facility to an adult facility. The aim of this article is characterize the program as a whole, outline changes in the program, and discuss the challenges of the transition process. Between 2001 and 2015, changes in program structure and personnel were evaluated. There has been significant growth of the program between 2001 and 2015. There are currently 19 half-day clinics per week, with 2,700 clinic visits per year. There are six cardiologists, three congenital cardiac surgeons, two sonographers, one advanced practice provider, and one social worker dedicated to the program. There are Accreditation Council for Graduate Medical Education-accredited adult congenital cardiology and congenital cardiac surgery fellowships. One thousand forty-four operations were performed between 2001 and 2015. There were 828 open-heart operations, of which 581 (70%) were re-operations. Over the study period, the number of yearly operations increased from 30 to 119, and the mean age at surgery increased from 22 to 35 years. Over time, more of the operations were performed at the adult hospital: increasing from 3% in 2001 to 82% in 2015, and more of the operations were performed by congenital cardiac surgeons: 87% (114 of 131) before the 2004 transition to 97% (881 of 913) afterward. The Emory Adult Congenital Heart program has undergone significant growth and change, including transition of the surgical component from the pediatric to the adult facility. While numerous obstacles have been overcome and great progress has been made, additional challenges remain. Copyright © 2017 Elsevier Inc. All rights reserved.
Piller, Linda B; Davis, Barry R; Cutler, Jeffrey A; Cushman, William C; Wright, Jackson T; Williamson, Jeff D; Leenen, Frans HH; Einhorn, Paula T; Randall, Otelio S; Golden, John S; Haywood, L Julian
2002-01-01
Background The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive drugs: alpha-adrenergic blocker (doxazosin), ACE-inhibitor (lisinopril), and calcium-channel blocker (amlodipine). Combined cardiovascular disease risk was significantly increased in the doxazosin arm compared to the chlorthalidone arm (RR 1.25; 95% CI, 1.17–1.33; P < .001), with a doubling of heart failure (fatal, hospitalized, or non-hospitalized but treated) (RR 2.04; 95% CI, 1.79–2.32; P < .001). Questions about heart failure diagnostic criteria led to steps to validate these events further. Methods and Results Baseline characteristics (age, race, sex, blood pressure) did not differ significantly between treatment groups (P < .05) for participants with heart failure events. Post-event pharmacologic management was similar in both groups and generally conformed to accepted heart failure therapy. Central review of a small sample of cases showed high adherence to ALLHAT heart failure criteria. Of 105 participants with quantitative ejection fraction measurements provided, (67% by echocardiogram, 31% by catheterization), 29/46 (63%) from the chlorthalidone group and 41/59 (70%) from the doxazosin group were at or below 40%. Two-year heart failure case-fatalities (22% and 19% in the doxazosin and chlorthalidone groups, respectively) were as expected and did not differ significantly (RR 0.96; 95% CI, 0.67–1.38; P = 0.83). Conclusion Results of the validation process supported findings of increased heart failure in the ALLHAT doxazosin treatment arm compared to the chlorthalidone treatment arm. PMID:12459039
Zhang, Hanfei; Goodman, Shaun G; Yan, Raymond T; Steg, Ph Gabriel; Kornder, Jan M; Gyenes, Gabor T; Grondin, Francois R; Brieger, David; DeYoung, J Paul; Gallo, Richard; Yan, Andrew T
2016-06-01
The prognostic significance of prior heart failure in acute coronary syndromes has not been well studied. Accordingly, we evaluated the baseline characteristics, management patterns and clinical outcomes in patients with acute coronary syndromes who had prior heart failure. The study population consisted of acute coronary syndrome patients in the Global Registry of Acute Coronary Events, expanded Global Registry of Acute Coronary Events and Canadian Registry of Acute Coronary Events between 1999 and 2008. Of the 13,937 eligible patients (mean age 66±13 years, 33% female and 28.3% with ST-elevation myocardial infarction), 1498 (10.7%) patients had a history of heart failure. Those with prior heart failure tended to be older, female and had lower systolic blood pressure, higher Killip class and creatinine on presentation. Prior heart failure was also associated with significantly worse left ventricular systolic function and lower rates of cardiac catheterization and coronary revascularization. The group with previous heart failure had significantly higher rates of acute decompensated heart failure, cardiogenic shock, myocardial (re)infarction and mortality in hospital. In multivariable analysis, prior heart failure remained an independent predictor of in-hospital mortality (odds ratio 1.48, 95% confidence interval 1.08-2.03, p=0.015). Prior heart failure was associated with high risk features on presentation and adverse outcomes including higher adjusted in-hospital mortality in acute coronary syndrome patients. However, acute coronary syndrome patients with prior heart failure were less likely to receive evidence-based therapies, suggesting potential opportunities to target more intensive treatment to improve their outcome. © The European Society of Cardiology 2015.
[Study on ultra-structural pathological changes of rats poisoned by tetramine].
Zhi, Chuan-hong; Liu, Liang; Liu, Yan
2005-05-01
To observe ultra-structural pathological changes of materiality viscera of rats poisoned by different dose of tetramine and to study the toxic mechanism. Acute and subacute tetramine toxicity models were made by oral administration with different dose of tetramine. Brain, heart, liver, spleen and kidney were extracted and observed by electromicroscopic examination. The injuries of brain cells, cardiocytes and liver cells were induced by different dose of tetramine. These were not obviously different of the injuries of the kindy cells and spleen cells of rats poisoned by different dose of tetramine. Ultra-structural pathological changes were abserved including mitochondria slight swelling and neurolemma's array turbulence in the brain cells, mitochondria swelling or abolish and rupture of muscle fiber in the heart cells, mitochondria swelling and the glycogen decreased in the liver cells. The toxic target organs of tetramine are the heart, brain and liver.
Wang, Hui-Ping; Zhang, Wen-Hui; Wang, Xiao-Fang; Zhu, Jin; Zheng, Yan-Qian; Xia, Qin; Zhi, Jian-Ming
2014-01-01
Epidemiological studies have demonstrated that women with a history of preeclampsia have a two-fold increased risk of developing cardiovascular diseases in later life. It is not known whether or not this risk is associated with angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of AT1 receptor (AT1R), which is believed to be involved in the pathogenesis of preeclampsia. The objective of the present study was to confirm the hypothesis that AT1-AA exposure during pregnancy may change the maternal cardiac structure and increase the susceptibility of the postpartum heart to ischemia/reperfusion injury (IRI). In the present study, we first established a preeclampsia rat model by intravenous injection of AT1-AA extracted from the plasma of rats immunized with AT1R, observed the susceptibility of the postpartum maternal heart to IRI at 16 weeks postpartum using the Langendorff preparation, and examined the cardiac structure using light and transmission electron microscopy. The modeled animals presented with symptoms very similar to the clinical symptoms of human preeclampsia during pregnancy, including hypertension and proteinuria. The left ventricular weight (LVW) and left ventricular mass index (LVMI) in AT1-AA treatment group were significantly increased as compared with those of the control group (p < 0.01), although there was no significant difference in final weight between the two groups. AT1-AA acting on AT1R not only induced myocardial cell hypertrophy, mitochondrial swelling, cristae disorganization and collagen accumulation in the interstitium but affected the left ventricular (LV) function and delayed recovery from IRI. In contrast, co-treatment with AT1-AA + losartan completely blocked AT1-AA-induced changes in cardiac structure and function. These data indicate that the presence of AT1-AA during pregnancy was strongly associated with the markers of LV geometry changes and remodeling, and increased the cardiac susceptibility to IRI in later life of postpartum maternal rats. PMID:24979132
Wang, Hui-Ping; Zhang, Wen-Hui; Wang, Xiao-Fang; Zhu, Jin; Zheng, Yan-Qian; Xia, Qin; Zhi, Jian-Ming
2014-06-27
Epidemiological studies have demonstrated that women with a history of preeclampsia have a two-fold increased risk of developing cardiovascular diseases in later life. It is not known whether or not this risk is associated with angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of AT1 receptor (AT1R), which is believed to be involved in the pathogenesis of preeclampsia. The objective of the present study was to confirm the hypothesis that AT1-AA exposure during pregnancy may change the maternal cardiac structure and increase the susceptibility of the postpartum heart to ischemia/reperfusion injury (IRI). In the present study, we first established a preeclampsia rat model by intravenous injection of AT1-AA extracted from the plasma of rats immunized with AT1R, observed the susceptibility of the postpartum maternal heart to IRI at 16 weeks postpartum using the Langendorff preparation, and examined the cardiac structure using light and transmission electron microscopy. The modeled animals presented with symptoms very similar to the clinical symptoms of human preeclampsia during pregnancy, including hypertension and proteinuria. The left ventricular weight (LVW) and left ventricular mass index (LVMI) in AT1-AA treatment group were significantly increased as compared with those of the control group (p < 0.01), although there was no significant difference in final weight between the two groups. AT1-AA acting on AT1R not only induced myocardial cell hypertrophy, mitochondrial swelling, cristae disorganization and collagen accumulation in the interstitium but affected the left ventricular (LV) function and delayed recovery from IRI. In contrast, co-treatment with AT1-AA + losartan completely blocked AT1-AA-induced changes in cardiac structure and function. These data indicate that the presence of AT1-AA during pregnancy was strongly associated with the markers of LV geometry changes and remodeling, and increased the cardiac susceptibility to IRI in later life of postpartum maternal rats.
Pfeil, Uwe; Bharathala, Subhashini; Murtaza, Ghulam; Mermer, Petra; Papadakis, Tamara; Boening, Andreas; Kummer, Wolfgang
2016-12-01
Heart valves are highly organized structures determining the direction of blood flow through the heart. Smooth muscle cells within the valve are thought to play an active role during the heart cycle, rather than being just passive flaps. The mature heart valve is composed of extracellular matrix (ECM), various differentiations of valvular interstitial cells (VIC), smooth muscle cells and overlying endothelium. VIC are important for maintaining the structural integrity of the valve, thereby affecting valve function and ECM remodelling. Accumulating evidence suggests an important role of calcitonin receptor-like receptor (CRL) signalling in preventing heart damage under several pathological conditions. Thus we investigate the existence of a putative CRL signalling system in mouse and human heart valves by real-time RT-PCR, laser-assisted microdissection, immunofluorescence and NADPH-diaphorase histochemistry. Mouse and human heart valves expressed mRNAs for the CRL ligands adrenomedullin (AM), adrenomedullin-2 (AM-2) and calcitonin gene-related peptide (CGRP) and for their receptor components, i.e., CRL and receptor-activity-modifying proteins 1-3. Immunofluorescence analysis revealed AM-, AM-2- and CRL-immunolabelling in endothelial cells and VIC, whereas CGRP immunoreactivity was restricted to nerve fibres and some endothelial cells. Nitric oxide synthase activity, as demonstrated by NADPH-diaphorase histochemistry, was shown mainly in valvular endothelial cells in mice, whereas in human aortic valves, VIC and smooth muscle cells were positive. Our results showed the presence of an intrinsic AM/AM-2/CGRP signalling system in murine and human heart valves with distinct cellular localization, suggesting its involvement in the regulation of valve stiffness and ECM production and turnover.
NASA Astrophysics Data System (ADS)
Heineman, K. D.; Russo, S. E.; Baillie, I. C.; Mamit, J. D.; Chai, P. P.-K.; Chai, L.; Hindley, E. W.; Lau, B.-T.; Tan, S.; Ashton, P. S.
2015-05-01
Fungal decay of heartwood creates hollows and areas of reduced wood density within the stems of living trees known as heart rot. Although heart rot is acknowledged as a source of error in forest aboveground biomass estimates, there are few datasets available to evaluate the environmental controls over heart rot infection and severity in tropical forests. Using legacy and recent data from drilled, felled, and cored stems in mixed dipterocarp forests in Sarawak, Malaysian Borneo, we quantified the frequency and severity of heart rot, and used generalized linear mixed effect models to characterize the association of heart rot with tree size, wood density, taxonomy, and edaphic conditions. Heart rot was detected in 55% of felled stems > 30 cm DBH, while the detection frequency was lower for stems of the same size evaluated by non-destructive drilling (45%) and coring (23%) methods. Heart rot severity, defined as the percent stem volume lost in infected stems, ranged widely from 0.1-82.8%. Tree taxonomy explained the greatest proportion of variance in heart rot frequency and severity among the fixed and random effects evaluated in our models. Heart rot frequency, but not severity, increased sharply with tree diameter, ranging from 56% infection across all datasets in stems > 50 cm DBH to 11% in trees 10-30 cm DBH. The frequency and severity of heart rot increased significantly in soils with low pH and cation concentrations in topsoil, and heart rot was more common in tree species associated with dystrophic sandy soils than with nutrient-rich clays. When scaled to forest stands, the percent of stem biomass lost to heart rot varied significantly with soil properties, and we estimate that 7% of the forest biomass is in some stage of heart rot decay. This study demonstrates not only that heart rot is a significant source of error in forest carbon estimates, but also that it strongly covaries with soil resources, underscoring the need to account for edaphic variation in estimating carbon storage in tropical forests.
Gu, Lianzhi; Pandey, Vikas; Geenen, David L.; Chowdhury, Shamim A. K.; Piano, Mariann R.
2008-01-01
Aim To determine the effects of cigarette smoke (CS) exposure on the expression/activation of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated kinase [ERK1/2], p38-kinase [p38] and c-Jun NH2–terminal protein kinase [JNK]), norepinephrine (NE) levels and myocardial structure and function. Methods Rats were randomised to two groups: CS–exposed (n = 10) or room air (CON) (n = 12). After 5 weeks, the animals underwent echocardiography with pulse-wave Doppler flow measurements. Hearts were removed for microscopy and Western blot analysis. Results CS exposure was associated with significant increases in NE urinary levels and larger ventricular dimensions (mm) (CON = left ventricular end diastolic dimension [LVEDD] 7.99 ± 0.10, LV end systolic dimension [LVESD] 4.55 ± 0.20, CS = LVEDD 8.3 ± 0.10, LVESD 5.3 ± 0.09, p = 0.026, p = 0.003). There was also evidence of systolic dysfunction in the CS-exposed group compared to the CON group (fractional shortening %, CON = 43 ± 2, CS = 36 ± .09, p = 0.010). In CS-exposed hearts, significant increases in phosphorylated p38/total p38 (0.975 ± 0.05) and phosphorylated ERK1/2/totalERK1/2 (1.919 ± 0.050) were found compared to CON hearts (0.464 ± 0.008, 0.459 ± 0.050, respectively). No significant differences were found in JNK levels between the groups. Conclusions Increased NE levels and MAPK activation are associated with CS-related left ventricular remodelling. PMID:18815071
Kilinc, Ozden; Cincin, Altug; Pehlivan, Aslihan; Midi, Ipek; Kepez, Alper; Agan, Kadriye
2016-06-01
Epilepsy is a disease known to occur with autonomous phenomenons. Earlier studies indicate decreased heart rate variability (HRV) during ictal and interictal periods among epilepsy patients. In this study, we aim to investigate cardiac rhythm abnormalities and HRV during interictal period between drug-naïve patients with idiopathic generalized epilepsy (IGE) and healthy control group. Twenty-six patients with IGE and 26 healthy individuals included in the study. In order to eliminate any structural cardiac pathology, transthoracic echocardiography was performed in all subjects and time and frequency domain parameters of HRV were evaluated after 24-hour rhythm holter monitoring. Between two groups, no significant difference was detected in terms of mean heart rate and maximum duration between the start of the Q waves and the end of the T waves (QT intervals). In the time domain analysis of HRV, no statically significant difference was detected for standard deviation of all R - R intervals and root-mean-square of successive differences between patient and control group (p = 0,070 and p = 0,104 respectively). In the frequency domain analysis of HRV, patients tended to display lower total power and very low frequency power than did healthy subjects, but the differences were not statistically significant. Our results suggest that there is no major effect of the epilepsy on HRV in patients with IGE. It should be emphasized that, in this study, HRV was evaluated only in patients with IGE and that the results are not proper to be generalized for patients with partial seizures.
Hyde, Annastasia S.; Farmer, Erin L.; Easley, Katherine E.; van Lammeren, Kristy; Christoffels, Vincent M.; Barycki, Joseph J.; Bakkers, Jeroen; Simpson, Melanie A.
2012-01-01
Cardiac valve defects are a common congenital heart malformation and a significant clinical problem. Defining molecular factors in cardiac valve development has facilitated identification of underlying causes of valve malformation. Gene disruption in zebrafish revealed a critical role for UDP-glucose dehydrogenase (UGDH) in valve development, so this gene was screened for polymorphisms in a patient population suffering from cardiac valve defects. Two genetic substitutions were identified and predicted to encode missense mutations of arginine 141 to cysteine and glutamate 416 to aspartate, respectively. Using a zebrafish model of defective heart valve formation caused by morpholino oligonucleotide knockdown of UGDH, transcripts encoding the UGDH R141C or E416D mutant enzymes were unable to restore cardiac valve formation and could only partially rescue cardiac edema. Characterization of the mutant recombinant enzymes purified from Escherichia coli revealed modest alterations in the enzymatic activity of the mutants and a significant reduction in the half-life of enzyme activity at 37 °C. This reduction in activity could be propagated to the wild-type enzyme in a 1:1 mixed reaction. Furthermore, the quaternary structure of both mutants, normally hexameric, was destabilized to favor the dimeric species, and the intrinsic thermal stability of the R141C mutant was highly compromised. The results are consistent with the reduced function of both missense mutations significantly reducing the ability of UGDH to provide precursors for cardiac cushion formation, which is essential to subsequent valve formation. The identification of these polymorphisms in patient populations will help identify families genetically at risk for valve defects. PMID:22815472
Del Gaudio, Costantino; Gasbarroni, Pier Luca; Romano, Giovanni Paolo
2016-12-01
End-stage failing heart valves are currently replaced by mechanical or biological prostheses. Both types positively contribute to restore the physiological function of native valves, but a number of drawbacks limits the expected performances. In order to improve the outcome, tissue engineering can offer an alternative approach to design and fabricate innovative heart valves capable to support the requested function and to promote the formation of a novel, viable and correctly operating physiological structure. This potential result is particularly critical if referred to the aortic valve, being the one mainly exposed to structural and functional degeneration. In this regard, the here proposed study presents the fabrication and in vitro characterization of a bioresorbable electrospun heart valve prosthesis using the particle image velocimetry technique either in physiological and pathological fluid dynamic conditions. The scaffold was designed to reproduce the aortic valve geometry, also mimicking the fibrous structure of the natural extracellular matrix. To evaluate its performances for possible implantation, the flow fields downstream the valve were accurately investigated and compared. The experimental results showed a correct functionality of the device, supported by the formation of vortex structures at the edge of the three cusps, with Reynolds stress values below the threshold for the risk of hemolysis (which can be comprised in the range 400-4000N/m(2) depending on the exposure period), and a good structural resistance to the mechanical loads generated by the driving pressure difference. Copyright © 2016 Elsevier Ltd. All rights reserved.
Rong, Xiaoshan; Peng, Youqing; Yu, Hai-Ping; Li, Dan
2017-03-01
To explore the cultural factors related to dietary and fluid restriction behaviours among older Chinese patients. Excess dietary sodium and fluid intake are risk factors contributing to the worsening and rehospitalisation for heart failure in older patients. Managing the complex fluid and diet requirements of heart failure patients is challenging and is made more complicated by cultural variations in self-management behaviours in response to a health threat. Qualitative study using semi-structured in interviews and framework analysis. The design of this study is qualitative descriptive. Semi-structured in-depth interviews were conducted with 15 heart failure patients. Data were analysed through content analysis. Seven cultural themes emerged from the qualitative data: the values placed on health and illness, customary way of life, preference for folk care and the Chinese healthcare system, and factors related to kinship and social ties, religion, economics and education. Dietary change and management in response to illness, including heart failure, is closely related to individuals' cultural background. Healthcare providers should have a good understanding of cultural aspects that can influence patients' conformity to medical recommendations. Heart failure patients need support that considers their cultural needs. Healthcare providers must have a good understanding of the experiences of people from diverse cultural backgrounds. © 2016 John Wiley & Sons Ltd.
Tsoutsman, Tatiana; Wang, Xiaoyu; Garchow, Kendra; Riser, Bruce; Twigg, Stephen; Semsarian, Christopher
2013-09-01
Hypertrophic cardiomyopathy (HCM) is the most common inherited primary myocardial disorder. HCM is characterized by interstitial fibrosis and excessive accumulation of extracellular matrix (ECM) proteins. Fibrosis in HCM has been associated with impaired cardiac function and heart failure, and has been considered a key substrate for ventricular arrhythmias and sudden death. The molecular triggers underpinning ECM production are not well established. We have previously developed a double-mutant mouse model of HCM that recapitulates the phenotype seen in humans with multiple mutations, including earlier onset of the disease, progression to a dilated phenotype, severe heart failure and premature mortality. The present study investigated the expression of ECM-encoding genes in severe HCM and heart failure. Significant upregulation of structural Fn1, regulatory Mmp14, Timp1, Serpin3A, SerpinE1, SerpineE2, Tgfβ1, and Tgfβ2; and matricellular Ccn2, Postn, Spp1, Thbs1, Thbs4, and Tnc was evident from the early, pre-phenotype stage. Non-myocytes expressed ECM genes at higher levels than cardiomyocytes in normal and diseased hearts. Synchronous increase of secreted CCN2 and TIMP1 plasma levels and decrease of MMP3 levels were observed in end-stage disease. CCN2 protein expression was increased from early disease in double-mutant hearts and played an important role in ECM responses. It was a powerful modulator of ECM regulatory (Timp1 and SerpinE1) and matricellular protein-encoding (Spp1, Thbs1, Thbs4 and Tnc) gene expression in cardiomyocytes when added exogenously in vitro. Modulation of CCN2 (CTGF, connective tissue growth factor) and associated early ECM changes may represent a new therapeutic target in the treatment and prevention of heart failure in HCM. Copyright © 2013 Elsevier Ltd. All rights reserved.
Correlations of chemokine CXCL16 and TNF-α with coronary atherosclerotic heart disease.
Xing, Jieyong; Liu, Yanshao; Chen, Tao
2018-01-01
This study determined the correlations of CXC ligand 16 (CXCL16) and tumor necrosis factor-α (TNF-α) levels with coronary atherosclerotic heart disease (CAHD) and screened for new clinical markers for the prognosis and treatment of the disease. Eighty patients with coronary heart disease and 50 healthy subjects were enrolled into a CAHD or healthy control group, respectively. Computed tomography (CT) coronary angiography and Gensini integral were used to classify plaques and evaluate patients with coronary heart disease. The serum levels of CXCL16 and TNF-α of subjects in each group were detected by enzyme-linked immunosorbent assays (ELISA), and the correlation between levels and clinical markers (such as blood pressure, glucose, lipid and heart rate) and the severity of disease were analyzed. Our results showed the serum levels of CXCL16 and TNF-α were significantly higher in the CAHD group than those in the CK group. The serum CXCL16 levels of the CAHD group patients with plaques were distinctly higher than those of the CADH group patients without plaques, but there were no significant difference in serum TNF-α levels between these two groups of patients. The level of CXCL16 had a significantly positive correlation with the severity of disease, but there was no significant correlation between TNF-α level and the severity of disease. Also, there was no significant correlation between the CXCL16 levels and blood pressure, blood glucose, heart rate, total cholesterol, triglyceride or high-density lipoprotein cholesterol, but there was a clear correlation with the low-density lipoprotein cholesterol. Finally no significant correlations were found between TNF-α levels and each of the clinical markers studied. Based on our findings, the levels of CXCL16 and TNF-α in the patients with coronary heart disease were abnormally increased and the level of CXCL16 correlated closely with the severity of disease. These markers seem to be reliable biological markers for prognosis and disease evaluation in coronary heart disease patients.
NASA Astrophysics Data System (ADS)
Sonntag, Simon J.; Kaufmann, Tim A. S.; Büsen, Martin R.; Laumen, Marco; Linde, Torsten; Schmitz-Rode, Thomas; Steinseifer, Ulrich
2013-04-01
Heart disease is one of the leading causes of death in the world. Due to a shortage in donor organs artificial hearts can be a bridge to transplantation or even serve as a destination therapy for patients with terminal heart insufficiency. A pusher plate driven pulsatile membrane pump, the Total Artificial Heart (TAH) ReinHeart, is currently under development at the Institute of Applied Medical Engineering of RWTH Aachen University.This paper presents the methodology of a fully coupled three-dimensional time-dependent Fluid Structure Interaction (FSI) simulation of the TAH using a commercial partitioned block-Gauss-Seidel coupling package. Partitioned coupling of the incompressible fluid with the slender flexible membrane as well as a high fluid/structure density ratio of about unity led inherently to a deterioration of the stability (‘artificial added mass instability’). The objective was to conduct a stable simulation with high accuracy of the pumping process. In order to achieve stability, a combined resistance and pressure outlet boundary condition as well as the interface artificial compressibility method was applied. An analysis of the contact algorithm and turbulence condition is presented. Independence tests are performed for the structural and the fluid mesh, the time step size and the number of pulse cycles. Because of the large deformation of the fluid domain, a variable mesh stiffness depending on certain mesh properties was specified for the fluid elements. Adaptive remeshing was avoided. Different approaches for the mesh stiffness function are compared with respect to convergence, preservation of mesh topology and mesh quality. The resulting mesh aspect ratios, mesh expansion factors and mesh orthogonalities are evaluated in detail. The membrane motion and flow distribution of the coupled simulations are compared with a top-view recording and stereo Particle Image Velocimetry (PIV) measurements, respectively, of the actual pump.
Effects of head-down bed rest on complex heart rate variability: Response to LBNP testing
NASA Technical Reports Server (NTRS)
Goldberger, Ary L.; Mietus, Joseph E.; Rigney, David R.; Wood, Margie L.; Fortney, Suzanne M.
1994-01-01
Head-down bed rest is used to model physiological changes during spaceflight. We postulated that bed rest would decrease the degree of complex physiological heart rate variability. We analyzed continuous heart rate data from digitized Holter recordings in eight healthy female volunteers (age 28-34 yr) who underwent a 13-day 6 deg head-down bed rest study with serial lower body negative pressure (LBNP) trials. Heart rate variability was measured on a 4-min data sets using conventional time and frequency domain measures as well as with a new measure of signal 'complexity' (approximate entropy). Data were obtained pre-bed rest (control), during bed rest (day 4 and day 9 or 11), and 2 days post-bed rest (recovery). Tolerance to LBNP was significantly reduced on both bed rest days vs. pre-bed rest. Heart rate variability was assessed at peak LBNP. Heart rate approximate entropy was significantly decreased at day 4 and day 9 or 11, returning toward normal during recovery. Heart rate standard deviation and the ratio of high- to low-power frequency did not change significantly. We conclude that short-term bed rest is associated with a decrease in the complex variability of heart rate during LBNP testing in healthy young adult women. Measurement of heart rate complexity, using a method derived from nonlinear dynamics ('chaos theory'), may provide a sensitive marker of this loss of physiological variability, complementing conventional time and frequency domain statistical measures.
Waninge, Aly; van der Putten, Annette A J; Stewart, Roy E; Steenbergen, Bert; van Wijck, Ruud; van der Schans, Cees P
2013-11-01
Because physical fitness and health are related to physical activity, it is important to gain an insight into the physical activity levels of persons with profound intellectual and multiple disabilities (PIMD). The purpose of this study was to examine heart rate patterns to measure the activity levels of persons with PIMD and to analyze these heart rate patterns according to participant characteristics, observed level of activity, days, and time of day. The heart rate patterns of 24 participants with PIMD were measured continuously using a heart rate monitor for 8 h · d for a period of 6 days. Physical activity levels were measured with questionnaires. Data were analyzed using multilevel analysis. The results indicate that the participants use only 32% of their heart rate reserve over 6 days. The intensity of heart rate reserve ranged from 1 to 62%. On a given day, wide ranges in heart rates between participants and within persons were observed. Between days, only small ranges in the heart rate were found. The participants could be grouped into 4 classes according to their heart rate. In addition, factors such as time of day, physical activity, and age are significantly related to heart rate patterns. In conclusion, this study is an important first step in exploring activity patterns based on heart rate patterns in persons with PIMD. The participants used relatively small fractions of their heart rate reserves. Time of day and age appear to have a considerable influence on heart rate patterns. The observed classes in heart rate patterns suggest that other probably more personal and psychosocial factors have significant influences on heart rate patterns, as well.
Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.
Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying
2015-07-01
The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.
How heart rate variability affects emotion regulation brain networks.
Mather, Mara; Thayer, Julian
2018-02-01
Individuals with high heart rate variability tend to have better emotional well-being than those with low heart rate variability, but the mechanisms of this association are not yet clear. In this paper, we propose the novel hypothesis that by inducing oscillatory activity in the brain, high amplitude oscillations in heart rate enhance functional connectivity in brain networks associated with emotion regulation. Recent studies using daily biofeedback sessions to increase the amplitude of heart rate oscillations suggest that high amplitude physiological oscillations have a causal impact on emotional well-being. Because blood flow timing helps determine brain network structure and function, slow oscillations in heart rate have the potential to strengthen brain network dynamics, especially in medial prefrontal regulatory regions that are particularly sensitive to physiological oscillations.
Alsaleh, Eman; Blake, Holly; Windle, Richard
2012-12-01
Although physical activity has significant health benefits in the treatment of patients with coronary heart disease, patients often do not follow prescribed physical activity recommendations. Behavioural strategies have been shown to be efficacious in increasing physical activity among those patients with coronary heart disease who are attending structured cardiac rehabilitation programmes. Research has also shown that tailoring consultation according to patients' needs and sending motivational reminders are successful ways of motivating patients to be physically active. However, there is a lack of evidence for the efficacy of behavioural interventions based on individualised consultation in promoting physical activity among those patients with coronary heart disease who are not attending structured physical activity programmes. This paper outlines the study protocol for a trial which is currently underway, to examine the effect of a behavioural change intervention delivered through individualised consultation calls and motivational reminder text messages on the level of physical activity among patients with coronary heart disease. Two large hospitals in Jordan. Eligible patients aged between 18 and 70 years, who are clinically stable, are able to perform physical activity and who have access to a mobile telephone have been randomly allocated to control or intervention group. Two-group randomised controlled trial. Behavioural intervention will be compared with usual care in increasing physical activity levels among patients with coronary heart disease. The control group (n=85) will receive advice from their doctors about physical activity as they would in usual practice. The intervention group (n=71) will receive the same advice, but will also receive behavioural change intervention (goal-setting, feed-back, self-monitoring) that will be delivered over a period of six months. Intervention will be delivered through individually tailored face-to-face and telephone consultations, supported by motivational SMS text messages to encourage and remind patients to attain these goals. The participants and the researcher delivering the intervention are not blinded to group assignment. Recruitment started in February 2012 and preliminary findings are expected in November 2012. It is hypothesised that behavioural intervention delivered through tailored individualised consultation supported by motivational SMS text message reminders will help CHD patients to increase their level of PA. The study is registered as a clinical trial at ISRCTN register (ISRCTN48570595). Copyright © 2012 Elsevier Ltd. All rights reserved.
[Effects of low-dose insulin on oxidation-reduction in rat organs after major burns].
Wang, Wei; Jiang, Hong-mei; Li, Wei-ren; Zuo, Lu; Tao, Lei; Yu, Xiang
2013-11-12
To explore the effects of low-dose insulin on oxidation-reduction of heart and kidney in rats immediately after severe burns. Twenty four male Sprague-Dawley (SD) rats were randomly divided into 3 groups of sham burn, burn and treatment (n = 8 each). The sham burn group was placed into 37 °C warm water for 15 seconds to simulate burn process and received no fluid replacement. The burn and treatment groups were immersed into (95 ± 0.5) °C hot water for 15 seconds to make a rat model of 30% total burn surface area, III degree burn injury and immediately received an intraperitoneal injection of physiological saline (40 ml/kg). At the same time, a subcutaneous injection of insulin (1.0 U×kg(-1)×d(-1)) was given in the treatment group and a subcutaneous injection of same-volume physiological saline in the burn group. The rats were sacrificed after 24 post-scald hours (PSH). Abdominal aortic blood was collected for an analysis of blood glucose. The oxidation and antioxidation parameters of heart and kidney, such as malondialdehyde (MDA), xanthine oxidase (XO), myeloperoxidase (MPO), total superoxide dismutase (T-SOD), superoxide dismutase 1, 2 (SOD1, 2), catalase (CAT) and glutathione peroxidase (GPx), were detected by spectrophotometry. Compared with the sham burn group, MDA content, XO and MPO activities of heart and kidney were significantly higher in the burn group (all P < 0.05); in the treatment group, MDA content and XO activity of heart were significantly lower than the burn group ((0.85 ± 0.07) vs (1.11 ± 0.07) nmol/mg, (69.72 ± 1.94) vs (77.21 ± 2.10) U/g) while the MPO activities of heart and kidney were significantly lower (all P < 0.05).compared with the sham burn group, the activities of T-SOD, CAT, GPx of heart and kidney were significantly lower in the burn group, SOD1 activity of kidney was significantly lower, but SOD2 activity of kidney was significantly higher while SOD2 activity of heart was significantly lower (all P < 0.05); Compared with the burn group, the activities of T-SOD and SOD1 of heart in the treatment group were significantly higher ((83.5 ± 2.5) vs (79.6 ± 3.2), (62.8 ± 2.3) vs (58.8 ± 3.0) U/mg), CAT and GPx activity of heart and kidney were significantly higher (all P < 0.05). Compared with the sham burn group, blood glucose in the burn and treatment group were significantly higher ((7.81 ± 0.30), (7.19 ± 0.22) vs (6.30 ± 0.24) mmol/L) and blood glucose in the treatment group was significantly lower than the burn group((7.81 ± 0.30) mmol/L)(all P < 0.05). During an early stage, a low-dose insulin may intervene in heart tissue lipid peroxidation of severely burned rats. And differences exist in the effects of oxidation-reduction between heart and kidney.
A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure.
Keith, M E; Jeejeebhoy, K N; Langer, A; Kurian, R; Barr, A; O'Kelly, B; Sole, M J
2001-02-01
Oxidative stress is increased in patients with congestive heart failure and can contribute to the progressive deterioration observed in these patients. Increased oxidative stress is the result of either an increased production of free radicals or a depletion of endogenous antioxidants, such as vitamin E. We aimed to determine whether vitamin E supplementation of patients with advanced heart failure would modify levels of oxidative stress, thereby preventing or delaying the deterioration associated with free radical injury. Fifty-six outpatients with advanced heart failure (New York Heart Association functional class III or IV) were enrolled in a double-blind randomized controlled trial for 12 wk. At a baseline visit and at 2 follow-up visits, blood and breath samples were collected for the measurement of indexes of heart function and disease state, including malondialdehyde, isoprostanes, and breath pentane and ethane. Quality of life was also assessed at baseline and after 12 wk of treatment. Vitamin E treatment significantly increased plasma concentrations of alpha-tocopherol in the treatment group but failed to significantly affect any other marker of oxidative stress or quality of life. In addition, concentrations of atrial natriuretic peptide (a humoral marker of ventricular dysfunction), neurohormonal-cytokine markers of prognosis, tumor necrosis factor, epinephrine, and norepinephrine were unchanged with treatment and were not significantly different from those in the control group. Supplementation with vitamin E did not result in any significant improvements in prognostic or functional indexes of heart failure or in the quality of life of patients with advanced heart failure.
Maternal obesity and congenital heart defects: a population-based study123
Mills, James L; Troendle, James; Conley, Mary R; Carter, Tonia; Druschel, Charlotte M
2010-01-01
Background: Obesity affects almost one-third of pregnant women and causes many complications, including neural tube defects. It is not clear whether the risk of congenital heart defects, the most common malformations, is also increased. Objective: This study was conducted to determine whether obesity is associated with an increased risk of congenital heart defects. Design: A population-based, nested, case-control study was conducted in infants born with congenital heart defects and unaffected controls from the cohort of all births (n = 1,536,828) between 1993 and 2003 in New York State, excluding New York City. The type of congenital heart defect, maternal body mass index (BMI; in kg/m2), and other risk factors were obtained from the Congenital Malformations Registry and vital records. Mothers of 7392 congenital heart defect cases and 56,304 unaffected controls were studied. Results: All obese women (BMI ≥ 30) were significantly more likely than normal-weight women (BMI: 19–24.9) to have children with a congenital heart defect [odds ratio (OR): 1.15; 95% CI: 1.07, 1.23; P < 0.0001]. Overweight women were not at increased risk (OR: 1.00; 95% CI: 0.94, 1.06). The risk in morbidly obese women (BMI ≥ 40) was higher (OR: 1.33; 95% CI: 1.15, 1.54; P = 0.0001) than that in obese women with a BMI of 30–39.9 (OR: 1.11; 95% CI: 1.04, 1.20; P = 0.004). There was a highly significant trend of increasing OR for congenital heart defects with increasing maternal obesity (P < 0.0001). The offspring of obese women had significantly higher ORs for atrial septal defects, hypoplastic left heart syndrome, aortic stenosis, pulmonic stenosis, and tetralogy of Fallot. Conclusions: Obese, but not overweight, women are at significantly increased risk of bearing children with a range of congenital heart defects, and the risk increases with increasing BMI. Weight reduction as a way to reduce risk should be investigated. PMID:20375192
Probing the Electrophysiology of the Developing Heart
Watanabe, Michiko; Rollins, Andrew M.; Polo-Parada, Luis; Ma, Pei; Gu, Shi; Jenkins, Michael W.
2016-01-01
Many diseases that result in dysfunction and dysmorphology of the heart originate in the embryo. However, the embryonic heart presents a challenging subject for study: especially challenging is its electrophysiology. Electrophysiological maturation of the embryonic heart without disturbing its physiological function requires the creation and deployment of novel technologies along with the use of classical techniques on a range of animal models. Each tool has its strengths and limitations and has contributed to making key discoveries to expand our understanding of cardiac development. Further progress in understanding the mechanisms that regulate the normal and abnormal development of the electrophysiology of the heart requires integration of this functional information with the more extensively elucidated structural and molecular changes. PMID:29367561
Knitting for heart valve tissue engineering
Ayad, Nadia; Wojciechowska, Dorota; Zielińska, Dorota; Struszczyk, Marcin H.; Latif, Najma; Yacoub, Magdi
Knitting is a versatile technology which offers a large portfolio of products and solutions of interest in heart valve (HV) tissue engineering (TE). One of the main advantages of knitting is its ability to construct complex shapes and structures by precisely assembling the yarns in the desired position. With this in mind, knitting could be employed to construct a HV scaffold that closely resembles the authentic valve. This has the potential to reproduce the anisotropic structure that is characteristic of the heart valve with the yarns, in particular the 3-layered architecture of the leaflets. These yarns can provide oriented growth of cells lengthwise and consequently enable the deposition of extracellular matrix (ECM) proteins in an oriented manner. This technique, therefore, has a potential to provide a functional knitted scaffold, but to achieve that textile engineers need to gain a basic understanding of structural and mechanical aspects of the heart valve and in addition, tissue engineers must acquire the knowledge of tools and capacities that are essential in knitting technology. The aim of this review is to provide a platform to consolidate these two fields as well as to enable an efficient communication and cooperation among these two research areas. PMID:29043276
[3H]-nitrendipine binding in membranes obtained from hypoxic and reoxygenated heart.
Matucci, R; Bennardini, F; Sciammarella, M L; Baccaro, C; Stendardi, I; Franconi, F; Giotti, A
1987-04-01
We compared the binding properties of [3H]-nitrendipine in heart membranes from normal guinea-pig heart and from hypoxic or hypoxic and reoxygenated heart. The [3H]-nitrendipine binds a single class of high capacity (Bmax 667.2 +/- 105.2) with high affinity (KD 0.14 +/- 0.02) binding sites. By contrast, in membranes of hypoxic and reoxygenated heart the Bmax decreases significantly while it remains unaffected during hypoxia. Xanthinoxidase activity is increased in hypoxic-reoxygenated hearts.
Ecstasy produces left ventricular dysfunction and oxidative stress in rats
Shenouda, Sylvia K.; Lord, Kevin C.; McIlwain, Elizabeth; Lucchesi, Pamela A.; Varner, Kurt J.
2008-01-01
Aims Our aim was to determine whether the repeated, binge administration of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) produces structural and/or functional changes in the myocardium that are associated with oxidative stress. Methods and results Echocardiography and pressure–volume conductance catheters were used to assess left ventricular (LV) structure and function in rats subjected to four ecstasy binges (9 mg/kg i.v. for 4 days, separated by a 10 day drug-free period). Hearts from treated and control rats were used for either biochemical and proteomic analysis or the isolation of adult LV myocytes. After the fourth binge, treated hearts showed eccentric LV dilation and diastolic dysfunction. Systolic function was not altered in vivo; however, the magnitude of the contractile responses to electrical stimulation was significantly smaller in myocytes from rats treated in vivo with ecstasy compared with myocytes from control rats. The magnitude of the peak increase in intracellular calcium (measured by Fura-2) was also significantly smaller in myocytes from ecstasy-treated vs. control rats. The relaxation kinetics of the intracellular calcium transients were significantly longer in myocytes from ecstasy-treated rats. Ecstasy significantly increased nitrotyrosine content in the left ventricle. Proteomic analysis revealed increased nitration of contractile proteins (troponin-T, tropomyosin alpha-1 chain, myosin light polypeptide, and myosin regulatory light chain), mitochondrial proteins (Ub-cytochrome-c reductase and ATP synthase), and sarcoplasmic reticulum calcium ATPase. Conclusion The repeated binge administration of ecstasy produces eccentric LV dilation and dysfunction that is accompanied by oxidative stress. These functional responses may result from the redox modification of proteins involved in excitation-contraction coupling and/or mitochondrial energy production. Together, these results indicate that ecstasy has the potential to produce serious cardiac toxicity and ventricular dysfunction. PMID:18495670
Arai, Kaori; Nakagawa, Yui; Iwata, Toyoto; Horiguchi, Hyogo; Murata, Katsuyuki
2013-01-01
To clarify the links between ECG QT-related parameters and heart rate variability (HRV) and the covariates possibly distorting them, the averaged RR and QT intervals in a single lead ECG were measured for 64 male and 86 female subjects aged 18-26. The QT index, defined by Rautaharju et al., in the young adults was not significantly related to any HRV parameters nor heart rate, but the Bazett's corrected QT (QTc) interval was associated negatively with the parasympathetic activity and positively with heart rate. No significant differences in the QTc interval, QT index or heart rate were seen between the men and women, but they significantly differed between both sexes after adjustment for possible covariates such as age and body mass index (BMI). Significant sex differences in parasympathetic parameters of the HRV were unchanged before and after the adjustment, but significant differences observed in the unadjusted sympathetic parameters disappeared after adjusting for covariates. Age, BMI and body fat percentage also were significant covariates affecting these ECG parameters. Consequently, QT index, unaffected by heart rate and HRV parameters, appears to be a more useful indicator than the QTc interval. Instead, the QT index and HRV parameters are recommended to be simultaneously measured in epidemiological research because they are probably complementary in assessing autonomic nervous function. Also, these parameters should be analyzed in men and women separately. Copyright © 2012 Elsevier B.V. All rights reserved.
Plymale, Jennifer M; Frommelt, Peter C; Nugent, Melodee; Simpson, Pippa; Tweddell, James S; Shillingford, Amanda J
2017-08-01
In infants with aortic arch hypoplasia and small left-sided cardiac structures, successful biventricular repair is dependent on the adequacy of the left-sided structures. Defining accurate thresholds of echocardiographic indices predictive of successful biventricular repair is paramount to achieving optimal outcomes. We sought to identify pre-operative echocardiographic indices of left heart size that predict intervention-free survival in infants with small left heart structures undergoing primary aortic arch repair to establish biventricular circulation (BVC). Infants ≤2 months undergoing aortic arch repair from 1999 to 2010 with aortic and/or mitral valve hypoplasia, (Z-score ≤-2) were included. Pre-operative and follow-up echocardiograms were reviewed. Primary outcome was successful biventricular circulation (BVC), defined as freedom from death, transplant, or single ventricular conversion at 1 year. Need for catheter based or surgical re-intervention (RI), valve annular growth, and significant late aortic or mitral valve obstruction were additional outcomes. Fifty one of 73 subjects (79%) had successful BVC and were free of RI at 1 year. Seven subjects failed BVC; four of those died. The overall 1 year survival for the cohort was 95%. Fifteen subjects underwent a RI but maintained BVC. In univariate analysis, larger transverse aorta (p = 0.006) and aortic valve (p = 0.02) predicted successful BVC without RI. In CART analysis, the combination of mitral valve (MV) to tricuspid valve (TV) ratio ≤0.66 with an aortic valve (AV) annulus Z-score ≤-3 had the greatest power to predict BVC failure (sensitivity 71%, specificity 94%). In those with successful BVC, the combination of both AV and MV Z-score ≤-2.5 increased the odds of RI (OR 3.8; CI 1.3-11.4). Follow-up of non-RI subjects revealed improvement in AV and MV Z-score (median AV annulus changed over time from -2.34 to 0.04 (p < 0.001) and MV changed from -2.88 to -1.41 (p < 0.001), but residual mitral valve stenosis and aortic arch obstruction were present in one-third of subjects. In this cohort of infants requiring initial aortic arch repair with concomitant small left heart structures, successful BVC can be predicted from combined echocardiographic indices. In this complex population, 1 year survival is high, but the need for RI and the presence of residual lesions are common.
Dilated Cardiomyopathy Revealing Cushing Disease
Marchand, Lucien; Segrestin, Bérénice; Lapoirie, Marion; Favrel, Véronique; Dementhon, Julie; Jouanneau, Emmanuel; Raverot, Gérald
2015-01-01
Abstract Cardiovascular impairments are frequent in Cushing's syndrome and the hypercortisolism can result in cardiac structural and functional changes that lead in rare cases to dilated cardiomyopathy (DCM). Such cardiac impairment may be reversible in response to a eucortisolaemic state. A 43-year-old man with a medical past of hypertension and history of smoking presented to the emergency department with global heart failure. Coronary angiography showed a significant stenosis of a marginal branch and cardiac MRI revealed a nonischemic DCM. The left ventricular ejection fraction (LVEF) was estimated as 28% to 30%. Clinicobiological features and pituitary imaging pointed toward Cushing's disease and administration of adrenolytic drugs (metyrapone and ketoconazole) was initiated. Despite the normalization of cortisol which had been achieved 2 months later, the patient presented an acute heart failure. A massive mitral regurgitation secondary to posterior papillary muscle rupture was diagnosed as a complication of the occlusion of the marginal branch. After 6 months of optimal pharmacological treatment for systolic heart failure, as well as treatment with inhibitors of steroidogenesis, there was no improvement of LVEF. The percutaneous mitral valve was therefore repaired and a defibrillator implanted. The severity of heart failure contraindicated pituitary surgery and the patient was instead treated by stereotaxic radiotherapy. This is the first case reporting a Cushing's syndrome DCM without improvement of LVEF despite normalization of serum cortisol levels. PMID:26579807
Determinants of the development of mitral regurgitation in pacing-induced heart failure.
Takagaki, Masami; McCarthy, Patrick M; Goormastic, Marlene; Ochiai, Yoshie; Doi, Kazuyoshi; Kopcak, Michael W; Tabata, Tomotsugu; Cardon, Lisa A; Thomas, James D; Fukamachi, Kiyotaka
2003-01-01
The pacing-induced heart failure model provides an opportunity to assess the structural and functional determinants of mitral regurgitation (MR) in dilated cardiomyopathy. This study aimed to evaluate MR to better understand the multitude of factors contributing to its development. Heart failure was induced by rapid ventricular pacing (230 beats/min) in 40 mongrel dogs. Left ventricular (LV) size and MR were evaluated echocardiographically. LV contractility was analyzed using a conductance catheter. MR increased to mild in 12 animals (regurgitant orifice area, 0.06+/-0.05 cm(2)), moderate in 15 (0.14+/-0.07 cm(2)), and severe in 13 (0.34+/-0.16 cm(2)). The grade of MR had an inverse relationships with E(max) (the slope of the end-systolic pressure-volume relationship, p<0.01) and dE/dt (the slope of the maximum rate of change of pressure-end-diastolic volume [V(ED)] relationship, p<0.01) and positive relationships with V(ED) and end-diastolic cross-sectional areas and lengths (p<0.05) by univariate analysis. The dE/dt had an independently significant (p<0.01) relationship by multivariable logistic regression. Many factors influence the development of MR and because of its similarity to the clinical situation, this model can be used to investigate MR and heart failure, as well as new surgical therapies.
Kumar, T Santhosh; Zhou, Si-Yuan; Joshi, Bhalchandra V; Balasubramanian, Ramachandran; Yang, Tiehong; Liang, Bruce T; Jacobson, Kenneth A
2010-03-25
P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C-P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (genetic model of heart failure) compared to vehicle-infused mice (all inactive at the vasodilatory P2Y(1) receptor). Two phosphonates, (1'S,2'R,3'S,4'R,5'S)-4'-(6-amino-2-chloropurin-9-yl)-2',3'-(dihydroxy)-1'-(phosphonomethylene)-bicyclo[3.1.0]hexane, 4 (MRS2775), and its homologue 9 (MRS2935), both 5'-saturated, containing a 2-Cl substitution, improved echocardiography-derived fractional shortening (20.25% and 19.26%, respectively, versus 13.78% in controls), while unsaturated 5'-extended phosphonates, all 2-H analogues, and a CH(3)-phosphonate were inactive. Thus, chronic administration of nucleotidase-resistant phosphonates conferred a beneficial effect, likely via cardiac P2X receptor activation. Thus, we have greatly expanded the range of carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure.
Vaccination and triploidy increase relative heart weight in farmed Atlantic salmon, Salmo salar L.
Fraser, T W K; Mayer, I; Hansen, T; Poppe, T T; Skjaeraasen, J E; Koppang, E O; Fjelldal, P G
2015-02-01
Heart morphology is particularly plastic in teleosts and differs between farmed and wild Atlantic salmon. However, little is known about how different culture practices and sex affect heart morphology. This study investigated how vaccination, triploidy and sex affected heart size and heart morphology (ventricle shape, angle of the bulbus arteriosus) in farmed Atlantic salmon for 18 months following vaccination (from c. 50-3000 g body weight). In addition, hearts were examined histologically after 7 months in sea water. All fish sampled were sexually immature. Vaccinated fish had significantly heavier hearts relative to body weight and a more triangular ventricle than unvaccinated fish, suggesting a greater cardiac workload. Irrespective of time, triploids had significantly heavier hearts relative to body weight, a more acute angle of the bulbus arteriosus and less fat deposition in the epicardium than diploids. The ventricle was also more triangular in triploids than diploids at seawater transfer. Sex had transient effects on the angle of the bulbus arteriosus, but no effect on relative heart weight or ventricle shape. From a morphological perspective, the results indicate that vaccination and triploidy increase cardiac workload in farmed Atlantic salmon. © 2014 John Wiley & Sons Ltd.
Margulies, Kenneth B.; Hernandez, Adrian F.; Redfield, Margaret M.; Givertz, Michael M.; Oliveira, Guilherme H.; Cole, Robert; Mann, Douglas L.; Whellan, David J.; Kiernan, Michael S.; Felker, G. Michael; McNulty, Steven E.; Anstrom, Kevin J.; Shah, Monica R.; Braunwald, Eugene; Cappola, Thomas P.
2016-01-01
IMPORTANCE Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status. OBJECTIVE To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. DESIGN, SETTING, AND PARTICIPANTS Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized. Patients were enrolled between August 2013 and March 2015 at 24 US sites. INTERVENTIONS The GLP-1 agonist liraglutide (n = 154) or placebo (n = 146) via a daily subcutaneous injection; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days. MAIN OUTCOMES AND MEASURES The primary end point was a global rank score in which all patients, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days. Higher values indicate better health (stability). Exploratory secondary outcomes included primary end point components, cardiac structure and function, 6-minute walk distance, quality of life, and combined events. RESULTS Among the 300 patients who were randomized (median age, 61 years [interquartile range {IQR}, 52–68 years]; 64 [21%] women; 178 [59%] with type 2 diabetes; median LVEF of 25% [IQR, 19%–33%]; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [IQR, 1054–4235 pg/mL]), 271 completed the study. Compared with placebo, liraglutide had no significant effect on the primary end point (mean rank of 146 for the liraglutide group vs 156 for the placebo group, P = .31). There were no significant between-group differences in the number of deaths (19 [12%] in the liraglutide group vs 16 [11%] in the placebo group; hazard ratio, 1.10 [95% CI, 0.57–2.14]; P = .78) or rehospitalizations for heart failure (63 [41%] vs 50 [34%], respectively; hazard ratio, 1.30 [95% CI, 0.89–1.88]; P = .17) or for the exploratory secondary end points. Prespecified subgroup analyses in patients with diabetes did not reveal any significant between-group differences. The number of investigator-reported hyperglycemic events was 16 (10%) in the liraglutide group vs 27 (18%) in the placebo group and hypoglycemic events were infrequent (2 [1%] vs 4 [3%], respectively). CONCLUSIONS AND RELEVANCE Among patients recently hospitalized with heart failure and reduced LVEF, the use of liraglutide did not lead to greater posthospitalization clinical stability. These findings do not support the use of liraglutide in this clinical situation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01800968 PMID:27483064
Margulies, Kenneth B; Hernandez, Adrian F; Redfield, Margaret M; Givertz, Michael M; Oliveira, Guilherme H; Cole, Robert; Mann, Douglas L; Whellan, David J; Kiernan, Michael S; Felker, G Michael; McNulty, Steven E; Anstrom, Kevin J; Shah, Monica R; Braunwald, Eugene; Cappola, Thomas P
2016-08-02
Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status. To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized. Patients were enrolled between August 2013 and March 2015 at 24 US sites. The GLP-1 agonist liraglutide (n = 154) or placebo (n = 146) via a daily subcutaneous injection; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days. The primary end point was a global rank score in which all patients, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days. Higher values indicate better health (stability). Exploratory secondary outcomes included primary end point components, cardiac structure and function, 6-minute walk distance, quality of life, and combined events. Among the 300 patients who were randomized (median age, 61 years [interquartile range {IQR}, 52-68 years]; 64 [21%] women; 178 [59%] with type 2 diabetes; median LVEF of 25% [IQR, 19%-33%]; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [IQR, 1054-4235 pg/mL]), 271 completed the study. Compared with placebo, liraglutide had no significant effect on the primary end point (mean rank of 146 for the liraglutide group vs 156 for the placebo group, P = .31). There were no significant between-group differences in the number of deaths (19 [12%] in the liraglutide group vs 16 [11%] in the placebo group; hazard ratio, 1.10 [95% CI, 0.57-2.14]; P = .78) or rehospitalizations for heart failure (63 [41%] vs 50 [34%], respectively; hazard ratio, 1.30 [95% CI, 0.89-1.88]; P = .17) or for the exploratory secondary end points. Prespecified subgroup analyses in patients with diabetes did not reveal any significant between-group differences. The number of investigator-reported hyperglycemic events was 16 (10%) in the liraglutide group vs 27 (18%) in the placebo group and hypoglycemic events were infrequent (2 [1%] vs 4 [3%], respectively). Among patients recently hospitalized with heart failure and reduced LVEF, the use of liraglutide did not lead to greater posthospitalization clinical stability. These findings do not support the use of liraglutide in this clinical situation. clinicaltrials.gov Identifier: NCT01800968.
Elvan, Arif; Adiyaman, Ahmet; Beukema, Rypko J; Sie, Hauw T; Allessie, Maurits A
2013-03-01
The electrophysiologic effects of acute atrial dilatation and dedilatation in humans with chronic atrial fibrillation remains to be elucidated. To study the electrophysiological effects of acute atrial dedilatation and subsequent dilatation in patients with long-standing persistent atrial fibrillation (AF) with structural heart disease undergoing elective cardiac surgery. Nine patients were studied. Mean age was 71 ± 10 years, and left ventricular ejection was 46% ± 6%. Patients had at least moderate mitral valve regurgitation and dilated atria. After sternotomy and during extracorporal circulation, mapping was performed on the beating heart with 2 multielectrode arrays (60 electrodes each, interelectrode distance 1.5 mm) positioned on the lateral wall of the right atrium (RA) and left atrium (LA). Atrial pressure and size were altered by modifying extracorporal circulation. AF electrograms were recorded at baseline after dedilation and after dilatation of the atria afterward. At baseline, the median AF cycle length (mAFCL) was 184 ± 27 ms in the RA and 180 ± 17 ms in the LA. After dedilatation, the mAFCL shortened significantly to 168 ± 13 ms in the RA and to 168 ± 20 ms in the LA. Dilatation lengthened mAFCL significantly to 189 ± 17 ms in the RA and to 185 ± 23 ms in the LA. Conduction block (CB) at baseline was 14.3% ± 3.6% in the RA and 17.3% ± 5.5% in the LA. CB decreased significantly with dedilatation to 7.4% ± 2.9% in the RA and to 7.9% ± 6.3% in the LA. CB increased significantly with dilatation afterward to 15.0% ± 8.3% in the RA and to 18.5% ± 16.0% in the LA. Acute dedilatation of the atria in patients with long-standing persistent AF causes a decrease in the mAFCL in both atria. Subsequent dilatation increased the mAFCL. The amount of CB decreased with dedilatation and increased with dilatation afterward in both atria. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Bleeding with the artificial heart: Gastrointestinal hemorrhage in CF-LVAD patients.
Gurvits, Grigoriy E; Fradkov, Elena
2017-06-14
Continuous-flow left ventricular assist devices (CF-LVADs) have significantly improved outcomes for patients with end-stage heart failure when used as a bridge to cardiac transplantation or, more recently, as destination therapy. However, its implantations carries a risk of complications including infection, device malfunction, arrhythmias, right ventricular failure, thromboembolic disease, postoperative and nonsurgical bleeding. A significant number of left ventricular assist devices (LVAD) recipients may experience recurrent gastrointestinal hemorrhage, mainly due to combination of antiplatelet and vitamin K antagonist therapy, activation of fibrinolytic pathway, acquired von Willebrand factor deficiency, and tendency to develop small intestinal angiodysplasias due to increased rotary speed of the pump. Gastrointestinal bleeding in LVAD patients remains a source of increased morbidity including the need for blood transfusions, extended hospital stays, multiple readmissions, and overall mortality. Management of gastrointestinal bleeding in LVAD patients involves multidisciplinary approach in stabilizing the patients, addressing risk factors and performing structured endoluminal evaluation with focus on upper gastrointestinal tract including jejunum to find and eradicate culprit lesion. Medical and procedural intervention is largely successful and universal bleeding cessation occurs in transplanted patients.
Aiello, Vera D; Ferreira, Flávia C N; Scanavacca, Mauricio I; Anderson, Robert H; D'Avila, André
2016-02-01
Patients with congenitally corrected transposition frequently benefit from re-synchronisation therapy or ablation procedures. This is likely to require catheterisation of the coronary sinus. Its anatomy, however, is not always appreciated, despite being well-described. With this caveat in mind, we have evaluated its location and structure in hearts with congenitally corrected transposition in order to reinforce the guidance needed by the cardiac interventionist. We dissected and inspected the coronary sinus, the oblique vein of the left atrium, and the left-sided-circumflex venous channel in eight heart specimens with corrected transposition and eight controls, measuring the orifice and length of the sinus and the atrioventricular valves. In two-thirds of the malformed hearts, the sinus deviated from its anticipated course in the atrioventricular groove, ascending obliquely on the left atrial inferior wall to meet the left oblique vein. The maximal deviation coincided in all hearts with the point where the left oblique vein joined the left-sided-circumflex vein to form the coronary sinus. We describe a circumflex vein, rather than the great cardiac vein, as the latter venous channel is right-sided in the setting of corrected transposition. The length of the sinus correlated positively with the diameter of the tricuspid valve (p=0.02). Compared with controls, the left oblique vein in the malformed hearts joined the circumflex venous channel significantly closer to the mouth of the sinus. The unexpected course of the coronary sinus in corrected transposition and the naming of the cardiac veins have important implications for venous cannulation and interpretation of images.
Morphological description of great cardiac vein in pigs compared to human hearts.
Alejandro Gómez, Fabian; Ballesteros, Luis Ernesto; Stella Cortés, Luz
2015-01-01
In spite of its importance as an experimental model, the information on the great cardiac vein in pigs is sparse. To determine the morphologic characteristics of the great cardiac vein and its tributaries in pigs. 120 hearts extracted from pigs destined to the slaughterhouse with stunning method were studied. This descriptive cross-over study evaluated continuous variables with T test and discrete variables with Pearson χ square test. A level of significance P<0.05 was used. The great cardiac vein and its tributaries were perfused with polyester resin (85% Palatal and 15% Styrene) and then subjected to potassium hydroxide infusion to release the subepicardial fat. Calibers were measured, and trajectories and relations with adjacent arterial structures were evaluated. The origin of the great cardiac vein was observed at the heart apex in 91 (76%) hearts. The arterio-venous trigone was present in 117 (97.5%) specimens, corresponding to the open expression in its lower segment and to the closed expression in the upper segment in the majority of the cases (65%). The caliber of the great cardiac vein at the upper segment of the paraconal interventricular sulcus was 3.73±0.79 mm. An anastomosis between the great cardiac vein and the middle cardiac vein was found in 59 (49%) specimens. The morphological and biometric characteristics of the great cardiac vein and its tributaries had not been reported in prior studies, and due to their similitude with those of the human heart, allows us to propose the pig model for procedural and hemodynamic applications.
Holden, Richard J; Kulanthaivel, Anand; Purkayastha, Saptarshi; Goggins, Kathryn M; Kripalani, Sunil
2017-12-01
Personas are a canonical user-centered design method increasingly used in health informatics research. Personas-empirically-derived user archetypes-can be used by eHealth designers to gain a robust understanding of their target end users such as patients. To develop biopsychosocial personas of older patients with heart failure using quantitative analysis of survey data. Data were collected using standardized surveys and medical record abstraction from 32 older adults with heart failure recently hospitalized for acute heart failure exacerbation. Hierarchical cluster analysis was performed on a final dataset of n=30. Nonparametric analyses were used to identify differences between clusters on 30 clustering variables and seven outcome variables. Six clusters were produced, ranging in size from two to eight patients per cluster. Clusters differed significantly on these biopsychosocial domains and subdomains: demographics (age, sex); medical status (comorbid diabetes); functional status (exhaustion, household work ability, hygiene care ability, physical ability); psychological status (depression, health literacy, numeracy); technology (Internet availability); healthcare system (visit by home healthcare, trust in providers); social context (informal caregiver support, cohabitation, marital status); and economic context (employment status). Tabular and narrative persona descriptions provide an easy reference guide for informatics designers. Personas development using approaches such as clustering of structured survey data is an important tool for health informatics professionals. We describe insights from our study of patients with heart failure, then recommend a generic ten-step personas development process. Methods strengths and limitations of the study and of personas development generally are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.
Genome-wide analysis of alternative splicing during human heart development
NASA Astrophysics Data System (ADS)
Wang, He; Chen, Yanmei; Li, Xinzhong; Chen, Guojun; Zhong, Lintao; Chen, Gangbing; Liao, Yulin; Liao, Wangjun; Bin, Jianping
2016-10-01
Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between foetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.
Perrier-Melo, Raphael José; Figueira, Fernando Augusto Marinho Dos Santos; Guimarães, Guilherme Veiga; Costa, Manoel da Cunha
2018-02-01
Heart transplantation (HTx) is considered an efficient and gold-standard procedure for patients with end-stage heart failure. After surgery, patients have lower aerobic power (VO2max) and compensatory hemodynamic responses. The aim of the present study was to assess through a systematic review with meta-analysis whether high-intensity interval training (HIIT) can provide benefits for those parameters. This is a systematic review with meta-analysis, which searched the databases and data portals PubMed, Web of Science, Scopus, Science Direct and Wiley until December 2016 (pairs). The following terms and descriptors were used: "heart recipient" OR "heart transplant recipient" OR "heart transplant" OR "cardiac transplant" OR "heart graft". Descriptors via DeCS and Mesh were: "heart transplantation'' OR "cardiac transplantation". The words used in combination (AND) were: "exercise training" OR "interval training" OR "high intensity interval training" OR "high intensity training" OR "anaerobic training" OR "intermittent training" OR "sprint training". The initial search identified 1064 studies. Then, only those studies assessing the influence of HIIT on the post-HTx period were added, resulting in three studies analyzed. The significance level adopted was 0.05. Heart transplant recipients showed significant improvement in VO2peak, heart rate and peak blood pressure in 8 to 12 weeks of intervention.
Anguita Sánchez, Manuel; Lambert Rodríguez, José Luis; Bover Freire, Ramón; Comín Colet, Josep; Crespo Leiro, María G; González Vílchez, Francisco; Manito Lorite, Nicolás; Segovia Cubero, Javier; Ruiz Mateas, Francisco; Elola Somoza, Francisco Javier; Íñiguez Romo, Andrés
2016-10-01
The prevalence of heart failure remains high and represents the highest disease burden in Spain. Heart failure units have been developed to systematize the diagnosis, treatment, and clinical follow-up of heart failure patients, provide a structure to coordinate the actions of various entities and personnel involved in patient care, and improve prognosis and quality of life. There is ample evidence on the benefits of heart failure units or programs, which have become widespread in Spain. One of the challenges to the analysis of heart failure units is standardization of their classification, by determining which "programs" can be identified as heart failure "units" and by characterizing their complexity level. The aim of this article was to present the standards developed by the Spanish Society of Cardiology to classify and establish the requirements for heart failure units within the SEC-Excellence project. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
Advances in gene therapy for heart failure.
Fish, Kenneth M; Ishikawa, Kiyotake
2015-04-01
Chronic heart failure is expected to increase its social and economic burden as a consequence of improved survival in patients with acute cardiac events. Cardiac gene therapy holds significant promise in heart failure treatment for patients with currently very limited or no treatment options. The introduction of adeno-associated virus (AAV) gene vector changed the paradigm of cardiac gene therapy, and now it is the primary vector of choice for chronic heart failure gene therapy in clinical and preclinical studies. Recently, there has been significant progress towards clinical translation in this field spearheaded by AAV-1 mediated sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) gene therapy targeting chronic advanced heart failure patients. Meanwhile, several independent laboratories are reporting successful gene therapy approaches in clinically relevant large animal models of heart failure and some of these approaches are expected to enter clinical trials in the near future. This review will focus on gene therapy approaches targeting heart failure that is in clinical trials and those close to its initial clinical trial application.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, R; Liu, T; Qi, S
Purposes: There has been growing interest in treating breast cancer using VMAT technique. Our goal is to compare the dosimetry and treatment delivery parameters for the left-sided breast cancer treatment using various VMAT platforms from commercially available planning systems. Methods: Five consecutive left-sided breast cancer patients initially treated with conventional 3D-conformal radiotherapy (3DCRT) were selected. Four VMAT plans using most popular treatment planning systems, including Eclipse (Version 11, Varian), Pinnacle (Version 9.8, Philips), Monaco (Version 2.03, Elekta) and helical Tomotherapy (V4.0, Accuray). The same structure set and same planning goals were used for all VMAT plans. The dosimetric parameters includingmore » target coverage and minimum/maximum/mean, dose-volume endpoints for the selected normal structures: the heart, ipsilateral-/contralateral lung and breast, were evaluated. Other dosimetric indices including heterogeneity index (HI) were evaluated. The treatment delivery parameters, such as monitor unit (MUs) and delivery time were also compared. Results: VMAT increases dose homogeneity to the treated volume and reduces the irradiated heart and left-lung volumes. Compared to the 3DCRT technique, all VMAT plans offer better heart and left-lung dose sparing; the mean heart doses were 4.5±1.6(Monaco), 1.2±0.4(Pinnacle), 1.3± (Eclipse) and 5.6±4.4(Tomo), the mean left-lung doses were 5.9±1.5(Monaco), 3.7±0.7(Pinnacle), 1.4± (Eclipse) and 5.2±1.6 (Tomo), while for the 3DCRT plan, the mean heart and left-Lung doses were 2.9±2.0, and 6.8±4.4 (Gy) respectively. The averaged contralateral-breast and lung mean doses were higher in VMAT plans than the 3DCRT plans but were not statistically significant. Among all the VMAT plans, the Pinnacle plans often yield the lowest right-lung/breast mean doses, and slightly better heterogeneity indices that are similar to Tomotherapy plans. Treatment delivery time of the VMAT plans (except helical Tomotherapy IMRT) is estimated to be comparable with the conventional 3DCRT. Conclusion: VMAT achieves equal or better PTV coverage and comparable OARs sparing compared to the conventional 3DCRT techniques.« less
Hategan, Lidia; Csányi, Beáta; Ördög, Balázs; Kákonyi, Kornél; Tringer, Annamária; Kiss, Orsolya; Orosz, Andrea; Sághy, László; Nagy, István; Hegedűs, Zoltán; Rudas, László; Széll, Márta; Varró, András; Forster, Tamás; Sepp, Róbert
2017-08-15
The most important molecular determinant of heart rate regulation in sino-atrial pacemaker cells includes hyperpolarization-activated, cyclic nucleotide-gated ion channels, the major isoform of which is encoded by the HCN4 gene. Mutations affecting the HCN4 gene are associated primarily with sick sinus syndrome. A novel c.1737+1 G>T 'splice-site' HCN4 mutation was identified in a large family with familial bradycardia which co-segregated with the disease providing a two-point LOD score of 4.87. Twelve out of the 22 investigated family members [4 males, 8 females average age 36 (SD 6) years] were considered as clinically affected (heart rate<60/min on resting ECG). Minimum [36 (SD 7) vs. 47 (SD 5) bpm, p=0.0087) and average heart rates [62 (SD 8) vs. 73 (SD 8) bpm, p=0.0168) were significantly lower in carriers on 24-hour Holter recordings. Under maximum exercise test carriers achieved significantly lower heart rates than non-carrier family members, and percent heart rate reserve and percent corrected heart rate reserve were significantly lower in carriers. Applying rigorous criteria for chronotropic incompetence a higher number of carriers exhibited chronotropic incompetence. Parameters, characterizing short-term variability of heart rate (i.e. rMSSD and pNN50%) were increased in carrier family members, even after normalization for heart rate, in the 24-hour ECG recordings with the same relative increase in 5-minute recordings. The identified novel 'splice site' HCN4 gene mutation, c.1737+1 G>T, causes familial bradycardia and leads to reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability in the mutation carriers. Copyright © 2017 Elsevier B.V. All rights reserved.
Mashin, V A; Mashina, M N
2004-12-01
In the paper, outcomes of the researches devoted to factor analysis of heart rate variability parameters and definition of the most informative parameters for diagnostics of functional states and an evaluation of level of stability to mental loads, are presented. The factor structure of parameters, which unclude integral level of heart rate variability (1), balance between activity of vagus and brain cortical-limbic systems (2), integrated level of cardiovascular system functioning (3), is substantiated. Factor analysis outcomes have been used for construction of functional state classification, for their differential diagnostics, and for development and check of algorithm for evaluation of the stability level in mental loads.
Speckle variance optical coherence tomography of blood flow in the beating mouse embryonic heart.
Grishina, Olga A; Wang, Shang; Larina, Irina V
2017-05-01
Efficient separation of blood and cardiac wall in the beating embryonic heart is essential and critical for experiment-based computational modelling and analysis of early-stage cardiac biomechanics. Although speckle variance optical coherence tomography (SV-OCT) relying on calculation of intensity variance over consecutively acquired frames is a powerful approach for segmentation of fluid flow from static tissue, application of this method in the beating embryonic heart remains challenging because moving structures generate SV signal indistinguishable from the blood. Here, we demonstrate a modified four-dimensional SV-OCT approach that effectively separates the blood flow from the dynamic heart wall in the beating mouse embryonic heart. The method takes advantage of the periodic motion of the cardiac wall and is based on calculation of the SV signal over the frames corresponding to the same phase of the heartbeat cycle. Through comparison with Doppler OCT imaging, we validate this speckle-based approach and show advantages in its insensitiveness to the flow direction and velocity as well as reduced influence from the heart wall movement. This approach has a potential in variety of applications relying on visualization and segmentation of blood flow in periodically moving structures, such as mechanical simulation studies and finite element modelling. Picture: Four-dimensional speckle variance OCT imaging shows the blood flow inside the beating heart of an E8.5 mouse embryo. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Nachar, Nadim; Lavoie, Marc E; Marchand, André; O'Connor, Kieron P; Guay, Stéphane
2014-09-30
Individuals with posttraumatic stress disorder (PTSD) commonly make efforts to avoid trauma-oriented conversations with their significant others, which may interfere with the natural recovery process. Trauma-oriented conversations can be experienced as physiologically arousing, depending on the intensity of PTSD symptoms and perceptions of social support. In the current investigation, changes in heart rate responses to a trauma-oriented social interaction with a significant other were assessed. Perceived supportive and unsupportive or negative social interactions were examined as moderators of the association between heart rate changes to this context and intensity of PTSD symptoms. A total of 46 individuals with PTSD completed diagnostic interviews and self-report measures of symptoms and perceived supportive and negative social interactions during a trauma-oriented social interaction with a significant other. Heart rate was continuously measured during this interaction. Results showed that engagement in a trauma-oriented social interaction was predictive of elevations in heart rate that positively correlated with intensity of PTSD symptoms. The moderation hypothesis was partially supported. In addition, perceived negative social interactions positively correlated with elevations in heart rate. These findings can inform social intervention efforts for individuals with PTSD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Kang, Seol-Jung; Kim, Eon-Ho; Ko, Kwang-Jun
2016-06-01
[Purpose] The purpose of this study was to investigate the effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness or female patients with metabolic syndrome. [Subjects and Methods] Subjects were randomly assigned to an exercise group (n=12) or a control group (n=11). Subjects in the exercise group performed aerobic exercise at 60-80% of maximum heart rate for 40 min 5 times a week for 12 weeks. The changes in metabolic syndrome risk factors, resting heart rate, physical fitness, and arterial stiffness were measured and analyzed before and after initiation of the exercise program to determine the effect of exercise. Arterial stiffness was assessed based on brachial-ankle pulse wave velocity (ba-PWV). [Results] Compared to the control group; The metabolic syndrome risk factors (weight, % body fat, waist circumference, systolic blood pressure, diastolic blood pressure, and HDL-Cholesterol) were significantly improved in the exercise: resting heart rate was significantly decreased; VO2max, muscle strength and muscle endurance were significantly increased; and ba-PWV was significantly decreased. [Conclusion] Aerobic exercise had beneficial effects on the resting heart rate, physical fitness, and arterial stiffness of patients with metabolic syndrome.
Park, Junbeom; Yang, Pil-sung; Kim, Tae-Hoon; Uhm, Jae-Sun; Kim, Joung-Youn; Joung, Boyoung; Lee, Moon-Hyoung; Hwang, Chun; Pak, Hui-Nam
2015-01-01
Stiff left atrial (LA) syndrome was initially reported in post-cardiac surgery patients and known to be associated with low LA compliance. We investigated the physiological and clinical implications of LA compliance by estimating LA pulse pressure (LApp) among patients with atrial fibrillation (AF) and structurally and functionally normal heart. Among 1038 consecutive patients with LA pressure measurements before AF ablation, we included 334 patients with structurally and functionally normal heart (81.7% male, 54.1±10.6 years, 77.0% paroxysmal AF) after excluding those with hypertension, diabetes, and previous ablation or cardiac surgery. We measured LApp (peak-nadir LA pressure) at the beginning of the ablation procedure and compared the values with clinical parameters and the AF recurrence rate. AF patients with normal heart were younger and more frequently male and had paroxysmal AF, a lower body mass index, and a lower LApp compared to others (all p<0.05). Based on the median value, the low LA compliance group (LApp≥13 mmHg) had a smaller LA volume index and lower LA voltage (all p<0.05) compared to the high LA compliance group. During a mean follow-up of 16.7±11.8 months, low LA compliance was independently associated with two fold-higher risk of clinical AF recurrence (HR:2.202; 95%CI:1.077-4.503; p = 0.031). Low LA compliance, as determined by an elevated LApp, was associated with a smaller LA volume index and lower LA voltage and independently associated with higher clinical recurrence after catheter ablation in AF patients with structurally and functionally normal heart.