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Sample records for adverse ventricular remodeling

  1. The Adverse Impact of Diabetes Mellitus on Left Ventricular Remodeling and Function in Patients with Severe Aortic Stenosis

    PubMed Central

    Lindman, Brian R.; Arnold, Suzanne V.; Madrazo, José A.; Zajarias, Alan; Johnson, Stephanie N.; Pérez, Julio E.; Mann, Douglas L.

    2011-01-01

    Background The diabetic heart exhibits increased left ventricular (LV) mass and reduced ventricular function. However, this relationship has not been studied in patients with aortic stenosis (AS), a disease process that causes LV hypertrophy and dysfunction through a distinct mechanism of pressure overload. The aim of this study was to determine how diabetes mellitus (DM) impacts LV remodeling and function in patients with severe AS. Methods and Results Echocardiograms were performed on 114 patients with severe AS [mean aortic valve area (AVA) 0.6 cm2] and included measures of LV remodeling and function. Multivariable linear regression models investigated the independent effect of DM on these aspects of LV structure and function. Compared to non-diabetics (n=60), diabetics (n=54) had increased LV mass, LV end-systolic dimension, LV end-diastolic dimension, and decreased LV ejection fraction (EF) and longitudinal systolic strain (p<0.01 for all). In multivariable analyses adjusting for age, sex, systolic BP, AVA, BSA, and coronary disease, DM was an independent predictor of increased LV mass (β=26g, p=0.01), LV end-systolic dimension (β=0.5cm, p=0.008), and LV end-diastolic dimension (β=0.3cm, p=0.025). After additionally adjusting for LV mass, DM was associated with reduced longitudinal systolic strain (β=1.9%, p=0.023) and a trend toward reduced EF (β=−5%, p=0.09). Among diabetics, insulin use (as a marker of disease severity) was associated with larger LV end-systolic dimension and worse LV function. LV mass was a strong predictor of reduced EF and systolic strain (p<0.001 for both). Conclusions DM has an additive adverse effect on hypertrophic remodeling—increased LV mass and larger cavity dimensions—and is associated with reduced systolic function in patients with AS beyond known factors of pressure overload. PMID:21357546

  2. Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

    2016-01-01

    Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

  3. Biodegradable elastic patch plasty ameliorates left ventricular adverse remodeling after ischemia–reperfusion injury: A preclinical study of a porous polyurethane material in a porcine model

    PubMed Central

    Hashizume, Ryotaro; Fujimoto, Kazuro L.; Hong, Yi; Guan, Jianjun; Toma, Catalin; Tobita, Kimimasa; Wagner, William R.

    2013-01-01

    Objective Myocardial infarction (MI) can lead to irreversible adverse left ventricular remodeling resulting in subsequent severe dysfunction. The objective of this study was to investigate the potential for biodegradable, elastomeric patch implantation to positively alter the remodeling process after MI in a porcine model. Methods Yorkshire pigs underwent a 60-minute catheter balloon occlusion of the left circumflex artery. Two weeks after MI animals underwent epicardial placement of a biodegradable, porous polyurethane (poly(ester urethane)urea; PEUU) patch (MI+PEUU, n = 7) or sham surgery (MI+sham, n = 8). Echocardiography before surgery and at 4 and 8 weeks after surgery measured the end-diastolic area (EDA) and fractional area change (% FAC). All animals were humanely killed 8 weeks after surgery and hearts were histologically assessed. Results At 8 weeks, echocardiography revealed greater EDA values in the MI+sham group (23.6 ± 6.6 cm2 , mean ± standard deviaation) than in the MI+PEUU group (15.9 ± 2.5 cm2) (P < .05) and a lower %FAC in the MI+sham group (24.8 ± 7.6) than in the MI+PEUU group (35.9 ± 7.8) (P < .05). The infarcted ventricular wall was thicker in the MI+PEUU group (1.56 ± 0.5 cm) than in the MI+sham group (0.91 ± 0.24 cm) (P < .01). Conclusions Biodegradable elastomeric PEUU patch implantation onto the porcine heart 2 weeks post-MI attenuated left ventricular adverse remodeling and functional deterioration and was accompanied by increased neovascularization. These findings, although limited to a 2-month follow-up, may suggest an attractive clinical option to moderate post-MI cardiac failure. PMID:23219497

  4. Association of the Frontal QRS-T Angle with Adverse Cardiac Remodeling, Impaired Left and Right Ventricular Function, and Worse Outcomes in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Selvaraj, Senthil; Ilkhanoff, Leonard; Burke, Michael A.; Freed, Benjamin H.; Lang, Roberto M.; Martinez, Eva E.; Shah, Sanjiv J.

    2013-01-01

    Background No prior studies have investigated the association of QRS-T angle with cardiac structure/function and outcomes in heart failure with preserved ejection fraction (HFpEF). We hypothesized that increased frontal QRS-T angle is associated with worse cardiac function/remodeling and adverse outcomes in HFpEF. Methods We prospectively studied 376 patients with HFpEF (i.e. symptomatic HF with left ventricular [LV] ejection fraction >50%.) The frontal QRS-T angle was calculated from the 12-lead electrocardiogram. Patients were divided into tertiles by frontal QRS-T angle (0–26°, 27–75°, and 76–179°), and clinical, laboratory, and echocardiographic data were compared among groups. Cox proportional hazards analyses were performed to determine the association between QRS-T angle and outcomes. Results The mean age of the cohort was 64±13 years, 65% were women, and the mean QRS-T angle was 61±51°. Patients with increased QRS-T angle were older, had a lower body-mass index, more frequently had coronary artery disease, diabetes, chronic kidney disease, and atrial fibrillation, and had higher B-type natriuretic peptide (BNP) levels (P<0.05 for all comparisons). After multivariable adjustment, patients with increased QRS-T angle had higher BNP levels in addition to higher LV mass index, worse diastolic function parameters, more right ventricular (RV) remodeling, and worse RV systolic function (P<0.05 for all associations). QRS-T angle was independently associated with the composite outcome of cardiovascular hospitalization or death on multivariable analysis, even after adjusting for BNP (HR for the highest QRS-T tertile = 2.0, 95% CI 1.2–3.4; P=0.008). Conclusions In HFpEF, increased QRS-T angle is independently associated with worse left and right ventricular function/remodeling and adverse outcomes. PMID:24075945

  5. Rapid Surface Cooling by ThermoSuit System Dramatically Reduces Scar Size, Prevents Post-Infarction Adverse Left Ventricular Remodeling, and Improves Cardiac Function in Rats

    PubMed Central

    Dai, Wangde; Herring, Michael J; Hale, Sharon L; Kloner, Robert A

    2015-01-01

    Background The long-term effects of transient hypothermia by the non-invasive ThermoSuit apparatus on myocardial infarct (MI) scar size, left ventricular (LV) remodeling, and LV function were assessed in rat MI model. Methods and Results Rats were randomized to normothermic or hypothermic groups (n=14 in each group) and subjected to 30 minutes coronary artery occlusion and 6 weeks of reperfusion. For hypothermia therapy, rats were placed into the ThermoSuit apparatus at 2 minutes after the onset of coronary artery occlusion, were taken out of the apparatus when the core body temperature reached 32°C (in ≈8 minutes), and were then allowed to rewarm. After 6 weeks of recovery, rats treated with hypothermia demonstrated markedly reduced scar size (expressed as % of left ventricular area: hypothermia, 6.5±1.1%; normothermia, 19.4±1.7%; P=1.3×10−6); and thicker anterior LV wall (hypothermia, 1.57±0.09 mm; normothermia, 1.07±0.05 mm; P=3.4×10−5); decreased postmortem left ventricular volume (hypothermia, 0.45±0.04 mL; normothermia, 0.6±0.03 mL; P=0.028); and better LV fractional shortening by echocardiography (hypothermia, 37.2±2.8%; normothermia, 18.9±2.3%; P=0.0002) and LV ejection fraction by LV contrast ventriculography (hypothermia, 66.8±2.3%; normothermia, 56.0±2.0%; P=0.0014). Conclusions Rapid, transient non-invasive surface cooling with the ThermoSuit apparatus in the acute phase of MI decreased scar size by 66.5%, attenuated adverse post-infarct left ventricular dilation and remodeling, and improved cardiac function in the chronic phase of experimental MI. PMID:26116692

  6. Postinfarct Left Ventricular Remodelling: A Prevailing Cause of Heart Failure

    PubMed Central

    Galli, Alessio; Lombardi, Federico

    2016-01-01

    Heart failure is a chronic disease with high morbidity and mortality, which represents a growing challenge in medicine. A major risk factor for heart failure with reduced ejection fraction is a history of myocardial infarction. The expansion of a large infarct scar and subsequent regional ventricular dilatation can cause postinfarct remodelling, leading to significant enlargement of the left ventricular chamber. It has a negative prognostic value, because it precedes the clinical manifestations of heart failure. The characteristics of the infarcted myocardium predicting postinfarct remodelling can be studied with cardiac magnetic resonance and experimental imaging modalities such as diffusion tensor imaging can identify the changes in the architecture of myocardial fibers. This review discusses all the aspects related to postinfarct left ventricular remodelling: definition, pathogenesis, diagnosis, consequences, and available therapies, together with experimental interventions that show promising results against postinfarct remodelling and heart failure. PMID:26989555

  7. Passive ventricular remodeling in cardiac disease: focus on heterogeneity

    PubMed Central

    Kessler, Elise L.; Boulaksil, Mohamed; van Rijen, Harold V. M.; Vos, Marc A.; van Veen, Toon A. B.

    2014-01-01

    Passive ventricular remodeling is defined by the process of molecular ventricular adaptation to different forms of cardiac pathophysiology. It includes changes in tissue architecture, such as hypertrophy, fiber disarray, alterations in cell size and fibrosis. Besides that, it also includes molecular remodeling of gap junctions, especially those composed by Connexin43 proteins (Cx43) in the ventricles that affect cell-to-cell propagation of the electrical impulse, and changes in the sodium channels that modify excitability. All those alterations appear mainly in a heterogeneous manner, creating irregular and inhomogeneous electrical and mechanical coupling throughout the heart. This can predispose to reentry arrhythmias and adds to a further deterioration into heart failure. In this review, passive ventricular remodeling is described in Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM), and Arrhythmogenic Cardiomyopathy (ACM), with a main focus on the heterogeneity of those alterations mentioned above. PMID:25566084

  8. Relationship between Left Ventricular Structural and Metabolic Remodelling in Type 2 Diabetes Mellitus

    PubMed Central

    Levelt, Eylem; Mahmod, Masliza; Piechnik, Stefan K.; Ariga, Rina; Francis, Jane M.; Rodgers, Christopher T.; Clarke, William T.; Sabharwal, Nikant; Schneider, Jurgen E.; Karamitsos, Theodoros D.; Clarke, Kieran; Rider, Oliver J.; Neubauer, Stefan

    2016-01-01

    Concentric left ventricular (LV) remodelling is associated with adverse cardiovascular events and is frequently observed in patients with type 2 diabetes mellitus (T2DM). Despite this, the cause of concentric remodelling in diabetes, per se, is unclear, but may be related to cardiac steatosis and impaired myocardial energetics. Thus, we investigated the relationship amongst myocardial metabolic changes and LV remodelling in T2DM. Forty-six non-hypertensive T2DM patients and twenty matched controls underwent cardiovascular magnetic resonance to assess LV remodelling (LV mass to LV end diastolic volume ratio-LVMVR), function, pre- and post-contrast tissue characterisation using T1 mapping, 1H-, 31P-magnetic resonance spectroscopy for myocardial triglyceride content (MTG) and phosphocreatine to ATP ratio (PCr/ATP) respectively. When compared to body mass index and blood pressure matched controls, diabetes was associated with: concentric LV remodelling, higher MTG, impaired myocardial energetics and impaired systolic strain indicating a subtle contractile dysfunction. Importantly, cardiac steatosis independently predicted concentric remodelling and systolic strain. Extracellular volume fraction was unchanged, indicating absence of fibrosis. In conclusion, cardiac steatosis may contribute to LV concentric remodelling and contractile dysfunction in diabetes. As cardiac steatosis is modifiable, strategies aimed at reducing myocardial triglyceride may be beneficial in reversing concentric remodelling and improving contractile function in the diabetic heart. PMID:26438611

  9. Using Extracellular Matrix Proteomics: To Understand Left Ventricular Remodeling

    PubMed Central

    Lindsey, Merry L.; Weintraub, Susan T.; Lange, Richard A.

    2011-01-01

    Survival following myocardial infarction (MI) has improved substantially over the last 40 years; however, the incidence of subsequent congestive heart failure has dramatically increased as a consequence. Discovering plasma markers that signify adverse cardiac remodeling may allow high-risk patients to be recognized earlier and may provide an improved way to assess treatment efficacy. Alterations in extracellular matrix (ECM) regulate cardiac remodeling following MI and potentially provide a large array of candidate indicators. The field of cardiac proteomics has progressed rapidly over the past 20 years, since publication of the first two-dimensional electrophoretic gels of left ventricle proteins. Proteomic approaches are now routinely utilized to better understand how the left ventricle responds to injury. In this review, we will discuss how methods have developed to allow comprehensive evaluation of the ECM proteome. We will explain how ECM proteomic data can be used to predict adverse remodeling for an individual patient and highlight future directions. Although this review will focus on the use of ECM proteomics to better understand post-MI remodeling responses, these approaches have applicability to a wide-range of cardiac pathologies, including pressure overload hypertrophy, viral myocarditis, and non-ischemic heart failure. PMID:22337931

  10. Post-Infarct biomaterials, left ventricular remodeling, and heart failure: Is good good enough?

    PubMed Central

    Zouein, Fouad A.; Zgheib, Carlos; Liechty, Kenneth W.; Booz, George W.

    2012-01-01

    Infarct expansion and extension of the border zone play a key role in the progression of heart failure after myocardial infarction. Increased wall stress, along with complex cellular and extracellular changes in the surviving myocardium, underlie these events and contributes to the adverse cardiac remodeling that drives ventricular dilation and progression of heart failure. Recently, there has been much interest in the development of biopolymers that can be injected into the infarcted myocardium in order to increase its stiffness and thus reduce mechanical stress on the surrounding myocardium. Here we discuss the findings of recent animal studies that have noted improvements in contractile function or cardiac remodeling using either natural or synthetic biomaterials, as well as several that did not. Besides offering physical support to the injured myocardium, injectable biomaterials could also serve the purpose of fostering cardiac repair by functioning as a protective scaffold for stem cell or drug delivery. PMID:22612796

  11. Orphan nuclear receptor Nur77 affects cardiomyocyte calcium homeostasis and adverse cardiac remodelling

    PubMed Central

    Medzikovic, Lejla; Schumacher, Cees A.; Verkerk, Arie O.; van Deel, Elza D.; Wolswinkel, Rianne; van der Made, Ingeborg; Bleeker, Natascha; Cakici, Daniella; van den Hoogenhof, Maarten M. G.; Meggouh, Farid; Creemers, Esther E.; Ann Remme, Carol; Baartscheer, Antonius; de Winter, Robbert J.; de Vries, Carlie J. M.; Arkenbout, E. Karin; de Waard, Vivian

    2015-01-01

    Distinct stressors may induce heart failure. As compensation, β-adrenergic stimulation enhances myocardial contractility by elevating cardiomyocyte intracellular Ca2+ ([Ca2+]i). However, chronic β-adrenergic stimulation promotes adverse cardiac remodelling. Cardiac expression of nuclear receptor Nur77 is enhanced by β-adrenergic stimulation, but its role in cardiac remodelling is still unclear. We show high and rapid Nur77 upregulation in cardiomyocytes stimulated with β-adrenergic agonist isoproterenol. Nur77 knockdown in culture resulted in hypertrophic cardiomyocytes. Ventricular cardiomyocytes from Nur77-deficient (Nur77-KO) mice exhibited elevated diastolic and systolic [Ca2+]i and prolonged action potentials compared to wild type (WT). In vivo, these differences resulted in larger cardiomyocytes, increased expression of hypertrophic genes, and more cardiac fibrosis in Nur77-KO mice upon chronic isoproterenol stimulation. In line with the observed elevated [Ca2+]i, Ca2+-activated phosphatase calcineurin was more active in Nur77-KO mice compared to WT. In contrast, after cardiac pressure overload by aortic constriction, Nur77-KO mice exhibited attenuated remodelling compared to WT. Concluding, Nur77-deficiency results in significantly altered cardiac Ca2+ homeostasis and distinct remodelling outcome depending on the type of insult. Detailed knowledge on the role of Nur77 in maintaining cardiomyocyte Ca2+ homeostasis and the dual role Nur77 plays in cardiac remodelling will aid in developing personalized therapies against heart failure. PMID:26486271

  12. Prolonged Ventricular Asystole: A Rare Adverse Effect of Hydrocodone Use

    PubMed Central

    Sudhakaran, Sivakumar; Surani, Saherish S.; Surani, Salim R.

    2014-01-01

    Patient: Female, 56 Final Diagnosis: Ventricular asystole Symptoms: Dizziness, headache, near-syncope, weakness Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Prolonged ventricular asystole is a rare vagal reaction caused by hydrocodone use. Sinus bradycardia is a characteristic presentation of the vasovagal response; examples of other presentations include arrest or atrioventricular block. Physicians need to be aware of ventricular asystole due to vagally-mediated atrioventricular block caused by hydrocodone or other opiates. Case Report: We present a case of prolonged ventricular asystole in a young patient due to a vasovagal reaction caused by the hydrocodone found in the hydrocodone/acetaminophen combination. Conclusions: Ventricular asystole can be a rare complication of hydrocodone found in hydrocodone/acetaminophen. Physicians need to be aware of this adverse effect, rather then resorting to expensive diagnostic interventions. PMID:25330933

  13. [The process of ventricular remodeling after acute myocardial infarct associated with left ventricular aneurysm and ventricular septum rupture treated with radical surgery].

    PubMed

    Hůla, J

    1997-01-01

    Even after a successful operation of mechanical complications on account of acute myocardial infarction gradually developing adverse remodelling of the left ventricle has to be envisaged. In a six-year clinical study by means of echocardiography the authors followed up systematically some cardiac dimensions and volumes and functional systolic and diastolic left ventricular parameters. The changes pertained in particular to the endsystolic and enddiastolic volume, the ejection fraction, the peak maximum rate, early and late diastolic filling and their ratio as well as to indirect values of the mean pressure in the pulmonary artery. These changes, which at first indicated impaired relaxation, are caused subsequently by increasing stiffness of the left ventricle. With regard to the large number of complicated pathophysiological phenomena pertaining to active relaxation and passive elastic properties of the left ventricle during ventricular diastole, different Doppler parameters must be evaluated very carefully, individually and with regard to the clinical condition. Attention is drawn to the importance of complicating mitral regurgitations and an increased pressure in the left atrium and lesser circulation after aneurysmectomy of the left ventricle. Mitral regurgitation has an impact on the process of left ventricular filling investigated by means of diastolic Doppler functions. Despite limitations of echocardiographic methods within the framework of assessment of diastolic left ventricular functions after myocardial infarction echocardiography remains the main means for evaluating left ventricular function by a non-invasive route and its position in this respect is irreplaceable. Further experimental work is needed for better understanding, use and more intelligent interpretation of non-invasive parameters of left ventricular function also in these complicated conditions after surgery of mechanical complications resulting from myocardial infarction. PMID:9221569

  14. Echocardiographic Predictors for Left Ventricular Remodeling after Acute ST Elevation Myocardial Infarction with Low Risk Group: Speckle Tracking Analysis

    PubMed Central

    Na, Hyun-Min; Lee, Joo Myung; Cha, Myung-Jin; Yoon, Yeonyee E.; Lee, Seung-Pyo; Kim, Hyung-Kwan; Kim, Yong-Jin; Sohn, Dae-Won

    2016-01-01

    Background We sought to assess echocardiographic predictors of left ventricular (LV) adverse remodeling after successfully reperfused acute ST elevation myocardial infarction (STEMI). LV remodeling is commonly found in STEMI patients and it may suggest adverse outcome in acute myocardial infarction. We sought to identify whether 2D strain and torsion be independent parameters for prediction of LV adverse remodeling. Methods We investigated 208 patients with low-risk STEMI patients who had follow up echocardiography at 6 or more months. After clinical assessments, all patients received revascularization according to current guideline. LV remodeling was defined as > 20% increase in end-diastolic volume (EDV) at follow up. Results During the follow-up (11.9 ± 5.3 months), 53 patients (25.5%) showed LV remodeling. In univariate analysis, EDV, end-systolic volume, deceleration time (DT), CK-MB, and global longitudinal strain (GLS) were associated with LV remodeling. In multivariate analysis, EDV [hazard ratio (HR): 0.922, 95% confidence interval (CI): 0.897–0.948, p< 0.001], GLS (HR: 0.842, 95% CI: 0.728–0.974, p = 0.020), DT (HR: 0.989, 95% CI: 0.980–0.998, p = 0.023) and CK-MB (HR: 1.003, 95% CI: 1.000–1.005, p = 0.033) independently predicted LV remodeling. However, global circumferential strain, net twist, and twist or untwist rate were not associated with remodeling. Conclusion Of various parameters of speckle strain, only GLS predicted adverse remodeling in STEMI patients. PMID:27358705

  15. The relationship between ventricular electrical delay and left ventricular remodelling with cardiac resynchronization therapy

    PubMed Central

    Gold, Michael R.; Birgersdotter-Green, Ulrika; Singh, Jagmeet P.; Ellenbogen, Kenneth A.; Yu, Yinghong; Meyer, Timothy E.; Seth, Milan; Tchou, Patrick J.

    2011-01-01

    Aims The aim of the present study was to evaluate the relationship between left ventricular (LV) electrical delay, as measured by the QLV interval, and outcomes in a prospectively designed substudy of the SMART-AV Trial. Methods and results This was a multicentre study of patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT) defibrillator implantation. In 426 subjects, QLV was measured as the interval from the onset of the QRS from the surface ECG to the first large peak of the LV electrogram. Left ventricular volumes were measured by echocardiography at baseline and after 6 months of CRT by a blinded core laboratory. Quality of life (QOL) was assessed by a standardized questionnaire. When separated by quartiles based on QLV duration, reverse remodelling response rates (>15% reduction in LV end systolic volume) increased progressively from 38.7 to 68.4% and QOL response rate (>10 points reduction) increased from 50 to 72%. Patients in the highest quartile of QLV had a 3.21-fold increase (1.58–6.50, P = 0.001) in their odds of a reverse remodelling response after correcting for QRS duration, bundle branch block type, and clinical characteristics by multivariate logistic regression analysis. Conclusion Electrical dyssynchrony, as measured by QLV, was strongly and independently associated with reverse remodelling and QOL with CRT. Acute measurements of QLV may be useful to guide LV lead placement. PMID:21875862

  16. Ventricular Remodeling in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Shah, Amil M.

    2014-01-01

    Heart failure with preserved ejection fraction (HFpEF) is common, increasing in prevalence, and causes substantial morbidity and mortality. HFpEF has commonly been viewed as an expression of advanced hypertensive heart disease, with a cardiac phenotype characterized by an increase in wall thickness-to-chamber radius ratio (concentric hypertrophy). However, marked clinical heterogeneity within this syndrome is now well appreciated, and is mirrored in the variability in left ventricular structure. A review of larger imaging studies from epidemiology and clinical trial cohorts demonstrate that while concentric LV remodeling is common, it is by no means universal and many patients demonstrate normal LV geometry or even an eccentric pattern. More detailed assessment of cardiac structure and function in broader HFpEF populations will be necessary to better define the prevalence, determinants, and prognostic relevance of these measures, which may in turn serve as a foundation to identify pathophysiologically relevant sub-phenotypes within this diverse syndrome. PMID:24097113

  17. Left ventricular structure and remodeling in patients with COPD

    PubMed Central

    Pelà, Giovanna; Li Calzi, Mauro; Pinelli, Silvana; Andreoli, Roberta; Sverzellati, Nicola; Bertorelli, Giuseppina; Goldoni, Matteo; Chetta, Alfredo

    2016-01-01

    Background Data on cardiac alterations such as left ventricular (LV) hypertrophy, diastolic dysfunction, and lower stroke volume in patients with COPD are discordant. In this study, we investigated whether early structural and functional cardiac changes occur in patients with COPD devoid of manifest cardiovascular disease, and we assessed their associations with clinical and functional features. Methods Forty-nine patients with COPD belonging to all Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes were enrolled and compared with 36 controls. All subjects underwent clinical history assessment, lung function testing, blood pressure measurement, electrocardiography, and conventional and Doppler tissue echocardiography. Patients were also subjected to computed tomography to quantify emphysema score. Results Patients with COPD had lower LV cavity associated with a marked increase in relative wall thickness (RWT), suggesting concentric remodeling without significant changes in LV mass. RWT was significantly associated with ratio of the forced expiratory volume in 1 second to the forced vital capacity and emphysema score and was the only cardiac parameter that – after multivariate analysis – significantly correlated with COPD conditions in all individuals. Receiver operating characteristic curve analysis showed that RWT (with a cutoff point of 0.42) predicted the severity of COPD with 83% specificity and 56% sensitivity (area under the curve =0.69, 95% confidence interval =0.59–0.81). Patients with COPD showed right ventricular to be functional but no structural changes. Conclusion Patients with COPD without evident cardiovascular disease exhibit significant changes in LV geometry, resulting in concentric remodeling. In all individuals, RWT was significantly and independently related to COPD. However, its prognostic role should be determined in future studies. PMID:27257378

  18. Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload

    PubMed Central

    Nielsen, Eva Amalie; Sun, Mei; Honjo, Osami; Hjortdal, Vibeke E.; Redington, Andrew N.; Friedberg, Mark K.

    2016-01-01

    Background Pulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown. Methods Elevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls). Results: Right and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan. Conclusion Isolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload. PMID:26765263

  19. Atrial Remodeling and Atrial Tachyarrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy.

    PubMed

    Wu, Lingmin; Guo, Jinrui; Zheng, Lihui; Chen, Gang; Ding, Ligang; Qiao, Yu; Sun, Wei; Yao, Yan; Zhang, Shu

    2016-09-01

    Less is known about atrial remodeling and atrial tachyarrhythmias (ATa) in arrhythmogenic right ventricular cardiomyopathy (ARVC); this cross-sectional study aimed to determine the prevalence, characterization, and predictors of atrial remodeling and ATa in a large series of patients with ARVC. From February 2004 to September 2014, 294 consecutive patients who met the task force criteria for ARVC were enrolled. The prevalence, characterization, and predictors of atrial dilation and ATa were investigated. Right atrium (RA) dilation was identified in 160 patients (54.4%) and left atrium dilation in 66 patients (22.4%). Both RA and left atrium dilation were found in 44 patients (15.0%). Twenty-five patients (8.5%) had atrial fibrillation (AF), whereas 19 patients (6.5%) had atrial flutter (AFL). Of which, 7 patients (2.4%) had both AF and AFL. Multivariate analysis showed that AFL (odds ratio [OR] 10.309; 95% confidence interval [CI] 2.770 to 38.462; p <0.001), hypertension (OR 9.174; 95% CI 2.364 to 35.714; p = 0.001), and RA dilation (OR 6.993; 95% CI 1.623 to 30.303; p = 0.009) were associated with increased risk for AF. AF (OR 10.526; 95% CI 2.786 to 40.000; p = 0.001) increased the risk of AFL. In conclusion, atrial remodeling and ATa were common in patients with ARVC. PMID:27378141

  20. TNF-α inhibition attenuates adverse myocardial remodeling in a rat model of volume overload

    PubMed Central

    Jobe, Lynetta J.; Meléndez, Giselle C.; Levick, Scott P.; Du, Yan; Brower, Gregory L.

    2009-01-01

    Tumor necrosis factor (TNF)-α is a proinflammatory cytokine that has been implicated in the pathogenesis of heart failure. In contrast, we have recently shown that myocardial levels of TNF-α are acutely elevated in the aortocaval (AV) fistula model of heart failure. Based on these observations, we hypothesized that progression of adverse myocardial remodeling secondary to volume overload would be prevented by inhibition of TNF-α with etanercept. Furthermore, a principal objective of this study was to elucidate the effect of TNF-α inhibition during different phases of the myocardial remodeling process. Eight-week-old male Sprague-Dawley rats were randomly divided into the following three groups: sham-operated controls, untreated AV fistulas, and etanercept-treated AV fistulas. Each group was further subdivided to study three different time points consisting of 3 days, 3 wk, and 8 wk postfistula. Etanercept was administered subcutaneously at 1 mg/kg body wt. Etanercept prevented collagen degradation at 3 days and significantly attenuated the decrease in collagen at 8 wk postfistula. Although TNF-α antagonism did not prevent the initial ventricular dilatation at 3 wk postfistula, etanercept was effective at significantly attenuating the subsequent ventricular hypertrophy, dilatation, and increased compliance at 8 wk postfistula. These positive adaptations achieved with etanercept administration translated into significant functional improvements. At a cellular level, etanercept also markedly attenuated increases in cardiomyocyte length, width, and area at 8 wk postfistula. These observations demonstrate that TNF-α has a pivotal role in adverse myocardial remodeling and that treatment with etanercept can attenuate the progression to heart failure. PMID:19666842

  1. Rutaecarpine attenuates hypoxia-induced right ventricular remodeling in rats.

    PubMed

    Li, Wen-Qun; Li, Xiao-Hui; Du, Jie; Zhang, Wang; Li, Dai; Xiong, Xiao-Ming; Li, Yuan-Jian

    2016-07-01

    Rutaecarpine has been shown to exhibit wide pharmacological effects in the cardiovascular system via stimulation of calcitonin gene-related peptide (CGRP) release. In the present study, the effect of rutaecarpine on hypoxia-induced right ventricular (RV) remodeling and the underlying mechanisms were evaluated. RV remodeling was induced by hypoxia (10 % O2, 3 weeks) in rats. Rats were treated with rutaecarpine (20 or 40 mg/kg) by intragastric administration. Proliferation of cardiac fibroblasts was induced by TGF-β1 (5 ng/mL) and determined by MTS and EdU incorporation method. Cardiac fibroblasts were treated with exogenous CGRP (10 or 100 nM). The concentrations of CGRP and TGF-β1 in plasma were measured by ELISA. The expression of eIF3a, p27, α-SMA, collagen-I/III, ANP, and BNP were measured by real-time PCR or western blot. Hypoxia induced an increase of right ventricle systolic pressure (RVSP), ration of RV/LV+S, and RV/tibial length in rats, while cardiac hypertrophy, apoptosis, and fibrosis were detected. The expression of ANP, BNP, α-SMA, collagen-I, collagen-III, eIF3a, and TGF-β1 was up-regulated, and the expression of p27 was down-regulated in the right ventricle of hypoxia-treated rats. The plasma concentration of CGRP was decreased and TGF-β1 was increased in hypoxia-treated rats. All of these effects induced by hypoxia were attenuated by rutaecarpine in a dose-dependent manner. In cultured cardiac fibroblasts, TGF-β1 significantly promoted the proliferation and up-regulated the expression of α-SMA and collagen-I/III, while the expression of eIF3a was up-regulated and the expression of p27 was down-regulated. The effects of TGF-β1 were attenuated by CGRP. CGRP8-37, a selective CGRP receptor antagonist, abolished the effects of CGRP. Rutaecarpine attenuates hypoxia-induced RV remodeling via stimulation of CGRP release, and the effects of rutaecarpine involve the eIF3a/p27 pathway. PMID:27052575

  2. Acute versus chronic exercise-induced left-ventricular remodeling.

    PubMed

    Weiner, Rory B; Baggish, Aaron L

    2014-11-01

    Exercise-induced cardiac remodeling (EICR) is the process by which the heart adapts to the physiologic stress of exercise. Non-invasive cardiovascular imaging has led to advances in the understanding of EICR, with sport-specific changes in left-ventricular (LV) structure and function being described; however, the majority of data stem from cross-sectional and short-duration longitudinal studies. Due to the paucity of long-term longitudinal EICR studies, the time course of this process and any distinct differentiation between acute and chronic adaptations remain largely unexplored. In order to clarify the natural history of EICR, longer duration longitudinal study is required. Such work will determine whether exercise-induced changes in myocardial structure and function occur in discrete stages. Examination of prolonged exposures to exercise training will also be necessary to determine normative values across the age and training spectrums of athletic patients. This information will help to distinguish the boundary between physiology and pathology in athletic patients. PMID:25300444

  3. Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.

    PubMed

    Thoonen, Robrecht; Ernande, Laura; Cheng, Juan; Nagasaka, Yasuko; Yao, Vincent; Miranda-Bezerra, Alexandre; Chen, Chan; Chao, Wei; Panagia, Marcello; Sosnovik, David E; Puppala, Dheeraj; Armoundas, Antonis A; Hindle, Allyson; Bloch, Kenneth D; Buys, Emmanuel S; Scherrer-Crosbie, Marielle

    2015-07-01

    Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy. PMID:25968336

  4. Adverse ventricular-ventricular interactions in right ventricular pressure load: Insights from pediatric pulmonary hypertension versus pulmonary stenosis.

    PubMed

    Driessen, Mieke M P; Hui, Wei; Bijnens, Bart H; Dragulescu, Andreea; Mertens, Luc; Meijboom, Folkert J; Friedberg, Mark K

    2016-06-01

    Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular

  5. Optimized Local Infarct Restraint Improves Left Ventricular Function and Limits Remodeling

    PubMed Central

    Koomalsingh, Kevin J.; Witschey, Walter R.T.; McGarvey, Jeremy R.; Shuto, Takashi; Kondo, Norihiro; Xu, Chun; Jackson, Benjamin M.; Gorman, Joseph H.; Gorman, Robert C.; Pilla, James J.

    2013-01-01

    Background Preventing expansion and dyskinetic movement of a myocardial infarction (MI) can limit left ventricular (LV) remodeling. Using a device designed to produce variable alteration of infarct stiffness and geometry, we sought to understand how these parameters affect LV function and remodeling early after MI. Methods Ten pigs had posterolateral infarctions. An unexpanded device was placed in 5 animals at the time of infarction, and 5 animals served as untreated controls. One week after MI animals underwent MRI to assess LV size and regional function. In the treatment group, after initial imaging, the device was expanded with 2ml, 4ml, 6ml, 8ml and 10ml of saline. The optimal degree of inflation was defined as that which maximized stroke volume (SV). The device was left optimally inflated in the treatment animals for three additional weeks. Results One week after MI, device inflation to ≥6ml significantly (p<0.05) decreased endsystolic volume (ESV) (0ml:59.9ml±3.8, 6ml:54.0ml≥±3.1, 8ml:50.5ml±4.8, 10ml:46.1ml±2.2) and increased ejection fraction (EF) (0ml:34.6%±1.6, 6ml:39.7%±0.9, 8ml:43.1%±2.7, 10ml:44.1%±0.9). SV significantly (p<0.05) improved for the 6ml and 8ml volumes (0ml: 31.2ml±2.6, 6ml: 35.7ml±2.0, 8ml: 37.5ml±1.9) but trended downward for 10ml (36.6ml±2.8). At four-weeks after MI, end-diastolic volume and ESV were unchanged from one-week values in the treatment group while the control group continued to dilate. SV (38.2±4.4ml vs. 34.0.1±4.8ml, p=0.08) and EF (36.0±2.6% vs. 27.6±1.4%, p=0.04) were also better in the treatment animals. Conclusions Optimized isolated infarct restraint can limit adverse LV remodeling after MI. The tested device affords the potential for a patient-specific therapy to preserve cardiac function after MI. PMID:23146279

  6. Assessment of Left Ventricular Structural Remodelling in Patients with Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance.

    PubMed

    Shang, Yongning; Zhang, Xiaochun; Chen, Liu; Leng, Weiling; Lei, Xiaotian; Yang, Qi; Liang, Ziwen; Wang, Jian

    2016-01-01

    Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM. Methods. Twenty-five patients (53.8 ± 8.8 years, 52.0% males) with DCM and thirty-one normal healthy controls (51.9 ± 13.6 years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E', A', and E'/A') were also measured. Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) (P < 0.05) and no significant difference was in mass at end diastole (P > 0.05). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E' (all P < 0.05). Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM. PMID:27419144

  7. Assessment of Left Ventricular Structural Remodelling in Patients with Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance

    PubMed Central

    Zhang, Xiaochun; Leng, Weiling

    2016-01-01

    Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM. Methods. Twenty-five patients (53.8 ± 8.8 years, 52.0% males) with DCM and thirty-one normal healthy controls (51.9 ± 13.6 years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E′, A′, and E′/A′) were also measured. Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) (P < 0.05) and no significant difference was in mass at end diastole (P > 0.05). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E′ (all P < 0.05). Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM. PMID:27419144

  8. Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling.

    PubMed

    Oka, Toru; Xu, Jian; Kaiser, Robert A; Melendez, Jaime; Hambleton, Michael; Sargent, Michelle A; Lorts, Angela; Brunskill, Eric W; Dorn, Gerald W; Conway, Simon J; Aronow, Bruce J; Robbins, Jeffrey; Molkentin, Jeffery D

    2007-08-01

    The cardiac extracellular matrix is a dynamic structural support network that is both influenced by, and a regulator of, pathological remodeling and hypertrophic growth. In response to pathologic insults, the adult heart reexpresses the secreted extracellular matrix protein periostin (Pn). Here we show that Pn is critically involved in regulating the cardiac hypertrophic response, interstitial fibrosis, and ventricular remodeling following long-term pressure overload stimulation and myocardial infarction. Mice lacking the gene encoding Pn (Postn) were more prone to ventricular rupture in the first 10 days after a myocardial infarction, but surviving mice showed less fibrosis and better ventricular performance. Pn(-/-) mice also showed less fibrosis and hypertrophy following long-term pressure overload, suggesting an intimate relationship between Pn and the regulation of cardiac remodeling. In contrast, inducible overexpression of Pn in the heart protected mice from rupture following myocardial infarction and induced spontaneous hypertrophy with aging. With respect to a mechanism underlying these alterations, Pn(-/-) hearts showed an altered molecular program in fibroblast function. Indeed, fibroblasts isolated from Pn(-/-) hearts were less effective in adherence to cardiac myocytes and were characterized by a dramatic alteration in global gene expression (7% of all genes). These are the first genetic data detailing the function of Pn in the adult heart as a regulator of cardiac remodeling and hypertrophy. PMID:17569887

  9. Activin A Predicts Left Ventricular Remodeling and Mortality in Patients with ST-Elevation Myocardial Infarction

    PubMed Central

    Lin, Jeng-Feng; Hsu, Shun-Yi; Teng, Ming-Sheng; Wu, Semon; Hsieh, Chien-An; Jang, Shih-Jung; Liu, Chih-Jen; Huang, Hsuan-Li; Ko, Yu-Lin

    2016-01-01

    Background Activin A levels increase in a variety of heart diseases including ST-elevation myocardial infarction (STEMI). The aim of this study is to investigate whether the level of activin A can be beneficial in predicting left ventricular remodeling, heart failure, and death in patients with ST-elevation myocardial infarction (STEMI). Methods We enrolled 278 patients with STEMI who had their activin A levels measured on day 2 of hospitalization. Echocardiographic studies were performed at baseline and were repeated 6 months later. Thereafter, the clinical events of these patients were followed for a maximum of 3 years, including all-cause death and readmission for heart failure. Results During hospitalization, higher activin A level was associated with higher triglyceride level, lower left ventricular ejection fraction (LVEF), and lower left ventricular end diastolic ventricular volume index (LVEDVI) in multivariable linear regression model. During follow-up, patients with activin A levels > 129 pg/ml had significantly lower LVEF, and higher LVEDVI at 6 months. Kaplan-Meier survival curves showed that activin A level > 129 pg/ml was a predictor of all-cause death (p = 0.022), but not a predictor of heart failure (p = 0.767). Conclusions Activin A level > 129 pg/ml predicts worse left ventricular remodeling and all-cause death in STEMI. PMID:27471355

  10. Vascular and right ventricular remodelling in chronic thromboembolic pulmonary hypertension.

    PubMed

    Delcroix, Marion; Vonk Noordegraaf, Anton; Fadel, Elie; Lang, Irene; Simonneau, Gérald; Naeije, Robert

    2013-01-01

    In chronic thromboembolic pulmonary hypertension (CTEPH) increased pulmonary vascular resistance is caused by fibrotic organisation of unresolved thromboemboli. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration, although distal arteriopathy can be observed as a consequence of non-occluded area over-perfusion. Accordingly, there is proportionally more wave reflection in CTEPH, impacting on pressure and flow wave morphology. However, the time constant, i.e. resistance × compliance, is not different in CTEPH and PAH, indicating only trivial effects of proximal wave reflection on hydraulic right ventricular load. More discriminative is the analysis of the pressure decay after pulmonary arterial occlusion, which is more rapid in the absence of significant distal arteriopathy. Structure and function of the right ventricle show a similar pattern to right ventricular hypertrophy, namely dilatation and wall thickening, as well as loss of function in CTEPH and PAH. This is probably related to similar loading conditions. Hyperventilation with hypocapnia is characteristic of both PAH and CTEPH. Ventilatory equivalents for carbon dioxide, as a function of arterial carbon dioxide tension, conform to the alveolar ventilation equation in both conditions, indicating a predominant role of increased chemosensitivity. However, a slight increase in the arterial to end-tidal carbon dioxide tension gradient in CTEPH shows a contribution of increased dead space ventilation. PMID:22903956

  11. Moderate mitral regurgitation accelerates left ventricular remodeling after postero-lateral myocardial infarction

    PubMed Central

    Soleimani, Mehrdad; Khazalpour, Michael; Cheng, Guangming; Zhang, Zhihong; Acevedo-Bolton, Gabriel; Saloner, David A.; Mishra, Rakesh; Wallace, Arthur W.; Guccione, Julius M.; Ge, Liang; Ratcliffe, Mark B.

    2012-01-01

    Background Chronic ischemic mitral regurgitation (CIMR: MR) is associated with poor outcome. However, the effect of CIMR on left ventricular (LV) remodeling after postero-lateral myocardial infarction (MI) remains controversial. We tested the hypothesis that moderate MR accelerates LV remodeling after postero-lateral MI. Methods/Results Postero-lateral MI was created in 10 sheep. Cardiac MRI was performed 2 weeks before and 2, 8 and 16 weeks after MI. LV and right ventricular (RV) volumes were measured and regurgitant volume (RegurgVolume) calculated as the difference between LV and RV stroke volumes. Multivariate mixed effect regression showed that LV volumes at end-diastole (ED) and end-systole (ES) and LV sphericity were strongly correlated with both RegurgVolume (p<0.0001, p=0.0086 and p=0.0007 respectively) and %Infarct area (p=0.0156, 0=0.0307, and p<0.0001 respectively). On the other hand, while LV hypertrophy (LV wall volume) increased from 2 to 16 weeks post-MI there was no effect of either RegurgVolume or %Infarct. Conclusions Moderate mitral regurgitation accelerates LV remodeling after postero-lateral MI. Further studies are needed to determine whether mitral valve repair is able to slow or reverse MI remodeling after postero-lateral MI. PMID:21945222

  12. The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure

    PubMed Central

    Bae, Hyun Kyung; Lee, Hyeryon; Kim, Kwan Chang

    2016-01-01

    Purpose Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF. Methods The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed. Results The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-α, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4. Conclusion Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function. PMID:27462355

  13. Roles of ghrelin in left-ventricular remodelling after acute myocardial infarction

    PubMed Central

    Kondo, Hideyuki; Hojo, Yukihiro; Takahashi, Nozomu; Ikemoto, Tomokazu; Aoki, Hirotaka; Dezaki, Katsuya; Kario, Kazuomi; Katsuki, Takaaki; Yada, Toshihiko; Shimada, Kazuyuki

    2010-01-01

    Objective The purpose of this study was to elucidate the role of ghrelin after acute myocardial infarction (AMI) in left ventricular (LV) remodelling. Design Prospective observational study. Setting Jichi Medical University Hospital. Patients Fifty consecutive patients experiencing their first AMI. Interventions Ghrelin was measured on the day of admission, day 7, day 14 and 6 months after AMI. Patients were treated by percutaneous coronary intervention, and successful myocardial reperfusion was accomplished within 12 h after onset. To analyse LV remodelling, the authors performed left ventriculographies on the day of admission and 6 months after AMI. Main outcome measures Changes in LV volume. Results Plasma ghrelin increased significantly after AMI (admission: 40.9±7.3; day 7: 89.5±11.0; day 14: 92.6±11.8 fmol/ml, p<0.0001). There was a significant correlation between ghrelin on day 14 and changes in LV volume over 6 months (r=+0.46, p<0.001). Multivariate regression analysis showed that ghrelin on day 14 is a significant predictor of LV remodelling after AMI (β=+0.44, p=0.001). Conclusion To our knowledge, this is the first report that shows a relation between circulating ghrelin after AMI and the progression of LV remodelling in the chronic phase. The elevation of ghrelin after AMI might be a compensatory mechanism to attenuate LV remodelling.

  14. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms

    PubMed Central

    Liu, Yonggang; Goodson, Jamie M.; Zhang, Bo; Chin, Michael T.

    2015-01-01

    Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation. PMID:26042051

  15. Atorvastatin Therapy during the Peri-Infarct Period Attenuates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction

    PubMed Central

    Sato, Hiroshi; Bi, Qiuli; Hunt, Greg; Vincent, Robert J.; Peng, Yong; Shirk, Gregg; Dawn, Buddhadeb; Bolli, Roberto

    2011-01-01

    Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dtmax, end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) and lower LV end-diastolic pressure (LVEDP). Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis. PMID:21980426

  16. Remote Zone Extracellular Volume and Left Ventricular Remodeling in Survivors of ST-Elevation Myocardial Infarction

    PubMed Central

    Carberry, Jaclyn; Carrick, David; Haig, Caroline; Rauhalammi, Samuli M.; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, Mitchell; Davie, Andrew; Mahrous, Ahmed; Ford, Ian; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Oldroyd, Keith G.

    2016-01-01

    The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; P<0.001). In multivariable regression, left ventricular ejection fraction was inversely associated with remote zone ECV (P<0.001), and diabetes mellitus was positively associated with remote zone ECV (P=0.010). No ST-segment resolution (P=0.034) and extent of ischemic area at risk (P<0.001) were multivariable associates of the change in remote zone ECV at 6 months (ΔECV). ΔECV was a multivariable associate of the change in left ventricular end-diastolic volume at 6 months (regression coefficient [95% confidence interval]: 1.43 (0.10–2.76); P=0.036). ΔECV is implicated in the pathophysiology of left ventricular remodeling post STEMI, but because the effect size is small, ΔECV has limited use as a clinical biomarker of remodeling. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT02072850. PMID:27354423

  17. Dilation and Hypertrophy: A Cell-Based Continuum Mechanics Approach Towards Ventricular Growth and Remodeling

    NASA Astrophysics Data System (ADS)

    Ulerich, J.; Göktepe, S.; Kuhl, E.

    This manuscript presents a continuum approach towards cardiac growth and remodeling that is capable to predict chronic maladaptation of the heart in response to changes in mechanical loading. It is based on the multiplicative decomposition of the deformation gradient into and elastic and a growth part. Motivated by morphological changes in cardiomyocyte geometry, we introduce an anisotropic growth tensor that can capture both hypertrophic wall thickening and ventricular dilation within one generic concept. In agreement with clinical observations, we propose wall thickening to be a stress-driven phenomenon whereas dilation is introduced as a strain-driven process. The features of the proposed approach are illustrated in terms of the adaptation of thin heart slices and in terms overload-induced dilation in a generic bi-ventricular heart model.

  18. Left ventricular reverse remodeling after transcatheter aortic valve implantation: a cardiovascular magnetic resonance study

    PubMed Central

    2013-01-01

    Background In patients with severe aortic stenosis, left ventricular hypertrophy is associated with increased myocardial stiffness and dysfunction linked to cardiac morbidity and mortality. We aimed at systematically investigating the degree of left ventricular mass regression and changes in left ventricular function six months after transcatheter aortic valve implantation (TAVI) by cardiovascular magnetic resonance (CMR). Methods Left ventricular mass indexed to body surface area (LVMi), end diastolic volume indexed to body surface area (LVEDVi), left ventricular ejection fraction (LVEF) and stroke volume (SV) were investigated by CMR before and six months after TAVI in patients with severe aortic stenosis and contraindications for surgical aortic valve replacement. Results Twenty-sevent patients had paired CMR at baseline and at 6-month follow-up (N=27), with a mean age of 80.7±5.2 years. LVMi decreased from 84.5±25.2 g/m2 at baseline to 69.4±18.4 g/m2 at six months follow-up (P<0.001). LVEDVi (87.2±30.1 ml /m2vs 86.4±22.3 ml/m2; P=0.84), LVEF (61.5±14.5% vs 65.1±7.2%, P=0.08) and SV (89.2±22 ml vs 94.7±26.5 ml; P=0.25) did not change significantly. Conclusions Based on CMR, significant left ventricular reverse remodeling occurs six months after TAVI. PMID:23692630

  19. Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling in Infants with Single Ventricle

    PubMed Central

    Mital, Seema; Chung, Wendy K.; Colan, Steven D.; Sleeper, Lynn A.; Manlhiot, Cedric; Arrington, Cammon B.; Cnota, James F.; Graham, Eric M.; Mitchell, Michael E.; Goldmuntz, Elizabeth; Li, Jennifer S.; Levine, Jami C.; Lee, Teresa M.; Margossian, Renee; Hsu, Daphne T.

    2011-01-01

    Background We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function and response to enalapril in infants with single ventricle. Methods and Results Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with RAAS upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate (eGFR), and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high-risk), and those with <2 homozygous risk genotypes (low-risk) at two time points - before the superior-cavopulmonary-connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: 38 were high-risk, 116 were low-risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and eGFR increased after SCPC in the low-risk (p<0.05) but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline and height remained lower in the high-risk group at 14 months especially in those receiving enalapril (p<0.05). Conclusions RAAS-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. RAAS genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume unloading surgery. Follow-up is warranted to assess longterm impact. Clinical Trial Registration Clinical Trials.gov Identifier NCT00113087 PMID:21576655

  20. Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model.

    PubMed

    Aguero, Jaume; Ishikawa, Kiyotake; Hadri, Lahouaria; Santos-Gallego, Carlos; Fish, Kenneth; Hammoudi, Nadjib; Chaanine, Antoine; Torquato, Samantha; Naim, Charbel; Ibanez, Borja; Pereda, Daniel; García-Alvarez, Ana; Fuster, Valentin; Sengupta, Partho P; Leopold, Jane A; Hajjar, Roger J

    2014-10-15

    In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca(2+)-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism. PMID:25158063

  1. Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

    PubMed Central

    Wu, Aiming; Zhai, Jianying; Zhang, Dongmei; Lou, Lixia; Zhu, Haiyan; Gao, Yonghong; Chai, Limin; Xing, Yanwei; Lv, Xiying; Zhu, Lingqun; Zhao, Mingjing; Wang, Shuoren

    2013-01-01

    Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI). Methods. Male Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group) with sample size (n) of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion). Wenxin Granule (1.35 g/kg/day), metoprolol (12 mg/kg/day), and distilled water (5 mL/kg/day for the control and model groups) were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E) dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Serum angiotensin II (Ang II) concentration was measured using the enzyme-linked immunosorbent assay (ELISA). Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI. Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI. PMID:23997803

  2. Nocturnal Blood Pressure Pattern Affects Left Ventricular Remodeling and Late Gadolinium Enhancement in Patients with Hypertension and Left Ventricular Hypertrophy

    PubMed Central

    Yokota, Hajime; Imai, Yasuko; Tsuboko, Yusuke; Tokumaru, Aya M.; Fujimoto, Hajime; Harada, Kazumasa

    2013-01-01

    Background Left ventricular hypertrophy (LVH) is an independent predictor of cardiac mortality, regardless of its etiology. Previous studies have shown that high nocturnal blood pressure (BP) affects LV geometry in hypertensive patients. It has been suggested that continuous pressure overload affects the development of LVH, but it is unknown whether persistent pressure influences myocardial fibrosis or whether the etiology of LVH is associated with myocardial fibrosis. Comprehensive cardiac magnetic resonance (CMR) including the late gadolinium enhancement (LGE) technique can evaluate both the severity of changes in LV geometry and myocardial fibrosis. We tested the hypothesis that the nocturnal non-dipper BP pattern causes LV remodeling and fibrosis in patients with hypertension and LVH. Methods Forty-seven hypertensive patients with LVH evaluated by echocardiography (29 men, age 73.0±10.4 years) were examined by comprehensive CMR and 24-h ambulatory blood pressure monitoring (ABPM). Results and Conclusions Among the 47 patients, twenty-four had nocturnal non-dipper BP patterns. Patients with nocturnal non-dipper BP patterns had larger LV masses and scar volumes independent of etiologies than those in patients with dipper BP patterns (p = 0.035 and p = 0.015, respectively). There was no significant difference in mean 24-h systolic BP between patients with and without nocturnal dipper BP patterns (p = 0.367). Among hypertensive patients with LVH, the nocturnal non-dipper blood pressure pattern is associated with both LV remodeling and myocardial fibrosis independent of LVH etiology. PMID:23840777

  3. Muscle RING Finger-1 Promotes a Maladaptive Phenotype in Chronic Hypoxia-Induced Right Ventricular Remodeling

    PubMed Central

    Campen, Matthew J.; Paffett, Michael L.; Colombo, E. Sage; Lucas, Selita N.; Anderson, Tamara; Nysus, Monique; Norenberg, Jeffrey P.; Gershman, Ben; Hesterman, Jacob; Hoppin, Jack; Willis, Monte

    2014-01-01

    Exposure to chronic hypoxia (CH) induces elevated pulmonary artery pressure/resistance, leading to an eventual maladaptive right ventricular hypertrophy (RVH). Muscle RING finger-1 (MuRF1) is a muscle-specific ubiquitin ligase that mediates myocyte atrophy and has been shown to play a role in left ventricular hypertrophy and altered cardiac bioenergetics in pressure overloaded hearts. However, little is known about the contribution of MuRF1 impacting RVH in the setting of CH. Therefore, we hypothesized that MuRF1 deletion would enhance RVH compared to their wild-type littermates, while cardiac-specific overexpression would reduce hypertrophy following CH-induced pulmonary hypertension. We assessed right ventricular systolic pressure (RVSP), right ventricle to left ventricle plus septal weight ratio (RV/LV+S) and hematocrit (Hct) following a 3-wk isobaric CH exposure. Additionally, we conducted dual-isotope SPECT/CT imaging with cardiac function agent 201Tl-chloride and cell death agent 99mTc-annexin V. Predictably, CH induced pulmonary hypertension, measured by increased RVSP, RV/LV+S and Hct in WT mice compared to normoxic WT mice. Normoxic WT and MuRF1-null mice exhibited no significant differences in RVSP, RV/LV+S or Hct. CH-induced increases in RVSP were also similar between WT and MuRF1-null mice; however, RV/LV+S and Hct were significantly elevated in CH-exposed MuRF1-null mice compared to WT. In cardiac-specific MuRF1 overexpressing mice, RV/LV+S increased significantly due to CH exposure, even greater than in WT mice. This remodeling appeared eccentric, maladaptive and led to reduced systemic perfusion. In conclusion, these results are consistent with an atrophic role for MuRF1 regulating the magnitude of right ventricular hypertrophy following CH-induction of pulmonary hypertension. PMID:24811453

  4. Muscle RING finger-1 promotes a maladaptive phenotype in chronic hypoxia-induced right ventricular remodeling.

    PubMed

    Campen, Matthew J; Paffett, Michael L; Colombo, E Sage; Lucas, Selita N; Anderson, Tamara; Nysus, Monique; Norenberg, Jeffrey P; Gershman, Ben; Hesterman, Jacob; Hoppin, Jack; Willis, Monte

    2014-01-01

    Exposure to chronic hypoxia (CH) induces elevated pulmonary artery pressure/resistance, leading to an eventual maladaptive right ventricular hypertrophy (RVH). Muscle RING finger-1 (MuRF1) is a muscle-specific ubiquitin ligase that mediates myocyte atrophy and has been shown to play a role in left ventricular hypertrophy and altered cardiac bioenergetics in pressure overloaded hearts. However, little is known about the contribution of MuRF1 impacting RVH in the setting of CH. Therefore, we hypothesized that MuRF1 deletion would enhance RVH compared to their wild-type littermates, while cardiac-specific overexpression would reduce hypertrophy following CH-induced pulmonary hypertension. We assessed right ventricular systolic pressure (RVSP), right ventricle to left ventricle plus septal weight ratio (RV/LV+S) and hematocrit (Hct) following a 3-wk isobaric CH exposure. Additionally, we conducted dual-isotope SPECT/CT imaging with cardiac function agent 201Tl-chloride and cell death agent 99mTc-annexin V. Predictably, CH induced pulmonary hypertension, measured by increased RVSP, RV/LV+S and Hct in WT mice compared to normoxic WT mice. Normoxic WT and MuRF1-null mice exhibited no significant differences in RVSP, RV/LV+S or Hct. CH-induced increases in RVSP were also similar between WT and MuRF1-null mice; however, RV/LV+S and Hct were significantly elevated in CH-exposed MuRF1-null mice compared to WT. In cardiac-specific MuRF1 overexpressing mice, RV/LV+S increased significantly due to CH exposure, even greater than in WT mice. This remodeling appeared eccentric, maladaptive and led to reduced systemic perfusion. In conclusion, these results are consistent with an atrophic role for MuRF1 regulating the magnitude of right ventricular hypertrophy following CH-induction of pulmonary hypertension. PMID:24811453

  5. Aldehyde dehydrogenase 2 activation in heart failure restores mitochondrial function and improves ventricular function and remodelling

    PubMed Central

    Gomes, Katia M.S.; Campos, Juliane C.; Bechara, Luiz R.G.; Queliconi, Bruno; Lima, Vanessa M.; Disatnik, Marie-Helene; Magno, Paulo; Chen, Che-Hong; Brum, Patricia C.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

    2014-01-01

    Aims We previously demonstrated that pharmacological activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects the heart against acute ischaemia/reperfusion injury. Here, we determined the benefits of chronic activation of ALDH2 on the progression of heart failure (HF) using a post-myocardial infarction model. Methods and results We showed that a 6-week treatment of myocardial infarction-induced HF rats with a selective ALDH2 activator (Alda-1), starting 4 weeks after myocardial infarction at a time when ventricular remodelling and cardiac dysfunction were present, improved cardiomyocyte shortening, cardiac function, left ventricular compliance and diastolic function under basal conditions, and after isoproterenol stimulation. Importantly, sustained Alda-1 treatment showed no toxicity and promoted a cardiac anti-remodelling effect by suppressing myocardial hypertrophy and fibrosis. Moreover, accumulation of 4-hydroxynonenal (4-HNE)-protein adducts and protein carbonyls seen in HF was not observed in Alda-1-treated rats, suggesting that increasing the activity of ALDH2 contributes to the reduction of aldehydic load in failing hearts. ALDH2 activation was associated with improved mitochondrial function, including elevated mitochondrial respiratory control ratios and reduced H2O2 release. Importantly, selective ALDH2 activation decreased mitochondrial Ca2+-induced permeability transition and cytochrome c release in failing hearts. Further supporting a mitochondrial mechanism for ALDH2, Alda-1 treatment preserved mitochondrial function upon in vitro aldehydic load. Conclusions Selective activation of mitochondrial ALDH2 is sufficient to improve the HF outcome by reducing the toxic effects of aldehydic overload on mitochondrial bioenergetics and reactive oxygen species generation, suggesting that ALDH2 activators, such as Alda-1, have a potential therapeutic value for treating HF patients. PMID:24817685

  6. Beneficial effect of simvastatin and pravastatin treatment on adverse cardiac remodelling and glomeruli loss in spontaneously hypertensive rats.

    PubMed

    Bezerra, Daniele G; Mandarim-de-Lacerda, Carlos A

    2005-04-01

    The aim of the present study was to investigate the possibility of different effects of the hydrophobic statin simvastatin and the hydrophilic statin pravastatin on the remodelling process in the overloaded left ventricle and renal cortex of SHRs (spontaneously hypertensive rats). Fifteen SHRs were treated for 40 days with simvastatin, pravastatin or placebo (water) via orogastric administration. Left ventricle and renal cortex were examined by light microscopy and stereology. LV (left ventricular) cardiomyocyte nuclei (N[cmn]) and glomeruli (N[gl]) numbers were estimated by the dissector method. BP (blood pressure) and serum triacylglycerols (triglycerides) were lower in the statin-treated groups than in the untreated control group. The volume density of the interstitial connective tissue was smaller and length density of the intramyocardial arteries, as well as the arteries/cardiomyocyte ratio, was greater in the statin-treated groups than in the control group. No difference was observed between the two statin-treated groups. The cross-sectional cardiomyocyte area was significantly smaller in the simvastatin-treated group than in the control or pravastatin-treated groups, and it was smaller in the pravastatin-treated group than in the control group. N[cmn] and N[gl] were greater in the two statin-treated groups than in the control group, but no significant difference was observed between the two statin-treated groups. In conclusion, administration of the statins simvastatin and pravastatin to SHRs effectively prevented the elevation in BP and serum triaclyglycerols, and also attenuated adverse cardiac and kidney remodelling by preventing LV hypertrophy, enhancing myocardial vascularization with the decrease in interstitial fibrosis and attenuating cardiomyocyte and glomerular loss. PMID:15610072

  7. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction.

    PubMed

    Huang, Yan; Wang, Dandan; Wang, Xin; Zhang, Yijie; Liu, Tao; Chen, Yuting; Tang, Yanhong; Wang, Teng; Hu, Dan; Huang, Congxin

    2016-01-01

    CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling. PMID:27585634

  8. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction

    PubMed Central

    Huang, Yan; Wang, Dandan; Wang, Xin; Zhang, Yijie; Liu, Tao; Chen, Yuting; Tang, Yanhong; Wang, Teng; Hu, Dan; Huang, Congxin

    2016-01-01

    CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling. PMID:27585634

  9. Remodeling of Glucose Metabolism Precedes Pressure Overload -Induced Left Ventricular Hypertrophy: Review of a Hypothesis

    PubMed Central

    Kundu, Bijoy K.; Zhong, Min; Sen, Shiraj; Davogustto, Giovanni; Keller, Susanna R.; Taegtmeyer, Heinrich

    2015-01-01

    When subjected to pressure overload, the ventricular myocardium shifts from fatty acids to glucose as its main source for energy provision and frequently increases its mass. Here, we review the evidence in support of the concept that metabolic remodeling, measured as increased myocardial glucose uptake using dynamic positron emission tomography (PET) with the glucose analogue 2-deoxy-2-[18F]-fluoro-D-glucose (FDG), precedes the onset of left ventricular hypertrophy (LVH) and heart failure. Consistent with this, early intervention with propranolol, which attenuates glucose uptake, prevents the maladaptive metabolic response and preserves cardiac function in vivo. We also review ex vivo studies suggesting a link between dysregulated myocardial glucose metabolism, intracellular accumulation of glucose 6-phosphate (G6P) and contractile dysfunction of the heart. G6P levels correlate with activation of mTOR (mechanistic target of rapamycin) and endoplasmic reticulum stress. This sequence of events could be prevented by pre-treatment with rapamycin (mTOR inhibition) or metformin (enzyme 5′-AMP-activated protein kinase activation ). In conclusion, we propose that metabolic imaging with FDG PET may provide a novel approach to guide the treatment of patients with hypertension-induced LVH. PMID:25791172

  10. Fibroblast Growth Factor-9 Enhances M2 Macrophage Differentiation and Attenuates Adverse Cardiac Remodeling in the Infarcted Diabetic Heart

    PubMed Central

    Singla, Dinender K.; Singla, Reetu D.; Abdelli, Latifa S.; Glass, Carley

    2015-01-01

    Inflammation has been implicated as a perpetrator of diabetes and its associated complications. Monocytes, key mediators of inflammation, differentiate into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon infiltration of damaged tissue. However, the inflammatory cell types, which propagate diabetes progression and consequential adverse disorders, remain unclear. The current study was undertaken to assess monocyte infiltration and the role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage differentiation and cardioprotection in the diabetic infarcted heart. Db/db diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9 groups. MI was induced by permanent coronary artery ligation and animals were subjected to 2D transthoracic echocardiography two weeks post-surgery. Immunohistochemical and immunoassay results from heart samples collected suggest significantly increased infiltration of monocytes (Mean ± SEM; MI: 2.02% ± 0.23% vs. Sham 0.75% ± 0.07%; p<0.05) and associated pro-inflammatory cytokines (TNF-α, MCP-1, and IL-6), adverse cardiac remodeling (Mean ± SEM; MI: 33% ± 3.04% vs. Sham 2.2% ± 0.33%; p<0.05), and left ventricular dysfunction (Mean ± SEM; MI: 35.4% ± 1.25% vs. Sham 49.19% ± 1.07%; p<0.05) in the MI group. Importantly, treatment of diabetic infarcted myocardium with FGF-9 resulted in significantly decreased monocyte infiltration (Mean ± SEM; MI+FGF-9: 1.39% ± 0.1% vs. MI: 2.02% ± 0.23%; p<0.05), increased M2 macrophage differentiation (Mean ± SEM; MI+FGF-9: 4.82% ± 0.86% vs. MI: 0.85% ± 0.3%; p<0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean ± SEM; MI+FGF-9: 11.59% ± 1.2% vs. MI: 33% ± 3.04%; p<0.05), and improved cardiac function (Fractional shortening, Mean ± SEM; MI+FGF-9: 41.51% ± 1.68% vs. MI: 35.4% ± 1.25%; p<0.05). In conclusion, our data suggest FGF-9 possesses novel therapeutic potential in its ability to

  11. Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.

    PubMed

    Beaumont, Eric; Southerland, Elizabeth M; Hardwick, Jean C; Wright, Gary L; Ryan, Shannon; Li, Ying; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

    2015-10-01

    This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID:26276818

  12. An Adverse Electrophysiological Interaction Between an Implantable Cardioverter-Defibrillator and a Ventricular Assist Device.

    PubMed

    Chhabra, Lovely; Hiendlmayr, Brett; Kluger, Jeffrey

    2015-01-01

    Many patients with left ventricular assist devices (LVAD) have implantable cardioverter defibrillators (ICDs) as part of the management of advanced heart failure. With increasing use and coexistence of these devices in patients with advanced cardiomyopathy, adverse interactions between these devices have been recognized. We herewith describe a rare adverse interaction of electromagnetic interference (EMI) between a third-generation, continuous-flow device (The HeartWare HVAD) and an ICD which resulted in the delivery of inappropriate ICD therapies. A schematic approach for the prevention and treatment of electromagnetic interference has also been described. PMID:26263716

  13. Heterogeneous fate of perfusion and contraction after anterior wall acute myocardial infarction and effects on left ventricular remodeling.

    PubMed

    Marcassa, C; Galli, M; Bolli, R; Temporelli, P L; Campini, R; Giannuzzi, P

    1998-12-15

    After acute myocardial infarction, patency of infarct vessel and extent of left venticular (LV) dysfunction are major determinants of ventricular remodeling. Spontaneous, delayed reperfusion in the infarct zone occurs in a sizeable number of patients well after the subacute phase. The aim of this study was to determine the relation between the occurrence of this spontaneous, delayed reperfusion and LV remodeling. In 84 patients, resting LV volumes, topography, regional function, and perfusion were quantitatively evaluated by 2-dimensional echocardiography and sestamibi tomography 5 weeks (study 1) and 7 months (study 2) after anterior Q-wave infarction. At study 2, LV end-diastolic volume increased by > 15% in 17 patients (20%, LV remodeling); they had already had at study 1 significantly larger LV volumes, more severe hypoperfusion and wall motion abnormalities, and greater regional dilation than patients with stable LV volumes. Delayed reperfusion occurred in 8 of 17 patients with and in 42 of 67 patients without LV remodeling (47% vs 63%; p=NS). At study 2, LV regional dilation and end-diastolic volumes were stable in patients with, but increased in patients without, spontaneous reperfusion (from 25+/-24% to 29+/-26% at study 2 [p<0.05] and from 65+/-14 to 68+/-18 ml/m2 [p <0.05]). At multivariate analysis, however, regional ventricular dilation at study 1 was the sole predictor of further LV remodeling. Thus, after acute myocardial infarction, spontaneous reperfusion occurring after 5 weeks plays only a minor role in influencing LV remodeling. Benefits from delayed reperfusion seem limited to patients with preserved LV volumes; patients with an enlarged left ventricle 5 weeks after acute infarction are prone to further LV remodeling, irrespective of delayed reperfusion. PMID:9874047

  14. Ataxia telangiectasia-mutated kinase deficiency exacerbates left ventricular dysfunction and remodeling late after myocardial infarction.

    PubMed

    Daniel, Laura L; Scofield, Stephanie L C; Thrasher, Patsy; Dalal, Suman; Daniels, Christopher R; Foster, Cerrone R; Singh, Mahipal; Singh, Krishna

    2016-08-01

    Ataxia telangiectasia-mutated kinase (ATM), a cell cycle checkpoint protein, is activated in response to DNA damage and oxidative stress. We have previously shown that ATM deficiency is associated with increased apoptosis and fibrosis and attenuation of cardiac dysfunction early (1-7 days) following myocardial infarction (MI). Here, we tested the hypothesis that enhanced fibrosis and apoptosis, as observed early post-MI during ATM deficiency, exacerbate cardiac dysfunction and remodeling in ATM-deficient mice late post-MI. MIs were induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery. Left ventricular (LV) structural and functional parameters were assessed by echocardiography 14 and 28 days post-MI, whereas biochemical parameters were measured 28 days post-MI. hKO-MI mice exhibited exacerbated LV dysfunction as observed by increased LV end-systolic volume and decreased percent fractional shortening and ejection fraction. Infarct size and thickness were not different between the two genotypes. Myocyte cross-sectional area was greater in hKO-MI group. The hKO-MI group exhibited increased fibrosis in the noninfarct and higher expression of α-smooth muscle actin (myofibroblast marker) in the infarct region. Apoptosis and activation of GSK-3β (proapoptotic kinase) were significantly lower in the infarct region of hKO-MI group. Matrix metalloproteinase 2 (MMP-2) expression was not different between the two genotypes. However, MMP-9 expression was significantly lower in the noninfarct region of hKO-MI group. Thus ATM deficiency exacerbates cardiac remodeling late post-MI with effects on cardiac function, fibrosis, apoptosis, and myocyte hypertrophy. PMID:27288435

  15. Visceral Adiposity and Left Ventricular Remodeling: the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Abbasi, Siddique A.; Hundley, W. Gregory; Bluemke, David A.; Blankstein, Ron; Jerosch-Herold, Michael; Lima, Joao A.C.; Allison, Matthew A.; Murthy, Venkatesh L.; Shah, Ravi V.

    2015-01-01

    Background and Aims Visceral fat (VF) is a source of pro-inflammatory adipokines implicated in cardiac remodeling. We sought to determine the impact of visceral fat (VF) and subcutaneous fat (SQ) depots on left ventricular (LV) structure, function, and geometry in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods and Results We performed a post-hoc analysis on 1,151 participants from MESA with cardiac magnetic resonance quantification of LV mass and LV mass-to-volume ratio (LVMV, an index of concentricity) and computed tomographic-derived SQ and VF area. Multivariable regression models to estimate association between height-indexed SQ and VF area (per cm2/m) with height-indexed LV mass (per height2.7) and LVMV were constructed, adjusted for clinical, biochemical, and demographic covariates. We found that both VF and SQ area were associated with height-indexed LV mass (ρ =0.36 and 0.12, P<0.0001, respectively), while only VF area was associated with LVMV (ρ =0.28, P<0.0001). Individuals with above-median VF had lower LV ejection fraction, greater indexed LV volumes and mass, and higher LVMV (all P < 0.001). In multivariable models adjusted for weight, VF (but not SQ) area was associated with LV concentricity and LV mass index, across both sexes. Conclusion Visceral adiposity is independently associated with LV concentricity, a precursor to heart failure. Further study into the role of VF in LV remodeling as a potential therapeutic target is warranted. PMID:26033394

  16. Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

    PubMed

    Liu, Xiaoli; Pachori, Alok S; Ward, Christopher A; Davis, J Paul; Gnecchi, Massimiliano; Kong, Deling; Zhang, Lunan; Murduck, Jared; Yet, Shaw-Fang; Perrella, Mark A; Pratt, Richard E; Dzau, Victor J; Melo, Luis G

    2006-02-01

    We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarction recovery has not been investigated. In the current study, we assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV) remodeling and function using echocardiographic imaging and histomorphometric approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11) particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene transfer, the animals were subjected to 30 min of ischemia by ligation of left anterior descending artery (LAD) followed by reperfusion. Echocardiographic measurements were obtained in a blinded fashion prior and at 1.5 and 3 months after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ groups, respectively at 1.5 months after MI. Three months after MI, EF recovered fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV dimensions were markedly increased and the anterior wall was markedly thinned in the LacZ-treated animals compared with the HO-1-treated animals. Significant myocardial scarring and fibrosis were observed in the LacZ-group in association with elevated levels of interstitial collagen I and III and MMP-2 activity. Post-MI myofibroblast accumulation was reduced in the HO-1-treated animals, and retroviral overexpression of HO-1 reduced proliferation of isolated cardiac fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces fibrosis and ventricular remodeling and restores LV function and chamber dimensions after myocardial infarction. PMID:16449792

  17. Effect of Right Ventricular versus Biventricular Pacing on Electrical Remodeling in the Normal Heart

    PubMed Central

    Saba, Samir; Mehdi, Haider; Mathier, Michael A.; Islam, M. Zahadul; Salama, Guy; London, Barry

    2010-01-01

    Background Biventricular (BIV) pacing can improve cardiac function in heart failure by altering the mechanical and electrical substrates. We investigated the effect of BIV versus right ventricular (RV) pacing on the normal heart. Methods and Results Male New Zealand White rabbits (n=33) were divided into 3 groups: sham-operated (control), RV pacing, and BIV pacing groups. Four weeks after surgery, the native QT (p=0.004) interval was significantly shorter in the BIV group compared to the RV or sham-operated groups. Also, compared to rabbits in the RV group, rabbits in the BIV group had shorter RV ventricular effective refractory period (VERP) at all cycle lengths, and shorter LV paced QT interval during the drive train of stimuli and close to refractoriness (p<0.001 for all comparisons). Protein expression of the KVLQT1 was significantly increased in the BIV group compared to the RV and control groups, while protein expression of SCN5A and connexin43 was significantly decreased in the RV compared to the other study groups. Erg protein expression was significantly increased in both pacing groups compared to the controls. Conclusions In this rabbit model, we demonstrate a direct effect of BIV but not RV pacing on shortening the native QT interval as well as the paced QT interval during burst pacing and close to the VERP. These findings underscore the fact that the effect of BIV pacing is partially mediated through direct electrical remodeling and may have implications as to the effect of BIV pacing on arrhythmia incidence and burden. PMID:20042767

  18. Hypercholesterolaemia exacerbates ventricular remodelling after myocardial infarction in the rat: role of angiotensin II type 1 receptors

    PubMed Central

    Mączewski, M; Mączewska, J; Duda, M

    2008-01-01

    Background and purpose: Diet-induced hypercholesterolaemia exacerbates post-myocardial infarction (MI) ventricular remodelling and heart failure, but the mechanism of this phenomenon remains unknown. This study examined whether worsening of post-MI ventricular remodelling induced by dietary hypercholesterolaemia was related to upregulation of angiotensin II type 1 (AT1) receptor in the rat heart. Experimental approach: MI was induced surgically in rats fed normal or high cholesterol diet. Both groups of rats were then assigned to control, atorvastatin, losartan or atorvastatin+losartan-treated subgroups and followed for 8 weeks. Left ventricular (LV) function was assessed with echocardiography. In isolated hearts, LV pressures were measured with a latex balloon and a tip catheter. AT1-receptor density was assessed in LV membranes with radioligand-binding assays. Key results: High cholesterol diet exacerbated LV dilation and dysfunction in post-MI hearts. Atorvastatin or losartan prevented these hypercholesterolaemia-induced effects, whereas their combination was not more effective than each drug alone. AT1 receptors were upregulated 8 weeks after MI, this was further increased by hypercholesterolaemia and restored to baseline levels by atorvastatin. Conclusions and implications: Hypercholesterolaemia exacerbated LV remodelling and dysfunction in post-MI rat hearts and upregulated cardiac AT1 receptors. All these effects were effectively prevented by atorvastatin. Thus, the pleiotropic statin effects may include interference with the renin-angiotensin system through downregulation of AT1 receptors. PMID:18536757

  19. IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction

    PubMed Central

    Tejada, Thor; Tan, Lin; Torres, Rebecca A.; Calvert, John W.; Lambert, Jonathan P.; Zaidi, Madiha; Husain, Murtaza; Berce, Maria D.; Naib, Hussain; Pejler, Gunnar; Abrink, Magnus; Graham, Robert M.; Lefer, David J.; Naqvi, Nawazish; Husain, Ahsan

    2016-01-01

    Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in postischemic heart disease. PMID:27274047

  20. Nicorandil Prevents Right Ventricular Remodeling by Inhibiting Apoptosis and Lowering Pressure Overload in Rats with Pulmonary Arterial Hypertension

    PubMed Central

    Yu, Yan-Zhe; Wang, Hui; Bi, Li-Qing; Xie, Wei-Ping; Wang, Hong

    2012-01-01

    Background Most of the deaths among patients with severe pulmonary arterial hypertension (PAH) are caused by progressive right ventricular (RV) pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. Methodology/Principal Findings RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT). RV systolic pressure (RVSP) was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP) ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD) reversed these beneficial effects of nicorandil in MCT-injected rats. Conclusions/Significance Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K+ (mitoKATP) channels. The use of a mitoKATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV remodeling during

  1. The Emerging Prominence of the Cardiac Mast Cell as a Potent Mediator of Adverse Myocardial Remodeling

    PubMed Central

    Janicki, Joseph S.; Brower, Gregory L.; Levick, Scott P.

    2015-01-01

    Cardiac mast cells store and release a variety of biologically active mediators, several of which have been implicated in the activation of matrix metalloproteinases in the volume-overloaded heart, while others are involved in the fibrotic process in pressure-overloaded hearts. Increased numbers of mast cells have been reported in explanted human hearts with dilated cardiomyopathy and in animal models of experimentally induced hypertension, myocardial infarction, and chronic cardiac volume overload. Also, there is evolving evidence implicating the cardiac mast cell as having a major role in the adverse remodeling underlying these cardiovascular disorders. Thus, the cardiac mast cell is the focus of this chapter that begins with a historical background, followed by sections on methods for their isolation and characterization, endogenous secretagogues, phenotype, and ability of estrogen to alter their phenotype so as to provide cardioprotection. Finally the role of mast cells in myocardial remodeling secondary to a sustained cardiac volume overload, hypertension, and ischemic injury and future research directions are discussed. PMID:25388248

  2. Overexpression of VEGF-C attenuates chronic high salt intake-induced left ventricular maladaptive remodeling in spontaneously hypertensive rats.

    PubMed

    Yang, Guo-Hong; Zhou, Xin; Ji, Wen-Jie; Zeng, Shan; Dong, Yan; Tian, Lu; Bi, Ying; Guo, Zhao-Zeng; Gao, Fei; Chen, Hong; Jiang, Tie-Min; Li, Yu-Ming

    2014-02-15

    Recent studies have shown that the tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway-induced lymphangiogenesis provides a buffering mechanism for high salt (HS) intake-induced elevation of blood pressure (BP). Moreover, blocking of TonEBP/VEGF-C signaling by mononuclear phagocyte depletion can induce salt-sensitive hypertension in rats. We hypothesized that HS intake could have an impact on cardiac lymphangiogenesis, and regulation of VEGF-C bioactivity, which is largely through the main receptor for VEGFR-3, may modulate HS intake-induced left ventricular remodeling. We demonstrated upregulation of TonEBP, increased macrophage infiltration, and enhanced lymphangiogenesis in the left ventricles of spontaneously hypertensive rats (SHR) that were fed a HS diet (8.0% NaCl). Then, retrovirus vectors capable of overexpression (ΔNΔC/VEGF-C/Cys152Ser, used for overexpressing VEGF-C) and blocking (VEGFR-3-Rg, used for trapping of bioactive VEGF-C) of VEGF-C and control vector (pLPCX) were intravenously administered to SHR from week 9 of a 12-wk HS loading period. At the end of the HS challenge, overexpression of VEGF-C led to enhanced cardiac lymphangiogenesis, decreased myocardial fibrosis, and macrophage infiltration, preserved left ventricular functions, as well as decreased blood pressure level compared with the HS group and the control vector-treated HS group. In contrast, systemic blocking of VEGF-C was associated with elevation of blood pressure level and an exacerbation of hypertensive left ventricular remodeling, as indicated by increased fibrosis and macrophage infiltration, and diminished lymphangiogenesis. Hence, our findings highlight that VEGF-C/VEGFR-3 is a promising therapeutic target to attenuate hypertensive left ventricular remodeling induced by HS intake, presumably via blood pressure-dependent and -independent mechanisms. PMID:24337460

  3. RELATION OF LEFT VENTRICULAR MASS AND CONCENTRIC REMODELING TO EXTENT OF CORONARY ARTERY DISEASE BY COMPUTED TOMOGRAPHY IN PATIENTS WITHOUT LEFT VENTRICULAR HYPERTROPHY: ROMICAT STUDY

    PubMed Central

    Truong, Quynh A.; Toepker, Michael; Mahabadi, Amir A.; Bamberg, Fabian; Rogers, Ian S.; Blankstein, Ron; Brady, Thomas J.; Nagurney, John T.; Hoffmann, Udo

    2010-01-01

    Objective Cardiac computed tomography (CT) allows for simultaneous assessment of left ventricular mass (LVM) and coronary artery disease (CAD). We aimed to determine whether LVM, LVM index (LVMi), and the left ventricular (LV) geometric pattern of concentric remodeling are associated with the extent of CAD in patients without left ventricular hypertrophy (LVH). Methods In 348 patients from the ROMICAT trial, 64-slice CT was performed and LVM measured at end-diastole. We used 3 LVM indexation criteria to obtain 3 cohorts: LVM indexed to body surface area by echocardiography (n=337) and CT criteria (n=325), and by height2.7 (n=326). The cohorts were subdivided into concentric remodeling and normal geometry. Extent of coronary plaque was classified based on a 17-segment model, treated as a continuous variable, and stratified into 3 groups: 0 segments, 1–4 segments, >4 segments. Results Patients with >4 segments of coronary plaque had higher LVM (Δ12.8–15.1g) and LVMi (Δ4.0–5.5g/m2 and Δ2.2g/m2.7) than those without CAD (all p≤0.03). After multivariable adjustment, LVM and LVMi remained independent predictors of extent of coronary plaque, with 0.27–0.29 segments more plaque per 20 g increase of LVM (all p=0.02), 0.32–0.34 segments more plaque per 10 g/m2 increase of LVMi (both p=0.02), and 0.80 segments more plaque per 10 g/m2.7 increase of LVMi (p=0.008). Concentric remodeling patients had 1.1–1.3 segments more plaque than those with normal geometry (all p≤0.05). Patients with >4 segments of plaque had 2-fold increase odds (all p≤0.05) of having concentric remodeling as compared to those without CAD. Conclusion Increased LVM, LVMi, and concentric remodeling are associated with a greater degree of coronary plaque burden in patients without LVH. These findings could provide an indication to intensify medical therapy in patients with subclinical CAD and hypertension. PMID:19696685

  4. Residual stress impairs pump function after surgical ventricular remodeling: A finite element analysis

    PubMed Central

    Pantoja, Joe Luis; Zhang, Zhihong; Tartibi, Mehrzad; Sun, Kay; Macmillan, Warrick; Guccione, Julius M.; Ge, Liang; Ratcliffe, Mark B.

    2016-01-01

    Objectives Surgical ventricular restoration (Dor procedure) is generally thought to reduce left ventricular (LV) myofiber stress (FS) but to adversely affect pump function. However, the underlying mechanism is unclear. The goal of this study was to determine the effect of residual stress (RS) on LV FS and pump function after the Dor procedure. Methods Previously described finite element models of the LV based on MRI data obtained in five sheep 16 weeks after antero-apical myocardial infarction were used. Simulated Dacron patches that were elliptical and 25% of the infarct opening area were implanted using a virtual suture technique (VIRTUAL-DOR). In each case, diastole and systole were simulated and RS, FS, LV volumes, systolic and diastolic function, and pump (Starling) function were calculated. Results VIRTUAL-DOR was associated with significant RS that was tensile (2.89±1.31 kPa) in the remote myocardium and compressive (234.15±65.53 kPa) in the borderzone (BZ). VIRTUAL-DOR+RS (compared to VIRTUAL-DOR-NO-RS) was associated with further reduction in regional diastolic and systolic FS with the greatest change in the BZ (43.5-fold and 7.1-fold respectively, p<0.0001). VIRTUAL-DOR+RS was also associated with further reduction in systolic and diastolic volumes (7.9%, p=0.0606 and 10.6%, p=0.0630, respectively). The resultant effect was a further reduction in pump function after VIRTUAL-DOR+RS. Conclusion Residual stress that occurs after the Dor procedure is positive (tensile) in the remote myocardium and negative (compressive) in the BZ and associated with reductions in fiber stress and LV volumes. The resultant effect is a further reduction in LV pump (Starling) function. PMID:26341601

  5. Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

    PubMed Central

    Chacko, Paul; Jin, James; Tran, Tam; Prior, Thomas W.; He, Xin; Agarwal, Gunjan; Raman, Subha V.

    2016-01-01

    Patients with Friedreich ataxia typically die of cardiomyopathy, marked by myocardial fibrosis and abnormal left ventricular (LV) geometry. We measured procollagen I carboxyterminal propeptide (PICP), a serum biomarker of collagen production, and characterized genotypes, phenotypes, and outcomes in these patients. Twenty-nine patients with Friedreich ataxia (mean age, 34.2 ± 2.2 yr) and 29 healthy subjects (mean age, 32.5 ± 1.1 yr) underwent serum PICP measurements. Patients underwent cardiac magnetic resonance imaging and outcome evaluations at baseline and 12 months. Baseline PICP values were significantly higher in the patients than in the control group (1,048 ± 77 vs 614 ± 23 ng/mL; P <0.001); severity of genetic abnormality did not indicate severity of PICP elevation. Higher PICP levels corresponded to greater LV concentric remodeling only at baseline (r=0.37, P <0.05). Higher baseline PICP strongly indicated subsequent increases in LV end-diastolic volume (r=0.52, P=0.02). The PICP levels did not distinguish between 14 patients with evident myocardial fibrosis identified through positive late gadolinium enhancement and 15 who had no enhancement (1,067 ± 125 vs 1,030 ± 98 ng/mL; P=0.82). At 12 months, cardiac events had occurred in 3 of 14 fibrosis-positive and none of 15 fibrosis-negative patients (P=0.1); their baseline PICP levels were similar. We conclude that PICP, a serum marker of collagen synthesis, is elevated in Friedreich ataxia and indicates baseline abnormal LV geometry and subsequent dilation. Cardiac magnetic resonance and PICP warrant consideration as complementary biomarkers in therapeutic trials of Friedreich ataxia cardiomyopathy. PMID:27547137

  6. Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes.

    PubMed

    Mehta, Nishaki; Chacko, Paul; Jin, James; Tran, Tam; Prior, Thomas W; He, Xin; Agarwal, Gunjan; Raman, Subha V

    2016-08-01

    Patients with Friedreich ataxia typically die of cardiomyopathy, marked by myocardial fibrosis and abnormal left ventricular (LV) geometry. We measured procollagen I carboxyterminal propeptide (PICP), a serum biomarker of collagen production, and characterized genotypes, phenotypes, and outcomes in these patients. Twenty-nine patients with Friedreich ataxia (mean age, 34.2 ± 2.2 yr) and 29 healthy subjects (mean age, 32.5 ± 1.1 yr) underwent serum PICP measurements. Patients underwent cardiac magnetic resonance imaging and outcome evaluations at baseline and 12 months. Baseline PICP values were significantly higher in the patients than in the control group (1,048 ± 77 vs 614 ± 23 ng/mL; P <0.001); severity of genetic abnormality did not indicate severity of PICP elevation. Higher PICP levels corresponded to greater LV concentric remodeling only at baseline (r=0.37, P <0.05). Higher baseline PICP strongly indicated subsequent increases in LV end-diastolic volume (r=0.52, P=0.02). The PICP levels did not distinguish between 14 patients with evident myocardial fibrosis identified through positive late gadolinium enhancement and 15 who had no enhancement (1,067 ± 125 vs 1,030 ± 98 ng/mL; P=0.82). At 12 months, cardiac events had occurred in 3 of 14 fibrosis-positive and none of 15 fibrosis-negative patients (P=0.1); their baseline PICP levels were similar. We conclude that PICP, a serum marker of collagen synthesis, is elevated in Friedreich ataxia and indicates baseline abnormal LV geometry and subsequent dilation. Cardiac magnetic resonance and PICP warrant consideration as complementary biomarkers in therapeutic trials of Friedreich ataxia cardiomyopathy. PMID:27547137

  7. Reduced fractional shortening of right ventricular outflow tract is associated with adverse outcomes in patients with left ventricular dysfunction

    PubMed Central

    2013-01-01

    Background Recent studies suggest the significance of right ventricular (RV) function in the outcome in patients with left ventricular dysfunction (LVSD); however, global assessment of RV remains to be determined by echocardiogram because of its complex geometry. This study aimed to validate RV outflow tract fractional shortening (RVOT-FS) in the evaluation of RV function and its prognostic value in patients with LVSD. Methods This study included eighty-one patients (62 ± 17 years, mean ± SD, male 79%) with reduced LV ejection fraction (LVEF) (≤40%). Two-dimensional echocardiogram of the parasternal short axis view was obtained at the level of the aortic root, and RVOT-FS was calculated as the ratio of end-diastole minus end-systole dimension to end-diastole dimension. Results RVOT-FS ranged from 0.04 to 0.8 (0.3 ± 0.2, mean ± SD), and correlated with LVEF (r = 0.33, p = 0.0028), RV fractional area change (r = 0.37, p = 0.0008) and brain natriuretic peptide level (r = -0.38, p = 0.0005). In Cox multivariate regression analysis, RVOT-FS [hazard ratio (HR) 0.028, 95% confidence interval (CI): 0.002-0.397]; p = 0.008] and New York Heart Association functional class III-IV [HR 2.233, 95% CI: 1.048-4.761]; p = 0.037] were independent factors to predict the events. During a median follow-up period of 319 days (1 to 1862 days), patients with RVOT-FS ≥ 0.2 showed a higher event-free rate than those < 0.2 by Kaplan-Meier analysis (log-rank test, p = 0.0016). Conclusions Our data suggest that RVOT-FS is a simple parameter reflecting the severity of both ventricular function in patients with LVSD. In addition, RVOT-FS might be useful to predict adverse outcomes in such a patient population. PMID:23731725

  8. Simvastatin ameliorates ventricular remodeling via the TGF‑β1 signaling pathway in rats following myocardial infarction.

    PubMed

    Xiao, Xiangbin; Chang, Guanglei; Liu, Jian; Sun, Guangyun; Liu, Li; Qin, Shu; Zhang, Dongying

    2016-06-01

    Statins are widely used in patients with cardiovascular diseases. A considerable number of previous studies revealed that the intracellular signaling of transforming growth factor (TGF)‑β1 mediated the development of cardiomyocyte hypertrophy and interstitial fibrosis. However, whether statins can ameliorate ventricular remodeling in post‑myocardial infarction via the TGF‑β1 signaling pathway remains to be rigorously tested. The left anterior descending artery was ligated to induce a rat model of myocardial infarction. The rat model of myocardial infarction was treated with simvastatin through gastric gavage (10, 20 or 40 mg kg‑1·d‑1). All rats were sacrificed on day 28 after the myocardial infarction operation. The results revealed that simvastatin significantly improved the hemodynamic indexes, left ventricular mass index, the myocardial tissue structure, the cardiomyocyte cross‑sectional area and the collagen volume fraction, and also showed that the levels of TGF‑β1, TGF‑activated kinase (TAK)1 and drosophila mothers against decapentaplegic (Smad)3 were significantly reduced following treatment with simvastatin, while the levels of Smad7 in the simvastatin treatment groups were markedly increased. The results of the present study suggested that statins ameliorated ventricular remodeling in post‑myocardial infarction rats via the TGF‑β1 signaling pathway, which provided a novel explanation for the pleiotropic effects of statins that benefit the cardiovascular system. PMID:27121011

  9. Simvastatin ameliorates ventricular remodeling via the TGF-β1 signaling pathway in rats following myocardial infarction

    PubMed Central

    XIAO, XIANGBIN; CHANG, GUANGLEI; LIU, JIAN; SUN, GUANGYUN; LIU, LI; QIN, SHU; ZHANG, DONGYING

    2016-01-01

    Statins are widely used in patients with cardiovascular diseases. A considerable number of previous studies revealed that the intracellular signaling of transforming growth factor (TGF)-β1 mediated the development of cardiomyocyte hypertrophy and interstitial fibrosis. However, whether statins can ameliorate ventricular remodeling in post-myocardial infarction via the TGF-β1 signaling pathway remains to be rigorously tested. The left anterior descending artery was ligated to induce a rat model of myocardial infarction. The rat model of myocardial infarction was treated with simvastatin through gastric gavage (10, 20 or 40 mg kg−1·d−1). All rats were sacrificed on day 28 after the myocardial infarction operation. The results revealed that simvastatin significantly improved the hemodynamic indexes, left ventricular mass index, the myocardial tissue structure, the cardiomyocyte cross-sectional area and the collagen volume fraction, and also showed that the levels of TGF-β1, TGF-activated kinase (TAK)1 and drosophila mothers against decapentaplegic (Smad)3 were significantly reduced following treatment with simvastatin, while the levels of Smad7 in the simvastatin treatment groups were markedly increased. The results of the present study suggested that statins ameliorated ventricular remodeling in post-myocardial infarction rats via the TGF-β1 signaling pathway, which provided a novel explanation for the pleiotropic effects of statins that benefit the cardiovascular system. PMID:27121011

  10. Natakalim improves post-infarction left ventricular remodeling by restoring the coordinated balance between endothelial function and cardiac hypertrophy.

    PubMed

    Zhou, Hong-Min; Zhong, Ming-Li; Zhang, Yan-Fang; Cui, Wen-Yu; Long, Chao-Liang; Wang, Hai

    2014-11-01

    Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (K(ATP)) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel K(ATP) channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evidence of left ventricular remodeling and congestive heart failure were observed in the rats with myocardial infarction. Treatment with natakalim at daily oral doses of 1, 3 or 9 mg/kg/day for 8 weeks prevented these changes. Natakalim also prevented the progression to cardiac failure, which was demonstrated by the increase in right ventricular weight/body weight (RVW/BW) and relative lung weight, signs of cardiac dysfunction, as well as the overexpression of atrial and brain natriuretic peptide mRNAs. Our results also demonstrated that natakalim enhanced the downregulation of endothelium-derived nitric oxide, attenuated the upregulation of inducible nitric oxide synthase-derived nitric oxide (NO), inhibited the upregulated endothelin system and corrected the imbalance between prostacyclin and thromboxane A(2). Overall, our findings suggest that natakalim prevents post-infarction hypertrophy and cardiac failure by restoring the coordinated balance between endothelial function and cardiac hypertrophy. PMID:25215478

  11. Albuminuria is Independently Associated with Cardiac Remodeling, Abnormal Right and Left Ventricular Function, and Worse Outcomes in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Katz, Daniel H.; Burns, Jacob A.; Aguilar, Frank G.; Beussink, Lauren; Shah, Sanjiv J.

    2014-01-01

    Objectives To determine the relationship between albuminuria and cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). Background Albuminuria, a marker of endothelial dysfunction, has been associated with adverse cardiovascular outcomes in HFpEF. However, the relationship between albuminuria and cardiac structure/function in HFpEF has not been well studied. Methods We measured urinary albumin-to-creatinine ratio (UACR) and performed comprehensive echocardiography, including tissue Doppler imaging and right ventricular (RV) evaluation, in a prospective study of 144 patients with HFpEF. Multivariable-adjusted linear regression was used to determine the association between UACR and echocardiographic parameters. Cox proportional hazards analyses were used to determine the association between UACR and outcomes. Results The mean age was 66±11 years, 62% were female, and 42% were African-American. Higher UACR was associated with greater left ventricular (LV) mass, lower preload-recruitable stroke work, and lower global longitudinal strain. Higher UACR was also significantly associated with RV remodeling (for each doubling of UACR, RV wall thickness was 0.9 mm higher [95% confidence interval (CI) 0.05–0.14 mm; P=0.001, adjusted P=0.01]) and worse RV systolic function (for each doubling of UACR, RV fractional area change was 0.56% lower [95% CI 0.14–0.98%; P=0.01, adjusted P=0.03]. The association between UACR and RV parameters persisted after excluding patients with macroalbuminuria (UACR > 300 mg/g). Increased UACR was also independently associated with worse outcomes. Conclusions In HFpEF, increased UACR is a prognostic marker and is associated with increased RV and LV remodeling, and longitudinal systolic dysfunction. PMID:25282032

  12. Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation

    PubMed Central

    Ainslie, Philip N.; Hughes, Michael G.; Stöhr, Eric J.; Cotter, James D.; Nio, Amanda Q. X.; Shave, Rob

    2014-01-01

    Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. PMID:24876358

  13. Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation.

    PubMed

    Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G; Stöhr, Eric J; Cotter, James D; Nio, Amanda Q X; Shave, Rob

    2014-08-01

    Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. PMID:24876358

  14. Asiatic acid inhibits left ventricular remodeling and improves cardiac function in a rat model of myocardial infarction

    PubMed Central

    HUO, LIANYING; SHI, WENBING; CHONG, LING; WANG, JINLONG; ZHANG, KAI; LI, YUFENG

    2016-01-01

    Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI. PMID:26889217

  15. Comparison of Macitentan and Bosentan on Right Ventricular Remodeling in a Rat Model of Non-vasoreactive Pulmonary Hypertension

    PubMed Central

    Landskroner, Kyle; Bauer, Yasmina; Vercauteren, Magali; Rey, Markus; Renault, Berengère; Studer, Rolf; Vezzali, Enrico; Freti, Diego; Hadana, Hakim; Schläpfer, Manuela; Cattaneo, Christophe; Bortolamiol, Céline; Weber, Edgar; Whitby, Brian R.; Delahaye, Stéphane; Wanner, Daniel; Steiner, Pauline; Nayler, Oliver; Hess, Patrick; Clozel, Martine

    2015-01-01

    Aims: We compared the efficacy of macitentan, a novel dual endothelin A/endothelin B receptor antagonist, with that of another dual endothelin receptor antagonist, bosentan, in a rat model of non-vasoreactive pulmonary hypertension (PH) with particular emphasis on right ventricular (RV) remodeling. Methods and Results: Unlike monocrotaline or hypoxic/sugen rats, bleomycin-treated rats presented a non-vasoreactive PH characterized by the absence of pulmonary dilatation to adenosine. We therefore chose the bleomycin rat model to compare the effects of the maximally effective doses of macitentan and bosentan on pulmonary vascular and RV remodeling. Macitentan (100 mg·kg−1·d−1), but not bosentan (300 mg·kg−1·d−1), significantly prevented pulmonary vascular remodeling, RV hypertrophy, and cardiomyocyte diameter increase. Cardiac protection by macitentan was associated with a significant attenuation of genes related to cell hypertrophy and extracellular matrix remodeling. Microautoradiography and high performance liquid chromatography analysis showed greater distribution of macitentan than bosentan in the RV and pulmonary tissue. Conclusions: Macitentan was more efficacious than bosentan in preventing the development of pulmonary and RV hypertrophies in a model of non-vasoreactive PH. Greater ability to distribute into the tissue could contribute to the greater structural improvement by macitentan compared with bosentan. PMID:26230396

  16. Risk stratification for major adverse cardiac events and ventricular tachyarrhythmias by cardiac MRI in patients with cardiac sarcoidosis

    PubMed Central

    Yasuda, Masakazu; Iwanaga, Yoshitaka; Kato, Takao; Izumi, Toshiaki; Inuzuka, Yasutaka; Nakamura, Takashi; Miyaji, Yuki; Kawamura, Takayuki; Ikeguchi, Shigeru; Inoko, Moriaki; Kurita, Takashi; Miyazaki, Shunichi

    2016-01-01

    Background The presence of myocardial fibrosis by cardiac MRI has prognostic value in cardiac sarcoidosis, and localisation may be equally relevant to clinical outcomes. Objective We aimed to analyse cardiac damage and function in detail and explore the relationship with clinical outcomes in patients with cardiac sarcoidosis using cardiac MRI. Methods We included 81 consecutive patients with cardiac sarcoidosis undergoing cardiac MR. Left ventricular mass and fibrosis mass were calculated, and localisation was analysed using a 17-segment model. Participants underwent follow-up through 2015, and the development of major adverse cardiac events including ventricular tachyarrhythmias was recorded. Results Increased left ventricular fibrosis mass was associated with increased prevalence of ventricular tachyarrhythmias (p<0.001). When localisation was defined as the sum of late gadolinium enhancement in the left ventricular basal anterior and basal anteroseptal areas, or the right ventricular area, it was associated with ventricular tachyarrhythmias (p<0.001). Kaplan-Meier analysis during a median follow-up of 22.1 months showed that both the mass and localisation groupings for fibrosis were significantly associated with major adverse cardiac events or ventricular tachyarrhythmias and that when combined, the risk stratification was better than for each variable alone (p<0.001, respectively). By Cox-proportional hazard risk analysis, the localisation grouping was an independent predictor for the both. Conclusions In patients with cardiac sarcoidosis, both fibrosis mass and its localisation to the basal anterior/anteroseptal left ventricle, or right ventricle was associated with the development of major adverse cardiac events or ventricular tachyarrhythmias. Cardiac MR with late gadolinium enhancement may be useful for improving risk stratification in patients with cardiac sarcoidosis. PMID:27547432

  17. Impact of Atrial Fibrillation Ablation on Left Ventricular Filling Pressure and Left Atrial Remodeling

    PubMed Central

    dos Santos, Simone Nascimento; Henz, Benhur Davi; Zanatta, André Rodrigues; Barreto, José Roberto; Loureiro, Kelly Bianca; Novakoski, Clarissa; dos Santos, Marcus Vinícius Nascimento; Giuseppin, Fabio F.; Oliveira, Edna Maria; Leite, Luiz Roberto

    2014-01-01

    Background Left ventricular (LV) diastolic dysfunction is associated with new-onset atrial fibrillation (AF), and the estimation of elevated LV filling pressures by E/e' ratio is related to worse outcomes in patients with AF. However, it is unknown if restoring sinus rhythm reverses this process. Objective To evaluate the impact of AF ablation on estimated LV filling pressure. Methods A total of 141 patients underwent radiofrequency (RF) ablation to treat drug-refractory AF. Transthoracic echocardiography was performed 30 days before and 12 months after ablation. LV functional parameters, left atrial volume index (LAVind), and transmitral pulsed and mitral annulus tissue Doppler (e' and E/e') were assessed. Paroxysmal AF was present in 18 patients, persistent AF was present in 102 patients, and long-standing persistent AF in 21 patients. Follow-up included electrocardiographic examination and 24-h Holter monitoring at 3, 6, and 12 months after ablation. Results One hundred seventeen patients (82.9%) were free of AF during the follow-up (average, 18 ± 5 months). LAVind reduced in the successful group (30.2 mL/m2 ± 10.6 mL/m2 to 22.6 mL/m2 ± 1.1 mL/m2, p < 0.001) compared to the non-successful group (37.7 mL/m2 ± 14.3 mL/m2 to 37.5 mL/m2 ± 14.5 mL/m2, p = ns). Improvement of LV filling pressure assessed by a reduction in the E/e' ratio was observed only after successful ablation (11.5 ± 4.5 vs. 7.1 ± 3.7, p < 0.001) but not in patients with recurrent AF (12.7 ± 4.4 vs. 12 ± 3.3, p = ns). The success rate was lower in the long-standing persistent AF patient group (57% vs. 87%, p = 0.001). Conclusion Successful AF ablation is associated with LA reverse remodeling and an improvement in LV filling pressure. PMID:25590928

  18. Effects of buyang huanwu decoction on ventricular remodeling and differential protein profile in a rat model of myocardial infarction.

    PubMed

    Zhou, Ying Chun; Liu, Bin; Li, Ying Jia; Jing, Lin Lin; Wen, Ge; Tang, Jing; Xu, Xin; Lv, Zhi Ping; Sun, Xue Gang

    2012-01-01

    Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from "Correction on Errors in Medical Classics" in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18 g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF. PMID:23049607

  19. Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling

    PubMed Central

    Lehmann, Lorenz H.; Rostosky, Julia S.; Buss, Sebastian J.; Kreusser, Michael M.; Krebs, Jutta; Mier, Walter; Enseleit, Frank; Spiger, Katharina; Hardt, Stefan E.; Wieland, Thomas; Haass, Markus; Lüscher, Thomas F.; Schneider, Michael D.; Parlato, Rosanna; Gröne, Hermann-Josef; Haberkorn, Uwe; Yanagisawa, Masashi; Katus, Hugo A.; Backs, Johannes

    2014-01-01

    In preclinical studies, endothelin receptor A (ETA) antagonists (ETAi) attenuated the progression of heart failure (HF). However, clinical HF trials failed to demonstrate beneficial effects of ETAi. These conflicting data may be explained by the possibility that established HF drugs such as adrenergic receptor blockers interfered with the mechanism of ETAi action in clinical trials. Here we report that mice lacking ETA only in sympathetic neurons (SN-KO) showed less adverse structural remodeling and cardiac dysfunction in response to pathological pressure overload induced by transverse aortic constriction (TAC). In contrast, mice lacking ETA only in cardiomyocytes (CM-KO) were not protected. TAC led to a disturbed sympathetic nerve function as measured by cardiac norepinephrine (NE) tissue levels and [124I]-metaiodobenzylguanidine-PET, which was prevented in SN-KO. In a rat model of HF, ETAi improved cardiac and sympathetic nerve function. In cocultures of cardiomyocytes (CMs) and sympathetic neurons (SNs), endothelin-1 (ET1) led to a massive NE release and exaggerated CM hypertrophy compared with CM monocultures. ETA-deficient CMs gained a hypertrophic response through wild-type SNs, but ETA-deficient SNs failed to mediate exaggerated CM hypertrophy. Furthermore, ET1 mediated its effects indirectly via NE in CM-SN cocultures through adrenergic receptors and histone deacetylases, resulting in activation of the prohypertrophic transcription factor myocyte enhancer factor 2. In conclusion, sympathetic ETA amplifies ET1 effects on CMs through adrenergic signaling pathways. Thus, antiadrenergic therapies may blunt potentially beneficial effects of ETAi. Taken together, this may indicate that patients with β blocker intolerance or disturbed sympathetic nerve function could be evaluated for a potential benefit from ETAi. PMID:25197047

  20. Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

    PubMed Central

    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

  1. Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation.

    PubMed

    Linz, Dominik; Mahfoud, Felix; Schotten, Ulrich; Ukena, Christian; Hohl, Mathias; Neuberger, Hans-Ruprecht; Wirth, Klaus; Böhm, Michael

    2013-01-01

    Renal denervation (RDN) reduces renal efferent and afferent sympathetic activity thereby lowering blood pressure in resistant hypertension. The effect of modulation of the autonomic nervous system by RDN on atrial electrophysiology and ventricular rate control during atrial fibrillation (AF) is unknown. Here we report a reduction of ventricular heart rate in a patient with permanent AF undergoing RDN. Subsequently, we investigated the effect of RDN on AF-induced shortening of atrial effective refractory period, AF inducibility, and ventricular rate control during AF maintained by rapid atrial pacing in 12 pigs undergoing RDN (n=7) or sham procedure (n=5). During sinus rhythm, RDN reduced heart rate (RR-interval, 708±12 versus 577±19 ms; P=0.0021) and increased atrioventricular node conduction time (PQ-interval, 112±12 versus 88±9 ms; P=0.0001). Atrial tachypacing for 30 minutes increased AF inducibility and decreased AF cycle length. This was not influenced by RDN. RDN reduced ventricular rate during AF episodes by ≈24% (119±9 versus 158±19 bpm; P=0.0001). AF episodes were shorter after RDN compared with sham (12±3 versus 34±4 s; P=0.0091), but atrial effective refractory period was not modified by RDN. RDN reduced heart rate and reduced atrioventricular node conduction time during sinus rhythm and provided rate control during AF. AF-induced atrial electrical remodeling, AF inducibility, and AF cycle length were not modified, but duration of AF episodes was shorter after RDN. Modulation of the autonomic nervous system by RDN might provide rate control and reduce susceptibility to AF. Whether RDN may provide rate control in a larger number of patients with AF deserves further clinical studies. PMID:23150501

  2. Compatibility of Astragalus and Salvia extract inhibits myocardial fibrosis and ventricular remodeling by regulation of protein kinase D1 protein

    PubMed Central

    Mao, Bingyu; Nuan, Liu; Yang, Lei; Zeng, Xiaotao

    2015-01-01

    Aims: This study is to determine the effect of astragalus and salvia extract on the alteration of myocardium in a rat model of myocardial infarction. Methods: A total of 40 male Sprague-Dawley rats were randomly divided into the sham-operated group, the control group, the Astragalus group, the Salvia group, and the compatibility of Astragalus and Salvia and group. The cardiac functions were determined at 8 weeks after treatment. Hematoxylin-eosin staining was performed to observe the morphology and arrangement of cardiomyocytes. Masson’s trichrome staining was performed to investigate the distribution of myocardial interstitial collagen. Immunohistochemical staining was performed to determine the expression ofprotein kinase D1 in myocardial tissues. Results: In the sham-operated group, the Astragalus group, the Salvia group, and the compatibility of Astragalus and Salvia group, the left ventricular systolic pressure and the maximum rate of left ventricular pressure were significantly increased while the left ventricular end diastolic pressure were significantly decreased when compared with those in the control group (P < 0.05). Normal morphology and arrangement of cardiomyocytes were maintained in the compatibility of Astragalus and Salvia group. Contents of collagen fibers in myocardial tissues were decreased in the compatibility of Astragalus and Salvia group (P < 0.05). Expression levels of protein kinase D1 were significantly decreased in cardiomyocytes of the compatibility of Astragalus and Salvia group. Conclusions: Compatibility of Astragalus and Salvia extract may inhibit myocardial fibrosis and ventricular remodeling by regulation of protein kinase D1 protein in a rat model of myocardial infarction. PMID:26064267

  3. Internal associations and dynamic expression of c-kit and nanog genes in ventricular remodelling induced by adriamycin

    PubMed Central

    Liu, Zhen; Li, Shuo; Liu, Lingling; Guo, Zhikun; Wang, Pengfei

    2016-01-01

    The present study aimed to investigate the dynamic expression of the c-kit and nanog genes in rats with left ventricular remodelling induced by adriamycin (ADR), and explore its internal association and mechanism of action. Sprague-Dawley male rats were randomly divided into a normal control group and a heart failure model group. Heart failure was induced by a single intraperitoneal injection of ADR (4 mg/kg) weekly for six weeks. The normal control group was given the same amount of saline. At the eighth week, rat cardiac function was examined to demonstrate the formation of heart failure. The rat hearts were harvested frozen and sectioned, and the expression levels of the nanog and c-kit genes in the myocardial tissue samples were detected using immunohistochemistry, immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). Hematoxylin and eosin staining demonstrated various pathological changes in the myocardial cells in the heart failure model group, whereas myocardial infarction was not observed in the normal control group. Immunohistochemistry and immunofluorescence demonstrated that nanog-positive cells were predominantly expressed in the vascular endothelium, with a few myocardial cells and stem cells in normal myocardium. The expression levels of c-kit and nanog in the myocardium of the rats with heart failure decreased significantly. c-kit-positive cells clustered together in the epicardium and its vicinity, and c-kit expression significantly decreased in the myocardium of rats with heart failure, as compared with normal rats. In both groups, some cells co-expressed both the c-kit and nanog genes. The RT-PCR results demonstrated that the expression levels of the two genes in the heart failure model group were significantly lower compared with those in the normal control group (P<0.05). In conclusion, the c-kit- and nanog-positive stem cells decreased in the myocardium of the rats with left ventricular remodelling induced by ADR

  4. Nitric oxide mediates cardiac protection of tissue kallikrein by reducing inflammation and ventricular remodeling after myocardial ischemia/reperfusion

    PubMed Central

    Yin, Hang; Chao, Lee; Chao, Julie

    2008-01-01

    We assessed the role of nitric oxide (NO) and the kinin B2 receptor in mediating tissue kallikrein’s actions in intramyocardial inflammation and cardiac remodeling after ischemia/reperfusion (I/R) injury. Adenovirus carrying the human tissue kallikrein gene was delivered locally into rat hearts 4 days prior to 30-minute ischemia followed by 24- hour or 7-day reperfusion with or without administration of icatibant, a kinin B2 receptor antagonist, or N(ω)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Kallikrein gene delivery improved cardiac contractility and diastolic function, reduced infarct size at 1 day after I/R without affecting mean arterial pressure. Kallikrein treatment reduced macrophage/monocyte and neutrophil accumulation in the infarcted myocardium in association with reduced intercellular adhesion molecule-1 levels. Kallikrein increased cardiac endothelial nitric oxide synthase phosphorylation and NO levels and decreased superoxide formation, TGF-β1 levels and Smad2 phosphorylation. Furthermore, kallikrein reduced I/R-induced JNK, p38MAPK, IκB-α phosphorylation and nuclear NF-κB activation. In addition, kallikrein improved cardiac performance, reduced infarct size and prevented ventricular wall thinning at 7 days after I/R. The effects of kallikrein on cardiac function, inflammation and signaling mediators were all blocked by icatibant and L-NAME. These results indicate that tissue kallikrein through kinin B2 receptor and NO formation improves cardiac function, prevents inflammation and limits left ventricular remodeling after myocardial I/R by suppression of oxidative stress, TGF-β1/Smad2 and JNK/p38MAPK signaling pathways and NF-κB activation. PMID:18068196

  5. Stem cell mechanisms during left ventricular remodeling post-myocardial infarction: Repair and regeneration

    PubMed Central

    Zamilpa, Rogelio; Navarro, Mary M; Flores, Iris; Griffey, Sy

    2014-01-01

    Post-myocardial infarction (MI), the left ventricle (LV) undergoes a series of events collectively referred to as remodeling. As a result, damaged myocardium is replaced with fibrotic tissue consequently leading to contractile dysfunction and ultimately heart failure. LV remodeling post-MI includes inflammatory, fibrotic, and neovascularization responses that involve regulated cell recruitment and function. Stem cells (SCs) have been transplanted post-MI for treatment of LV remodeling and shown to improve LV function by reduction in scar tissue formation in humans and animal models of MI. The promising results obtained from the application of SCs post-MI have sparked a massive effort to identify the optimal SC for regeneration of cardiomyocytes and the paradigm for clinical applications. Although SC transplantations are generally associated with new tissue formation, SCs also secrete cytokines, chemokines and growth factors that robustly regulate cell behavior in a paracrine fashion during the remodeling process. In this review, the different types of SCs used for cardiomyogenesis, markers of differentiation, paracrine factor secretion, and strategies for cell recruitment and delivery are addressed. PMID:25068021

  6. Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function-A Magnetic Resonance Image Study

    PubMed Central

    Lin, Lian-Yu; Su, Mao-Yuan M.; Pham, Van-Truong; Tran, Thi-Thao; Wang, Yung-Hung; Tseng, Wen-Yih I.; Lo, Men-Tzung; Lin, Jiunn-Lee

    2016-01-01

    Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function. PMID:26876005

  7. Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function--A Magnetic Resonance Image Study.

    PubMed

    Lin, Lian-Yu; Su, Mao-Yuan M; Pham, Van-Truong; Tran, Thi-Thao; Wang, Yung-Hung; Tseng, Wen-Yih I; Lo, Men-Tzung; Lin, Jiunn-Lee

    2016-01-01

    Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function. PMID:26876005

  8. Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling.

    PubMed

    Nisbet, Ashley M; Camelliti, Patrizia; Walker, Nicola L; Burton, Francis L; Cobbe, Stuart M; Kohl, Peter; Smith, Godfrey L

    2016-05-01

    Conduction abnormalities are frequently associated with cardiac disease, though the mechanisms underlying the commonly associated increases in PQ interval are not known. This study uses a chronic left ventricular (LV) apex myocardial infarction (MI) model in the rabbit to create significant left ventricular dysfunction (LVD) 8weeks post-MI. In vivo studies established that the PQ interval increases by approximately 7ms (10%) with no significant change in average heart rate. Optical mapping of isolated Langendorff perfused rabbit hearts recapitulated this result: time to earliest activation of the LV was increased by 14ms (16%) in the LVD group. Intra-atrial and LV transmural conduction times were not altered in the LVD group. Isolated AVN preparations from the LVD group demonstrated a significantly longer conduction time (by approximately 20ms) between atrial and His electrograms than sham controls across a range of pacing cycle lengths. This difference was accompanied by increased effective refractory period and Wenckebach cycle length, suggesting significantly altered AVN electrophysiology post-MI. The AVN origin of abnormality was further highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN preparations revealed increased fibrosis and gap junction protein (connexin43 and 40) remodelling in the AVN of LVD animals compared to sham. A significant increase in myocyte-non-myocyte connexin co-localization was also observed after LVD. These changes may increase the electrotonic load experienced by AVN muscle cells and contribute to slowed conduction velocity within the AVN. PMID:27021518

  9. Intracoronary Delivery of Self-Assembling Heart-Derived Microtissues (“Cardiospheres”) for Prevention of Adverse Remodeling in a Pig Model of Convalescent Myocardial Infarction

    PubMed Central

    Gallet, Romain; Tseliou, Eleni; Dawkins, James; Middleton, Ryan; Valle, Jackelyn; Angert, David; Reich, Heidi; Luthringer, Daniel; Kreke, Michelle; Smith, Rachel; Marbán, Linda; Marbán, Eduardo

    2015-01-01

    Background Preclinical studies in rodents and pigs indicate that the self-assembling microtissues known as cardiospheres (CSp) may be more effective than dispersed CSp-derived cells (CDCs). However, the more desirable intracoronary (IC) route has been assumed to be unsafe for CSp delivery: CSp are large (30-150 μm), raising concerns about likely micro-embolization. We questioned these negative assumptions by evaluating the safety and efficacy of optimized IC delivery of CSp in a porcine model of convalescent MI. Methods and Results First, we standardized the size of CSp by modifying culture conditions. Then, dosage was determined by infusing escalating doses of CSp in the LAD of naïve pigs, looking for acute adverse effects. Finally in a randomized efficacy study, 14 mini-pigs received allogeneic CSp (1.3×106) or vehicle one month following MI. Animals underwent MRI before infusion and 1 month later to assess left ventricular (LV) ejection fraction (EF), scar mass and viable mass. In the dosing study, we did not observe any evidence of micro-embolization after CSp infusion. In the post-MI study, CSp preserved LV function, reduced scar mass and increased viable mass whereas placebo did not. Moreover, CSp decreased collagen content, and increased vessel densities and myocardial perfusion. Importantly, IC CSp decreased LV end diastolic pressure and increased cardiac output. Conclusions Intracoronary delivery of CSp is safe. Intracoronary CSp are also remarkably effective in decreasing scar, halting adverse remodeling, increasing myocardial perfusion and improving hemodynamic status post-MI in pigs. Thus, CSp may be viable therapeutic candidates for IC infusion in selected myocardial disorders. PMID:25953823

  10. Hypertension: An Unstudied Potential Risk Factor for Adverse Outcomes during Continuous Flow Ventricular Assist Device Support

    PubMed Central

    Wasson, Lauren T.; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P.; Demmer, Ryan T.; Colombo, Paolo C.

    2014-01-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device-implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device-implantation HTN as a potential predictor of adverse CF-LVAD outcomes. Hypertension among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard non-invasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-deflation cuff system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may i) consider potential mechanisms relating HTN to poor outcomes, ii) realize that HTN management is a stated goal despite scarce evidence, and iii) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward. PMID:25283767

  11. Hypertension: an unstudied potential risk factor for adverse outcomes during continuous flow ventricular assist device support.

    PubMed

    Wasson, Lauren T; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P; Demmer, Ryan T; Colombo, Paolo C

    2015-05-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device implantation HTN as a potential predictor of adverse CF-LVAD outcomes. HTN among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard noninvasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-cuff deflation system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may (1) consider potential mechanisms relating HTN to poor outcomes, (2) realize that HTN management is a stated goal despite scarce evidence, and (3) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward. PMID:25283767

  12. Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury.

    PubMed

    Kapopara, P R; von Felden, J; Soehnlein, O; Wang, Y; Napp, L C; Sonnenschein, K; Wollert, K C; Schieffer, B; Gaestel, M; Bauersachs, J; Bavendiek, U

    2014-12-01

    Maladaptive remodelling of the arterial wall after mechanical injury (e. g. angioplasty) is characterised by inflammation, neointima formation and media hypertrophy, resulting in narrowing of the affected artery. Moreover, mechanical injury of the arterial wall causes loss of the vessel protecting endothelial cell monolayer. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, regulates inflammation, cell migration and proliferation, essential processes for vascular remodelling and re-endothelialisation. Therefore, we investigated the role of MK2 in remodelling and re-endothelialisation after arterial injury in genetically modified mice in vivo. Hypercholesterolaemic low-density-lipoprotein-receptor-deficient mice (ldlr-/-) were subjected to wire injury of the common carotid artery. MK2-deficiency (ldlr-/-/mk2-/-) nearly completely prevented neointima formation, media hypertrophy, and lumen loss after injury. This was accompanied by reduced proliferation and migration of MK2-deficient smooth muscle cells. In addition, MK2-deficiency severely reduced monocyte adhesion to the arterial wall (day 3 after injury, intravital microscopy), which may be attributed to reduced expression of the chemokine ligands CCL2 and CCL5. In line, MK2-deficiency significantly reduced the content of monocytes, neutrophiles and lymphocytes of the arterial wall (day 7 after injury, flow cytometry). In conclusion, in a model of endothelial injury (electric injury), MK2-deficiency strongly increased proliferation of endothelial cells and improved re-endothelialisation of the arterial wall after injury. Deficiency of MK2 prevents adverse remodelling and promotes endothelial healing of the arterial wall after injury, suggesting that MK2-inhibition is a very attractive intervention to prevent restenosis after percutaneous therapeutic angioplasty. PMID:25120198

  13. Altered Diastolic Flow Patterns and Kinetic Energy in Subtle Left Ventricular Remodeling and Dysfunction Detected by 4D Flow MRI

    PubMed Central

    Fredriksson, Alexandru; Eriksson, Jonatan; Dyverfeldt, Petter; Ebbers, Tino; Bolger, Ann F.; Engvall, Jan; Carlhäll, Carl-Johan

    2016-01-01

    Aims 4D flow magnetic resonance imaging (MRI) allows quantitative assessment of left ventricular (LV) function according to characteristics of the dynamic flow in the chamber. Marked abnormalities in flow components’ volume and kinetic energy (KE) have previously been demonstrated in moderately dilated and depressed LV’s compared to healthy subjects. We hypothesized that these 4D flow-based measures would detect even subtle LV dysfunction and remodeling. Methods and Results We acquired 4D flow and morphological MRI data from 26 patients with chronic ischemic heart disease with New York Heart Association (NYHA) class I and II and with no to mild LV systolic dysfunction and remodeling, and from 10 healthy controls. A previously validated method was used to separate the LV end-diastolic volume (LVEDV) into functional components: direct flow, which passes directly to ejection, and non-ejecting flow, which remains in the LV for at least 1 cycle. The direct flow and non-ejecting flow proportions of end-diastolic volume and KE were assessed. The proportions of direct flow volume and KE fell with increasing LVEDV-index (LVEDVI) and LVESV-index (LVESVI) (direct flow volume r = -0.64 and r = -0.74, both P<0.001; direct flow KE r = -0.48, P = 0.013, and r = -0.56, P = 0.003). The proportions of non-ejecting flow volume and KE rose with increasing LVEDVI and LVESVI (non-ejecting flow volume: r = 0.67 and r = 0.76, both P<0.001; non-ejecting flow KE: r = 0.53, P = 0.005 and r = 0.52, P = 0.006). The proportion of direct flow volume correlated moderately to LVEF (r = 0.68, P < 0.001) and was higher in a sub-group of patients with LVEDVI >74 ml/m2 compared to patients with LVEDVI <74 ml/m2 and controls (both P<0.05). Conclusion Direct flow volume and KE proportions diminish with increased LV volumes, while non-ejecting flow proportions increase. A decrease in direct flow volume and KE at end-diastole proposes that alterations in these novel 4D flow-specific markers may detect

  14. Effects of quinapril on myocardial function, ventricular remodeling and cardiac cytokine expression in congestive heart failure in the rat.

    PubMed

    We, Ge Cheng; Siroi, Martin G; Qu, Rong; Liu, Peter; Roulea, Jean L

    2002-01-01

    Inflammatory cytokines have been shown to be activated in congestive heart failure (CHF). This activation is likely the result of the convergence of a number of factors, several of which could be attenuated with the use of an Angiotensin converting enzyme (ACE) inhibitor. In order to assess this, rats had a myocardial infarction (MI) created by coronary artery ligation and were followed for 28 days without treatment to permit the development of CHF. At that time, the ACE inhibitor quinapril was started, or rats remained untreated and were followed a further 56 days for a total of 84 days. Half of the untreated rats had quinapril started 3 days prior to sacrifice, on day 81. Starting quinapril at either 28 or 81 days had little effect on cardiac hemodynamics, or ventricular remodeling. Quinapril did however attenuate the MI-induced rise in cardiac cytokine expression (tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta, -5 and -6). Thus, in CHF, ACE inhibitors attenuate the rise in cardiac cytokine expression. This study helps to identify a new mechanism by which ACE inhibitors may exert their beneficial effects in CHF. PMID:12085975

  15. Evaluation of right ventricular remodeling using cardiac magnetic resonance imaging in co-existent chronic obstructive pulmonary disease and obstructive sleep apnea.

    PubMed

    Sharma, Bhavneesh; Neilan, Tomas G; Kwong, Raymond Y; Mandry, Damien; Owens, Robert L; McSharry, David; Bakker, Jessie P; Malhotra, Atul

    2013-02-01

    Untreated chronic obstructive pulmonary disease (COPD) co-existing with obstructive sleep apnea (OSA), also known as overlap syndrome, has higher cardiovascular mortality than COPD alone but its underlying mechanism remains unclear. We hypothesize that the presence of overlap syndrome is associated with more extensive right ventricular (RV) remodeling compared to patients with COPD alone. Adult COPD patients (GOLD stage 2 or higher) with at least 10 pack-years of smoking history were included. Overnight laboratory-based polysomnography was performed to test for OSA. Subjects with an apnea-hypopnea index (AHI) >10/h were classified as having overlap syndrome (n = 7), else classified as having COPD-only (n = 11). A cardiac MRI was performed to assess right and left cardiac chambers sizes, ventricular masses, and cine function. RV mass index (RVMI) was markedly higher in the overlap group than the COPD-only group (19 ± 6 versus 11 ± 6; p = 0.02). Overlap syndrome subjects had a reduced RV remodeling index (defined as the ratio between RVMI and RV end-diastolic volume index) compared to the COPD-only group (0.27 ± 0.06 versus 0.18 ± 0.08; p = 0.02). In the overlap syndrome subjects, the extent of RV remodeling was associated with severity of oxygen desaturation (R(2) = 0.65, p = 0.03). Our pilot results suggest that untreated overlap syndrome may cause more extensive RV remodeling than COPD alone. PMID:23272670

  16. Traditional Formula, Modern Application: Chinese Medicine Formula Sini Tang Improves Early Ventricular Remodeling and Cardiac Function after Myocardial Infarction in Rats

    PubMed Central

    Liu, Jiangang; Peter, Karoline; Shi, Dazhuo; Zhang, Lei; Dong, Guoju; Zhang, Dawu; Breiteneder, Heimo; Ma, Yan

    2014-01-01

    Sini Tang (SNT) is a traditional Chinese herbal formula consisting of four different herbs: the root of Aconitum carmichaelii, the bark of Cinnamomum cassia, the rhizome of Zingiber officinale, and the root of Glycyrrhiza uralensis. This study aims to evaluate the improvement of early ventricular remodeling and cardiac function in myocardial infarction (MI) rats by SNT. A MI model was established by ligation of the left anterior descending coronary artery. Following treatment for 4 weeks, ultrasonic echocardiography was performed. Myocardial histopathological changes were observed using haematoxylin and eosin staining. Collagens (type I and type III), transforming growth factor-β1 (TGF-β1), and Toll-like receptors (TLR-2 and TLR-4) were measured in plasma, serum, and myocardial tissue. SNT treatment decreased the infarct size, the left ventricular cavity area/heart cavity area ratio, and the left ventricle dimension at end systole and increased the left ventricular ejection fraction. SNT reduced the levels of TLR-2 and TLR-4 in myocardial tissue significantly and decreased the collagens content in serum and in myocardial tissue. SNT could partially reduce the level of TGF-β1 in serum and in myocardial tissue. Our data suggest that the Chinese medicine formula SNT has the potential to improve early ventricular remodeling and cardiac function after MI. PMID:24971143

  17. Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure

    PubMed Central

    Goss, Kara N.; Cucci, Anthony R.; Fisher, Amanda J.; Albrecht, Marjorie; Frump, Andrea; Tursunova, Roziya; Gao, Yong; Brown, Mary Beth; Petrache, Irina; Tepper, Robert S.; Ahlfeld, Shawn K.

    2015-01-01

    The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0–4 or 0–10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm = 362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults. PMID:25659904

  18. Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure.

    PubMed

    Goss, Kara N; Cucci, Anthony R; Fisher, Amanda J; Albrecht, Marjorie; Frump, Andrea; Tursunova, Roziya; Gao, Yong; Brown, Mary Beth; Petrache, Irina; Tepper, Robert S; Ahlfeld, Shawn K; Lahm, Tim

    2015-04-15

    The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0-4 or 0-10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm = 362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults. PMID:25659904

  19. Weight loss and progressive left ventricular remodelling: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Shah, Ravi V; Murthy, Venkatesh L; Abbasi, Siddique A; Eng, John; Wu, Colin; Ouyang, Pamela; Kwong, Raymond Y; Goldfine, Allison; Bluemke, David A; Lima, Joao; Jerosch-Herold, Michael

    2016-01-01

    Aims Impact of weight loss on cardiac structure has not been extensively investigated in large, multi-ethnic, community-based populations. We investigated the longitudinal impact of weight loss on cardiac structure by cardiac magnetic resonance (CMR). Methods and results 2351 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent CMR at Exam 1 (2002) and Exam 5 (2011) were included. Primary outcomes were percentage change in LV mass (indexed to height) and LV mass-to-volume ratio (concentric LV remodelling). Multivariable linear regression was used to measure the association between outcomes and weight change. At median 9.4 years' follow-up, 639 individuals (27%) experienced >5% weight loss (median 6.9 kg) and 511 (22%) had >5% weight gain (median 6.4 kg). A >5% weight gain was associated with the greatest increase in LV mass (+5.4% median) and LV mass-to-volume ratio (+12.2% median). Adjusting for medications, hypertension/diabetes (and change in these risk factors), age, race and other risk factors, every 5% weight loss was associated with a 1.3% decrease in height-indexed LV mass and 1.3% decrease in LV mass-to-volume ratio (p <0.0001). There was no effect modification/confounding by age, race, gender or baseline BMI. Change in LV mass-to-volume ratio was roughly linear, specifically for modest degrees of weight loss (−10% to +10%). Change in LV mass was linear with weight loss, suggesting no threshold of weight loss is needed for LV mass regression. Conclusions In a large multi-ethnic population, weight loss is associated with beneficial effects on cardiac structure, independent of age, race, gender, BMI and obesity-related cardiometabolic risk. There is no threshold of weight loss required to produce these effects. PMID:25009171

  20. Left ventricular remodeling during and after 60 days of sedentary head-down bed rest.

    PubMed

    Westby, Christian M; Martin, David S; Lee, Stuart M C; Stenger, Michael B; Platts, Steven H

    2016-04-15

    Short periods of weightlessness are associated with reduced stroke volume and left ventricular (LV) mass that appear rapidly and are thought to be largely dependent on plasma volume. The magnitude of these cardiac adaptations are even greater after prolonged periods of simulated weightlessness, but the time course during and the recovery from bed rest has not been previously described. We collected serial measures of plasma volume (PV, carbon monoxide rebreathing) and LV structure and function [tissue Doppler imaging, three-dimensional (3-D) and 2-D echocardiography] before, during, and up to 2 wk after 60 days of 6° head down tilt bed rest (HDTBR) in seven healthy subjects (four men, three women). By 60 days of HDTBR, PV was markedly reduced (2.7 ± 0.3 vs. 2.3 ± 0.3 liters,P< 0.001). Resting measures of LV volume and mass were ∼15% (P< 0.001) and ∼14% lower (P< 0.001), respectively, compared with pre-HDTBR values. After 3 days of reambulation, both PV and LV volumes were not different than pre-HDTBR values. However, LV mass did not recover with normalization of PV and remained 12 ± 4% lower than pre-bed rest values (P< 0.001). As previously reported, decreased PV and LV volume precede and likely contribute to cardiac atrophy during prolonged LV unloading. Although PV and LV volume recover rapidly after HDTBR, there is no concomitant normalization of LV mass. These results demonstrate that reduced LV mass in response to prolonged simulated weightlessness is not a simple effect of tissue dehydration, but rather true LV muscle atrophy that persists well into recovery. PMID:26494448

  1. Follistatin-like 1 in Chronic Systolic Heart Failure: A Marker of Left Ventricular Remodeling

    PubMed Central

    El-Armouche, Ali; Ouchi, Noriyuki; Tanaka, Komei; Doros, Gheorghe; Wittköpper, Katrin; Schulze, Thomas; Eschenhagen, Thomas; Walsh, Kenneth; Sam, Flora

    2011-01-01

    Background Follistatin-like 1 (FSTL1) is an extracellular glycoprotein that is found in human serum. Recent work suggests that FSTL1 is secreted in response to ischemic injuries and that its overexpression is protective in the heart and vasculature. Methods and Results Here, we examined serum FSTL1 levels in patients with chronic heart failure with left ventricular (LV) ejection fraction <40% (n=86). The distribution of the sample, from these chronic heart failure patients, was separated into three tertiles of low, medium and high FSTL1 levels. Serum FSTL1 levels were increased 56% above age- and gender-matched, healthy controls. Diabetes mellitus, brain natriuretic peptide level, left atrial size, LV posterior wall thickness, LV end-diastolic diameter and LV mass were significant determinants of FSTL1 serum levels by bivariate analysis. After controlling for significant covariates, FSTL1 levels predicted LV hypertrophy (as measured by LV mass index) by multivariate linear regression analysis (P<0.001). Unadjusted survival analysis demonstrated increased mortality in patients with increasing FSTL1 levels (P=0.09). After adjusting for significant parameters, patients with increased FSTL1 remained at the highest risk of death [hazard ratio (95% confidence limits) 1.028, (0.98 and 1.78)]; (P=0.26). To determine whether elevated FSTL1 may be derived from the myocardium, FSTL1 protein expression was measured in samples from explanted, failing (n=18) and non-failing human hearts (n=7). LV failing hearts showed 2.5-fold higher FSTL1 protein levels than non-failing control hearts (P<0.05). Conclusions Elevated serum FSTL1 in human heart failure patients was associated with LV hypertrophy. Further studies on the role of FSTL1 as a biomarker in chronic systolic heart failure are warranted. PMID:21622850

  2. Comprehensive Annular and Subvalvular Repair of Chronic Ischemic Mitral Regurgitation Improves Long-Term Results With the Least Ventricular Remodeling

    PubMed Central

    Szymanski, Catherine; Bel, Alain; Cohen, Iris; Touchot, Bernard; Handschumacher, Mark D.; Desnos, Michel; Carpentier, Alain; Menasché, Philippe; Hagège, Albert A.; Levine, Robert A.; Messas, Emmanuel

    2012-01-01

    Background Undersized ring annuloplasty for ischemic mitral regurgitation (MR) is associated with variable results and >30% MR recurrence. We tested whether subvalvular repair by severing second-order mitral chordae can improve annuloplasty by reducing papillary muscle tethering. Methods and Results Posterolateral myocardial infarction known to produce chronic remodeling and MR was created in 28 sheep. At 3 months, sheep were randomized to sham surgery versus isolated undersized annuloplasty versus isolated bileaflet chordal cutting versus the combined therapy (n=7 each). At baseline, chronic myocardial infarction (3 months), and euthanasia (6.6 months), we measured left ventricular (LV) volumes and ejection fraction, wall motion score index, MR regurgitation fraction and vena contracta, mitral annulus area, and posterior leaflet restriction angle (posterior leaflet to mitral annulus area) by 2-dimensional and 3-dimensional echocardiography. All groups were comparable at baseline and chronic myocardial infarction, with mild to moderate MR (MR vena contracta, 4.6±0.1 mm; MR regurgitation fraction, 24.2±2.9%) and mitral annulus dilatation (P<0.01). At euthanasia, MR progressed to moderate to severe in controls but decreased to trace with ring plus chordal cutting versus trace to mild with chordal cutting alone versus mild to moderate with ring alone (MR vena contracta, 5.9±1.1 mm in controls, 0.5±0.08 with both, 1.0±0.9 with chordal cutting alone, 2.0±0.7 with ring alone; P<0.01). In addition, LV end-systolic volume increased by 108% in controls versus 28% with ring plus chordal cutting, less than with each intervention alone (P<0.01). In multivariate analysis, LV end-systolic volume and mitral annulus area most strongly predicted MR (r2=0.82, P<0.01). Conclusions Comprehensive annular and subvalvular repair improves long-term reduction of both chronic ischemic MR and LV remodeling without decreasing global or segmental LV function at follow-up. PMID:23139296

  3. Ischaemic mitral regurgitation: The effects of ring annuloplasty and suture annuloplasty repair techniques on left ventricular re-remodeling

    PubMed Central

    Aydin, Cemalettin; Kara, Ibrahim; Ay, Yasin; Inan, Bekir; Basel, Halil; Yanartas, Mehmet; Zeybek, Rahmi

    2013-01-01

    Objective: To examine the mid-term results of patients on whom a coronary revascularization as well as a mitral ring and suture annuloplasty have been performed due to coronary artery disease (CAD) and ischaemic mitral regurgitation (IMR). Methodology: Totally 73 patients on whom a revascularization and a mitral valve repair due to CAD and IMR had been performed in our clinic between 2000-2008 were included in the study. Patients were divided into two groups one of which included 38 patients (52.05%) on whom a coronary artery bypass graft (CABG) and a ring annuloplasty on the mitral valve had been performed (Group 1) and the other one 35 patients (47.95%) on whom only suture annuloplasty as well as a CABG had been performed (Group 2). The study was planned retrospectively and study data have been obtained by screening the hospital registries retrospectively. In the mid-term, patients were invited for a check and their intragroup and intergroup echocardiographic parameters and functional capacities were assessed statistically. Results: In pre-operational and post-operational intragroup assessment in terms of echocardiographic findings; although LVEDD, LVESD, EDV, PAP and the degree of recurrent MR have been decreased in both groups, the decrease in LVESD and PAP and the low degree of recurrent MR were statistically significant in Group 1 patients (p=0.047, p=0.023, p=0.01, respectively). When the mid-term intergroup echocardiograpic findings were assessed; PAP and recurrent MR have been determined statistically lower in Group 1 patients (p=0.005, p=0.08, respectively). The length of intensive care unit stay, length of hospitalization and length of detachment from respiratory support were statistically significantly longer in ring annuloplasty performed group (p=0.012, p=0.033, p=0.029, respectively). Conclusions: In moderate to severe IMR patients, a positive contribution can be provided to ventricular remodeling by a ring annuloplasty through a significant decrease

  4. Adverse outcome of using tilmicosin in a lamb with multiple ventricular septal defects

    PubMed Central

    Christodoulopoulos, Georgios

    2009-01-01

    A 15-day-old, 6.08 kg, lamb was injected subcutaneously with tilmicosin 15 mg/kg body weight. Approximately 15 min later, the lamb died. During necropsy, the heart was found to have multiple ventricular septal defects. Death was attributed to sudden heart failure due to the cardiac effects of tilmicosin in a heart having congenital defects. PMID:19337615

  5. Increased systolic load causes adverse remodeling of fetal aortic and mitral valves.

    PubMed

    Tibayan, Frederick A; Louey, Samantha; Jonker, Sonnet; Espinoza, Herbert; Chattergoon, Natasha; You, Fanglei; Thornburg, Kent L; Giraud, George

    2015-12-15

    While abnormal hemodynamic forces alter fetal myocardial growth, little is known about whether such insults affect fetal cardiac valve development. We hypothesized that chronically elevated systolic load would detrimentally alter fetal valve growth. Chronically instrumented fetal sheep received either a continuous infusion of adult sheep plasma to increase fetal blood pressure, or a lactated Ringer's infusion as a volume control beginning on day 126 ± 4 of gestation. After 8 days, mean arterial pressure was higher in the plasma infusion group (63.0 mmHg vs. 41.8 mmHg, P < 0.05). Mitral annular septal-lateral diameter (11.9 mm vs. 9.1 mm, P < 0.05), anterior leaflet length (7.7 mm vs. 6.4 mm, P < 0.05), and posterior leaflet length (P2; 4.0 mm vs. 3.0 mm, P < 0.05) were greater in the elevated load group. mRNA levels of Notch-1, TGF-β2, Wnt-2b, BMP-1, and versican were suppressed in aortic and mitral valve leaflets; elastin and α1 type I collagen mRNA levels were suppressed in the aortic valves only. We conclude that sustained elevated arterial pressure load on the fetal heart valve leads to anatomic remodeling and, surprisingly, suppression of signaling and extracellular matrix genes that are important to valve development. These novel findings have important implications on the developmental origins of valve disease and may have long-term consequences on valve function and durability. PMID:26354842

  6. Resveratrol attenuates left ventricular remodeling in old rats with COPD induced by cigarette smoke exposure and LPS instillation.

    PubMed

    Hu, Yi Xin; Cui, Hua; Fan, Li; Pan, Xiu Jie; Wu, Ji Hua; Shi, Suo Zhu; Cui, Shao Yuan; Wei, Zhi Min; Liu, Lin

    2013-12-01

    The objective of this study was to investigate left cardiac damage and the cardioprotective effects of resveratrol in old rats with COPD. Rats 22 months old were divided into three groups: control (CTL), smoking and lipopolysaccharides (SM/LPS), and SM/LPS plus resveratrol (SM/LPS-Res). Cardiac function, pathology, oxidative stress, and apoptosis index were measured. Expression of myocardial SIRT1 was studied by real-time quantitative polymerase chain reaction (PCR) and Western blot detection. The heart weight-body weight ratio (LVW/BW) increased in the SM/LPS group compared with the CTL group. Both the LVW/BW and the area of fibrosis in the SM/LPS-Res group decreased compared with those in the SM/LPS group. 8-OHdG expression increased in cardiac tissue of rats in the SM/LPS group, which could be inhibited by resveratrol. Resveratrol significantly increased the activity of superoxide dismutase (SOD) and reduced the cardiac malonyldialdehyde (MDA) level in the SM/LPS-Res group. There was a significant decrease in the extent of cardiomyocyte apoptosis in the SM/LPS-Res group compared with the SM/LPS group. SIRT1 mRNA increased in the SM/LPS-Res group compared with the SM/LPS group. In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD). PMID:24289075

  7. Cardio-protecteffect of qiliqiangxin capsule on left ventricular remodeling, dysfunction and apoptosis in heart failure rats after chronic myocardial infarction

    PubMed Central

    Liang, Tuo; Zhang, Yuhui; Yin, Shijie; Gan, Tianyi; An, Tao; Zhang, Rongcheng; Wang, Yunhong; Huang, Yan; Zhou, Qiong; Zhang, Jian

    2016-01-01

    Background: Qiliqiangxin (QL) capsule is a traditional Chinese medicine which has been approved for the treatment of chronic heart failure. Evidences proved that QL capsules further reduced the NT-proBNP levels and improved left ventricular ejection fraction in CHF patients but the evidence supporting its underlying mechanism is still unclear. Methods and Results: Myocardial infarction (MI) -Heart failure (HF) Sprague-Dawley ratsmodel and neonatal rat cardiac myocytes (NRCMs) were used. Animals were assigned into 4 groups, normal group (n=6), shame-operation group (n=6), MI rats 4 weeks after left anterior descending coronary artery ligation were randomized into vehicle group (n=8), QL group (n=8). QL significantly attenuated cardiac dysfunction and ventricle remodeling as echocardiography and hemodynamic measurements showed improvement in left ventricular ejection fraction, fractional shortening, ±dp/dt and left ventricular end diastolic and systolic diameters in QL treated group compared with the vehicle group. Improvements ininterstitial fibrosisand mitochondrial structures were also exhibited by Sirius Red staining, RT-PCR and electron microscopy. QL treatment improved apoptosis and VEGF expression in rats marginal infract area. Complementary experiments analyzed the improved apoptosis and up-regulate of VEGF in ischemia-hypoxia cultivated NRCMs is in an Akt dependent manner and can be reversed by Akt inhibitor. Conclusion: QL capsule can improve cardiac dysfunction and ventricular remodeling in MI-HF ratsmodel, this cardiac protective efficacy may be concerned with attenuated apoptosis and cardiac fibrosis. Up-regulated VEGF expression and Akt phosphorylation may take part in this availability. PMID:27347313

  8. Relationship between myocardial flow reserve by oxygen-15 water positron emission tomography in the subacute phase of myocardial infarction and left ventricular remodeling in the chronic phase.

    PubMed

    Ohara, Minako; Yukiiri, Kazushi; Masugata, Hisashi; Iwado, Yasuyoshi; Takinami, Hiroyuki; Nishiyama, Yoshihiro; Ohkawa, Motoomi; Senda, Shoichi; Ohmori, Koji; Kohno, Masakazu

    2008-07-01

    The purposes of this study were to examine the effects of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) on myocardial flow reserve in patients with acute myocardial infarction (AMI) in the subacute phase using oxygen-15 positron emission tomography (PET) and to elucidate the relationship between the myocardial flow reserve and remodeling in the chronic phase. Sixty patients who had been treated with coronary angioplasty within 12 h after the onset of AMI were enrolled. Patients were divided into an enalapril (ACEI) group and a candesartan (ARB) group. The myocardial flow reserve was measured by oxygen-15 water PET in the subacute phase from the 20th to the 30th day after the onset of AMI. Left ventriculography was performed to measure the left ventricular ejection fraction in the chronic phase about 6 months after the onset. Ten patients (33%) in the enalapril group and 4 patients (13%) in the candesartan group stopped taking their respective medications within a few days of starting, because of side effects such as cough or hypotension. Thus, the prevalence of medication intolerance was higher in the enalapril group. The myocardial flow reserve in the subacute phase and the left ventricular ejection fraction in the chronic phase were lower in the enalapril group (2.08 +/- 0.30 and 42 +/- 6%) than in the candesartan group (2.25 +/- 0.20 and 49 +/- 5%) (p < 0.05). The myocardial flow reserve significantly correlated with the left ventricular ejection fraction in all patients (r = 0.45, p < 0.01). The myocardial flow reserve assessed by PET in the subacute phase after AMI was found to be related to left ventricular remodeling in the chronic phase. PMID:18957800

  9. Intravenous myocardial contrast echocardiography predicts regional and global left ventricular remodelling after acute myocardial infarction: comparison with low dose dobutamine stress echocardiography

    PubMed Central

    Abe, Y; Muro, T; Sakanoue, Y; Komatsu, R; Otsuka, M; Naruko, T; Itoh, A; Yoshiyama, M; Haze, K; Yoshikawa, J

    2005-01-01

    Objective: To assess the role of intravenous myocardial contrast echocardiography (MCE) in predicting functional recovery and regional or global left ventricular (LV) remodelling after acute myocardial infarction (AMI) compared with low dose dobutamine stress echocardiography (LDSE). Methods: 21 patients with anterior AMI and successful primary angioplasty underwent MCE and LDSE during the subacute stage (2–4 weeks after AMI). Myocardial perfusion and contractile reserve were assessed in each segment (12 segment model) with MCE and LDSE. The 118 dyssynergic segments in the subacute stage were classified as recovered, unchanged, or remodelled according to wall motion at six months’ follow up. Percentage increase in LV end diastolic volume (%ΔEDV) was also calculated. Results: The presence of perfusion was less accurate than the presence of contractile reserve in predicting regional recovery (55% v 81%, p < 0.0001). However, the absence of perfusion was more accurate than the absence of contractile reserve in predicting regional remodelling (83% v 48%, p < 0.0001). The number of segments without perfusion was an independent predictor of %ΔEDV, whereas the number of segments without contractile reserve was not. The area under the receiver operating characteristic curve showed that the number of segments without perfusion predicted substantial LV dilatation (%ΔEDV > 20%) more accurately than did the number of segments without contractile reserve (0.88 v 0.72). Conclusion: In successfully revascularised patients with AMI, myocardial perfusion assessed by MCE is predictive of regional and global LV remodelling rather than of functional recovery, whereas contractile reserve assessed by LDSE is predictive of functional recovery rather than of LV remodelling. PMID:15797931

  10. Qishenyiqi Protects Ligation-Induced Left Ventricular Remodeling by Attenuating Inflammation and Fibrosis via STAT3 and NF-κB Signaling Pathway

    PubMed Central

    Shi, Tianjiao; Wu, Yan; Han, Jing; Chai, Xingyun; Wang, Wei

    2014-01-01

    Aim Qi-shen-yi-qi (QSYQ), a formula used for the routine treatment of heart failure (HF) in China, has been demonstrated to improve cardiac function through down-regulating the activation of the Renin-Angiotensin-Aldosterone System (RAAS). However, the mechanisms governing its therapeutic effects are largely unknown. The present study aims to demonstrate that QSYQ treatment can prevent left ventricular remodeling in heart failure by attenuating oxidative stress and inhabiting inflammation. Methods Sprague-Dawley (SD) rats were randomly divided into 6 groups: sham group, model group (LAD coronary artery ligation), QSYQ group with high dosage, middle dosage and low dosage (LAD ligation and treated with QSYQ), and captopril group (LAD ligation and treated with captopril as the positive drug). Indicators of fibrosis (Masson, MMPs, and collagens) and inflammation factors were detected 28 days after surgery. Results Results of hemodynamic alterations (dp/dt value) in the model group as well as other ventricular remodeling (VR) markers, such as MMP-2, MMP-9, collagen I and III elevated compared with sham group. VR was accompanied by activation of RAAS (angiotensin II and NADPHoxidase). Levels of pro-inflammatory cytokines (TNF-α, IL-6) in myocardial tissue were also up-regulated. Treatment of QSYQ improved cardiac remodeling through counter-acting the aforementioned events. The improvement of QSYQ was accompanied with a restoration of angiotensin II-NADPHoxidase-ROS-MMPs pathways. In addition, “therapeutic” QSYQ administration can reduce both TNF-α-NF-B and IL-6-STAT3 pathways, respectively, which further proves the beneficial effects of QSYQ. Conclusions Our study demonstrated that QSYQ protected LAD ligation-induced left VR via attenuating AngII -NADPH oxidase pathway and inhabiting inflammation. These findings provide evidence as to the cardiac protective efficacy of QSYQ to HF and explain the beneficial effects of QSYQ in the clinical application for HF. PMID

  11. Combined score using clinical, electrocardiographic, and echocardiographic parameters to predict left ventricular remodeling in patients having had cardiac resynchronization therapy six months earlier.

    PubMed

    Brunet-Bernard, Anne; Maréchaux, Sylvestre; Fauchier, Laurent; Guiot, Aurélie; Fournet, Maxime; Reynaud, Amélie; Schnell, Frédéric; Leclercq, Christophe; Mabo, Philippe; Donal, Erwan

    2014-06-15

    The aim of this study was to evaluate whether a scoring system integrating clinical, electrocardiographic, and echocardiographic measurements can predict left ventricular reverse remodeling after cardiac resynchronization therapy (CRT). The derivation cohort consisted of 162 patients with heart failure implanted with a CRT device. Baseline clinical, electrocardiographic, and echocardiographic characteristics were entered into univariate and multivariate models to predict reverse remodeling as defined by a ≥15% reduction in left ventricular end-systolic volume at 6 months (60%). Combinations of predictors were then tested under different scoring systems. A new 7-point CRT response score termed L2ANDS2: Left bundle branch block (2 points), Age >70 years, Nonischemic origin, left ventricular end-diastolic Diameter <40 mm/m(2), and Septal flash (2 points) was calculated for these patients. This score was then validated against a validation cohort of 45 patients from another academic center. A highly significant incremental predictive value was noted when septal flash was added to an initial 4-factor model including left bundle branch block (difference between area under the curve C statistics = 0.125, p <0.001). The predictive accuracy using the L2ANDS2 score was then 0.79 for the C statistic. Application of the new score to the validation cohort (71% of responders) gave a similar C statistic (0.75). A score >5 had a high positive likelihood ratio (+LR = 5.64), whereas a score <2 had a high negative likelihood ratio (-LR = 0.19). In conclusion, this L2ANDS2 score provides an easy-to-use tool for the clinician to assess the pretest probability of a patient being a CRT responder. PMID:24793667

  12. Left ventricular concentric geometry during treatment adversely affects cardiovascular prognosis in hypertensive patients.

    PubMed

    Muiesan, Maria Lorenza; Salvetti, Massimo; Monteduro, Cristina; Bonzi, Bianca; Paini, Anna; Viola, Sara; Poisa, Paolo; Rizzoni, Damiano; Castellano, Maurizio; Agabiti-Rosei, Enrico

    2004-04-01

    Left ventricular (LV) mass and geometry predict risk for cardiovascular events in hypertension. Regression of LV hypertrophy (LVH) may imply an important prognostic significance. The relation between changes in LV geometry during antihypertensive treatment and subsequent prognosis has not yet been determined. A total of 436 prospectively identified uncomplicated hypertensive subjects with a baseline and follow-up echocardiogram (last examination 72+/-38 months apart) were followed for an additional 42+/-16 months. Their family doctor gave antihypertensive treatment. After the last follow-up echocardiogram, a first cardiovascular event occurred in 71 patients. Persistence of LVH from baseline to follow-up was confirmed as an independent predictor of cardiovascular events. Cardiovascular morbidity and mortality were significantly greater in patients with concentric (relative wall thickness > or =0.44) than in those with eccentric geometry (relative wall thickness <0.44) in patients presenting with LVH (P=0.002) and in those without LVH (P=0.002) at the follow-up echocardiogram. The incidence of cardiovascular events progressively increased from the first to the third tertile of LV mass index at follow-up (partition values 91 and 117 g/m2), but for a similar value of LV mass index it was significantly greater in those with concentric geometry (OR: 4.07; 95% CI: 1.49 to 11.14; P=0.004 in the second tertile; OR: 3.45; 95% CI: 1.62 to 7.32; P=0.001 in the third tertile; P<0.0001 in concentric versus eccentric geometry). Persistence or development of concentric geometry during follow-up may have additional prognostic significance in hypertensive patients with and without LVH. PMID:15007041

  13. Left Ventricular Geometry and Blood Pressure as Predictors of Adverse Progression of Fabry Cardiomyopathy

    PubMed Central

    Krämer, Johannes; Bijnens, Bart; Störk, Stefan; Ritter, Christian O.; Liu, Dan; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2015-01-01

    Background In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated. Methods In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed. Results Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05). Conclusions LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy. PMID:26600044

  14. Cardiac CaM Kinase II Genes δ and γ Contribute to Adverse Remodeling but Redundantly Inhibit Calcineurin-Induced Myocardial Hypertrophy

    PubMed Central

    Kreusser, Michael M.; Lehmann, Lorenz H.; Keranov, Stanislav; Hoting, Marc-Oscar; Oehl, Ulrike; Kohlhaas, Michael; Reil, Jan-Christian; Neumann, Kay; Schneider, Michael D.; Hill, Joseph A.; Dobrev, Dobromir; Maack, Christoph; Maier, Lars S.; Gröne, Hermann-Josef; Katus, Hugo A.; Olson, Eric N.; Backs, Johannes

    2014-01-01

    Background Ca2+-dependent signaling through CaM Kinase II (CaMKII) and calcineurin was suggested to contribute to adverse cardiac remodeling. However, the relative importance of CaMKII versus calcineurin for adverse cardiac remodeling remained unclear. Methods and Results We generated double-knockout mice (DKO) lacking the 2 cardiac CaMKII genes δ and γ specifically in cardiomyocytes. We show that both CaMKII isoforms contribute redundantly to phosphorylation not only of phospholamban, ryanodine receptor 2, and histone deacetylase 4, but also calcineurin. Under baseline conditions, DKO mice are viable and display neither abnormal Ca2+ handling nor functional and structural changes. On pathological pressure overload and β-adrenergic stimulation, DKO mice are protected against cardiac dysfunction and interstitial fibrosis. But surprisingly and paradoxically, DKO mice develop cardiac hypertrophy driven by excessive activation of endogenous calcineurin, which is associated with a lack of phosphorylation at the auto-inhibitory calcineurin A site Ser411. Likewise, calcineurin inhibition prevents cardiac hypertrophy in DKO. On exercise performance, DKO mice show an exaggeration of cardiac hypertrophy with increased expression of the calcineurin target gene RCAN1-4 but no signs of adverse cardiac remodeling. Conclusions We established a mouse model in which CaMKII’s activity is specifically and completely abolished. By the use of this model we show that CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin-dependent hypertrophy. These data suggest inhibition of CaMKII but not calcineurin as a promising approach to attenuate the progression of heart failure. PMID:25124496

  15. A state of reversible compensated ventricular dysfunction precedes pathological remodelling in response to cardiomyocyte-specific activity of angiotensin II type-1 receptor in mice

    PubMed Central

    Frentzou, Georgia A.; Drinkhill, Mark J.; Turner, Neil A.; Ball, Stephen G.; Ainscough, Justin F. X.

    2015-01-01

    ABSTRACT Cardiac dysfunction is commonly associated with high-blood-pressure-induced cardiomyocyte hypertrophy, in response to aberrant renin-angiotensin system (RAS) activity. Ensuing pathological remodelling promotes cardiomyocyte death and cardiac fibroblast activation, leading to cardiac fibrosis. The initiating cellular mechanisms that underlie this progressive disease are poorly understood. We previously reported a conditional mouse model in which a human angiotensin II type-I receptor transgene (HART) was expressed in differentiated cardiomyocytes after they had fully matured, but not during development. Twelve-month-old HART mice exhibited ventricular dysfunction and cardiomyocyte hypertrophy with interstitial fibrosis following full receptor stimulation, without affecting blood pressure. Here, we show that chronic HART activity in young adult mice causes ventricular dysfunction without hypertrophy, fibrosis or cardiomyocyte death. Dysfunction correlated with reduced expression of pro-hypertrophy markers and increased expression of pro-angiogenic markers in the cardiomyocytes experiencing increased receptor load. This stimulates responsive changes in closely associated non-myocyte cells, including the downregulation of pro-angiogenic genes, a dampened inflammatory response and upregulation of Tgfβ. Importantly, this state of compensated dysfunction was reversible. Furthermore, increased stimulation of the receptors on the cardiomyocytes caused a switch in the secondary response from the non-myocyte cells. Progressive cardiac remodelling was stimulated through hypertrophy and death of individual cardiomyocytes, with infiltration, proliferation and activation of fibroblast and inflammatory cells, leading to increased angiogenic and inflammatory signalling. Together, these data demonstrate that a state of pre-hypertrophic compensated dysfunction can exist in affected individuals before common markers of heart disease are detectable. The data also suggest that

  16. Swine model of chronic postcapillary pulmonary hypertension with right ventricular remodeling: long-term characterization by cardiac catheterization, magnetic resonance, and pathology.

    PubMed

    Pereda, Daniel; García-Alvarez, Ana; Sánchez-Quintana, Damián; Nuño, Mario; Fernández-Friera, Leticia; Fernández-Jiménez, Rodrigo; García-Ruíz, José Manuel; Sandoval, Elena; Aguero, Jaume; Castellá, Manuel; Hajjar, Roger J; Fuster, Valentín; Ibáñez, Borja

    2014-07-01

    Pulmonary hypertension (PH) is prevalent and carries high morbidity and mortality, mostly due to right ventricular (RV) dysfunction. Postcapillary PH is the most frequent form but there are no large-animal models available. We developed and characterized a porcine model of postcapillary PH by non-restrictive banding of the confluent of both inferior pulmonary veins (n = 10; sham controls n = 3). Right heart catheterization and magnetic resonance were performed before the procedure and monthly during 4 months. All banded animals developed PH. Compared to controls, banded animals presented higher mean pulmonary artery pressure [median (first to third quartile) 30 mmHg (25-37) vs. 20 mmHg (18-23); p = 0.018] and higher pulmonary vascular resistance [5.2 WU (3.8-7.1) vs. 2.3 WU (2.1-3.5); p = 0.028] after 2 months. Differences in indexed RV end-systolic volume [42 mL/m(2) (36-53) vs. 24 mL/m(2) (24-33); p = 0.028] and RV ejection fraction [59 % (54-63) vs. 66 % (64-68); p = 0.028] were also significant after 2 months. Differences remained significant throughout the study. Histopathology revealed increased lung weight and fibrosis but no increase in average water content. Also, remodeling on pulmonary arteries including increased medial and intimal thickness and fibrosis and RV myocardial disarray and fibrosis was demonstrated. Lung remodeling findings were similar in all pulmonary lobes. PMID:24771313

  17. Long-Term Left Ventricular Remodelling in Rat Model of Nonreperfused Myocardial Infarction: Sequential MR Imaging Using a 3T Clinical Scanner

    PubMed Central

    Saleh, Muhammad G.; Sharp, Sarah-Kate; Alhamud, Alkathafi; Spottiswoode, Bruce S.; van der Kouwe, Andre J. W.; Davies, Neil H.; Franz, Thomas; Meintjes, Ernesta M.

    2012-01-01

    Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI. PMID:23118511

  18. The protective effect of microRNA-320 on left ventricular remodeling after myocardial ischemia-reperfusion injury in the rat model.

    PubMed

    Song, Chun-Li; Liu, Bin; Diao, Hong-Ying; Shi, Yong-Feng; Li, Yang-Xue; Zhang, Ji-Chang; Lu, Yang; Wang, Guan; Liu, Jia; Yu, Yun-Peng; Guo, Zi-Yuan; Wang, Jin-Peng; Zhao, Zhuo; Liu, Jian-Gen; Liu, Yi-Hang; Liu, Zhi-Xian; Cai, Dan; Li, Qian

    2014-01-01

    The primary objective of this study investigated the role of microRNA-320 (miR-320) on left ventricular remodeling in the rat model of myocardial ischemia-reperfusion (I/R) injury, and we intended to explore the myocardial mechanism of miR-320-mediated myocardium protection. We collected 120 male Wistar rats (240-280 g) in this study and then randomly divided them into three groups: (1) sham surgery group (sham group: n=40); (2) ischemia-reperfusion model group (I/R group: n=40); and (3) I/R model with antagomir-320 group (I/R+antagomir-320 group: n=40). Value changes of heart function in transesophageal echocardiography were recorded at various time points (day 1, day 3, day 7, day 15 and day 30) after surgery in each group. Myocardial sections were stained with hematoxylin and eosin (H&E) and examined with optical microscope. The degree of myocardial fibrosis was assessed by Sirius Red staining. Terminal dUTP nick end-labeling (TUNEL) and qRT-PCR methods were used to measure the apoptosis rate and to determine the miR-320 expression levels in myocardial tissues. Transesophageal echocardiography showed that the values of left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP) and ±dp/dtmax in the I/R group were obviously lower than those in the sham group, while the left ventricular end-diastolic pressure (LVEDP) value was higher than that in the sham group. The values of LVEF, LVFS, LVSP and ±dp/dtmax showed a gradual decrease in the I/R group, while the LVEDP value showed an up tendency along with the extension of reperfusion time. The H&E staining revealed that rat myocardial tissue in the I/R group presented extensive myocardial damage; for the I/R+antagomir-320 group, however, the degree of damage in myocardial cells was obviously better than that of the I/R group. The Sirius Red staining results showed that the degree of myocardial fibrosis in the I/R group was more severe along

  19. 31P NMR 2D Mapping of Creatine Kinase Forward Flux Rate in Hearts with Postinfarction Left Ventricular Remodeling in Response to Cell Therapy.

    PubMed

    Gao, Ling; Cui, Weina; Zhang, Pengyuan; Jang, Albert; Zhu, Wuqiang; Zhang, Jianyi

    2016-01-01

    Utilizing a fast 31P magnetic resonance spectroscopy (MRS) 2-dimensional chemical shift imaging (2D-CSI) method, this study examined the heterogeneity of creatine kinase (CK) forward flux rate of hearts with postinfarction left ventricular (LV) remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1) A sham-operated normal group (SHAM, n = 6); 2) A 60 minutes distal left anterior descending coronary artery ligation and reperfusion (MI, n = 6); 3) Open patch group; ligation injury plus open fibrin patch over the site of injury (Patch, n = 6); and 4) Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth muscle cells (2 million, each) were injected into the injured myocardium pass through a fibrin patch (Cell+Patch, n = 5). At 4 weeks, the creatine phosphate (PCr)/ATP ratio, CK forward flux rate (Flux PCr→ATP), and k constant of CK forward flux rate (kPCr→ATP) were severely decreased at border zone myocardium (BZ) adjacent to MI. Cell treatment results in significantly increase of PCr/ATP ratio and improve the value of kPCr→ATP and Flux PCr→ATP in BZ myocardium. Moreover, the BZ myocardial CK total activity and protein expression of CK mitochondria isozyme and CK myocardial isozyme were significantly reduced, but recovered in response to cell treatment. Thus, cell therapy results in improvement of BZ bioenergetic abnormality in hearts with postinfarction LV remodeling, which is accompanied by significantly improvements in BZ CK activity and CK isozyme expression. The fast 2D 31P MR CSI mapping can reliably measure the heterogeneity of bioenergetics in hearts with post infarction LV remodeling. PMID:27606901

  20. Partially Silencing Brain Toll-Like Receptor 4 Prevents in Part Left Ventricular Remodeling with Sympathoinhibition in Rats with Myocardial Infarction-Induced Heart Failure

    PubMed Central

    Ogawa, Kiyohiro; Hirooka, Yoshitaka; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

    2013-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions 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. PMID:23874864

  1. Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling

    PubMed Central

    Topkara, Veli K.; Chambers, Kari T.; Yang, Kai-Chien; Tzeng, Huei-Ping; Evans, Sarah; Weinheimer, Carla; Kovacs, Attila; Robbins, Jeffrey; Barger, Philip; Mann, Douglas L.

    2016-01-01

    To elucidate the mechanisms for reverse LV remodeling, we generated a conditional (doxycycline [dox] off) transgenic mouse tetracycline transactivating factor–TRAF2 (tTA-TRAF2) that develops a dilated heart failure (HF) phenotype upon expression of a proinflammatory transgene, TNF receptor–associated factor 2 (TRAF2), and complete normalization of LV structure and function when the transgene is suppressed. tTA-TRAF2 mice developed a significant increase in LV dimension with decreased contractile function, which was completely normalized in the tTA-TRAF2 mice fed dox for 4 weeks (tTA-TRAF2dox4W). Normalization of LV structure and function was accompanied by partial normalization (~60%) of gene expression associated with incident HF. Similar findings were observed in patients with dilated cardiomyopathy who underwent reverse LV remodeling following mechanical circulatory support. Persistence of the HF gene program was associated with an exaggerated hypertrophic response and increased mortality in tTA-TRAF2dox4W mice following transaortic constriction (TAC). These effects were no longer observed following TAC in tTA-TRAF2dox8W, wherein there was a more complete (88%) reversal of the incident HF genes. These results demonstrate that reverse LV remodeling is associated with improvements in cardiac myocyte biology; however, the persistence of the abnormal HF gene program may be maladaptive following perturbations in hemodynamic loading conditions. PMID:27158672

  2. Gender differences in ventricular remodeling and function in college athletes, insights from lean body mass scaling and deformation imaging.

    PubMed

    Giraldeau, Geneviève; Kobayashi, Yukari; Finocchiaro, Gherardo; Wheeler, Matthew; Perez, Marco; Kuznetsova, Tatiana; Lord, Rachel; George, Keith P; Oxborough, David; Schnittger, Ingela; Froelicher, Victor; Liang, David; Ashley, Euan; Haddad, François

    2015-11-15

    Several studies suggest gender differences in ventricular dimensions in athletes. Few studies have, however, made comparisons of data indexed for lean body mass (LBM) using allometry. Ninety Caucasian college athletes (mixed sports) who were matched for age, ethnicity, and sport total cardiovascular demands underwent dual-energy x-ray absorptiometry scan for quantification of LBM. Athletes underwent comprehensive assessment of left and right ventricular and atrial structure and function using 2-dimensional echocardiography and deformation imaging using the TomTec analysis system. The mean age of the study population was 18.9 ± 1.9 years. Female athletes (n = 45) had a greater fat free percentage (19.4 ± 3.7%) compared to male athletes (11.5 ± 3.7%). When scaled to body surface area, male had on average 19 ± 3% (p <0.001) greater left ventricular (LV) mass; in contrast, when scaled to LBM, there was no significant difference in indexed LV mass -1.4 ± 3.0% (p = 0.63). Similarly, when allometrically scaled to LBM, there was no significant gender-based difference in LV or left atrial volumes. Although female athletes had mildly higher LV ejection fraction and LV global longitudinal strain in absolute value, systolic strain rate and allometrically indexed stroke volume were not different between genders (1.5 ± 3.6% [p = 0.63] and 0.0 ± 3.7% [p = 0.93], respectively). There were no differences in any of the functional atrial indexes including strain or strain rate parameters. In conclusion, gender-related differences in ventricular dimensions or function (stroke volume) appear less marked, if not absent, when indexing using LBM allometrically. PMID:26456207

  3. New contribution to the study of ventricular remodeling and valve rings in dilated cardiomyopathy: anatomical and histological evaluation

    PubMed Central

    Dalva, Moise; Correia, Aristides Tadeu; Jatene, Natalia de Freitas; Saldiva, Paulo Hilário Nascimento; Jatene, Fabio Biscegli

    2014-01-01

    Introduction Idiopathic dilated cardiomyopathy causes great impact but many aspects of its pathophysiology remain unknown. Objective To evaluate anatomical and histological aspects of hearts with idiopathic dilated cardiomyopathy and compare them to a control group, evaluating the behavior of the perimeters of the atrioventricular rings and ventricles and to compare the percentage of collagen and elastic fibers of the atrioventricular rings. Methods Thirteen hearts with cardiomyopathy and 13 normal hearts were analysed. They were dissected keeping the ventricular mass and atrioventricular rings, with lamination of segments 20%, 50% and 80% of the distance between the atrioventricular groove and the ventricular apex. The sections were subjected to photo scanning, with measurement of perimeters. The atrioventricular rings were dissected and measured digitally to evaluate their perimeters, later being sent to the pathology laboratory, and stained by hematoxylin-eosin, picrosirius and oxidized resorcin fuccin. Results Regarding to ventricles, dilation occurs in all segments in the pathological group, and the right atrioventricular ring measurement was higher in idiopathic dilated cardiomyopathy group, with no difference in the left side. With respect to collagen, both sides had lower percentage of fibers in the pathological group. With respect to the elastic fibers, there was no difference between the groups. Conclusion There is a change in ventricular geometry in cardiomyopathy group. The left atrioventricular ring does not dilate, in spite of the fact that in both ventricles there is lowering of collagen. PMID:25714199

  4. Prevention of increases in blood pressure and left ventricular mass and remodeling of resistance arteries in young New Zealand genetically hypertensive rats: the effects of chronic treatment with valsartan, enalapril and felodipine.

    PubMed

    Ledingham, J M; Phelan, E L; Cross, M A; Laverty, R

    2000-01-01

    The relative efficacy of three antihypertensive drugs in the prevention of further elevation of blood pressure (BP) and cardiovascular structural remodeling in 4-week-old genetically hypertensive (GH) rats was studied by means of two complementary methods, stereology and myography. Four to 10-week-old GH rats were treated with valsartan (10 mg/kg/day), enalapril (10 mg/kg/day) or felodipine (30 mg/kg/day). Untreated GH and normotensive control rats of Wistar origin served as controls. Tail-cuff systolic SBP was measured weekly and left ventricular (LV) mass determined at the end of the experiment. Mesenteric resistance arteries (MRA) were either fixed by perfusion, embedded in Technovit and sections stained for stereological analysis, or mounted on a wire myograph for structural and functional measurements. BP and LV mass were significantly reduced by all drugs; decreases in BP and LV mass were smaller after felodipine treatment. Valsartan and enalapril caused a decrease in BP to normotensive control values. Felodipine kept BP at the 4-week level and prevented further rise with age. Valsartan caused hypotrophic outward remodeling of MRA, enalapril eutrophic outward remodeling and felodipine hypotrophic remodeling. Myograph measurements showed remodeling of the same order. While all drugs lowered the media/lumen ratio in GH to normal, the outward remodeling after valsartan and enalapril indicates that valsartan and enalapril might be more effective in reversing the inward remodeling of resistance arteries found in essential hypertension. PMID:10754398

  5. Augmentation of Left Ventricular Wall Thickness With Alginate Hydrogel Implants Improves Left Ventricular Function and Prevents Progressive Remodeling in Dogs With Chronic Heart Failure

    PubMed Central

    Sabbah, Hani N.; Wang, Mengjun; Gupta, Ramesh C.; Rastogi, Sharad; Ilsar, Itamar; Sabbah, Michael S.; Kohli, Smita; Helgerson, Sam; Lee, Randall J.

    2013-01-01

    Objectives The study tested the hypothesis that augmentation of the left ventricular (LV) wall thickness with direct intramyocardial injections of alginate hydrogel implants (AHI) reduces LV cavity size, restores LV shape, and improves LV function in dogs with heart failure (HF). Background Progressive LV dysfunction, enlargement, and chamber sphericity are features of HF associated with increased mortality and morbidity. Methods Studies were performed in 14 dogs with HF produced by intracoronary microembolizations (LV ejection fraction [EF] <30%). Dogs were randomized to AHI treatment (n = 8) or to sham-operated control (n = 6). During an open-chest procedure, dogs received either intramyocardial injections of 0.25 to 0.35 ml of alginate hydrogel (Algisyl-LVR, LoneStar Heart, Inc., Laguna Hills, California) or saline. Seven injections were made ∼1.0 to 1.5 cm apart (total volume 1.8 to 2.1 ml) along the circumference of the LV free wall halfway between the apex and base starting from the anteroseptal groove and ending at the posteroseptal groove. Hemodynamic and ventriculographic measurements were made before treatment (PRE) and repeated post-surgery for up to 17 weeks (POST). Results Compared to control, AHI significantly reduced LV end-diastolic and end-systolic volumes and improved LV sphericity. AHI treatment significantly increased EF (26 ± 0.4% at PRE to 31 ± 0.4% at POST; p < 0.05) compared to the decreased EF seen in control dogs (27 ± 0.3% at PRE to 24 ± 1.3% at POST; p < 0.05). AHI treatment was well tolerated and was not associated with increased LV diastolic stiffness. Conclusions In HF dogs, circumferential augmentation of LV wall thickness with AHI improves LV structure and function. The results support continued development of AHI for the treatment of patients with advanced HF. PMID:23998003

  6. Impact on Left Ventricular Function and Remodeling and on 1-Year Outcome in Patients With Left Bundle Branch Block After Transcatheter Aortic Valve Implantation.

    PubMed

    Carrabba, Nazario; Valenti, Renato; Migliorini, Angela; Marrani, Marco; Cantini, Giulia; Parodi, Guido; Dovellini, Emilio Vincenzo; Antoniucci, David

    2015-07-01

    Conflicting results have been reported about the prognostic impact of left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the impact of LBBB after TAVI on left ventricular (LV) function and remodeling and on 1-year outcomes. Of 101 TAVI patients, 9 were excluded. All complications were evaluated according to the Valve Academic Research Consortium 2 definition. Of 92 patients, 34 developed LBBB without more advanced myocardial damage or inflammation biomarkers in comparison with patients without LBBB. The only predictor of new LBBB was larger baseline LV end-diastolic volume. LBBB plus advanced atrioventricular block was strongly correlated with permanent pacemaker implantation (p <0.0001). Patients with LBBB had a higher rate of permanent pacemaker implantation at 30 days (59% vs 19%, p <0.0001) and less recovery of LV systolic function and a trend toward a lower rate of LV reverse remodeling at 1 year. The development of acute kidney injury and the logistic European System for Cardiac Operative Risk Evaluation score were associated with poor outcomes (all-cause mortality and heart failure) (hazard ratio 6.86, 95% confidence interval 2.51 to 18.74, p <0.0001, and hazard ratio 1.04, 95% confidence interval 1.01 to 1.08, p = 0.021, respectively), but not LBBB. In conclusion, after TAVI, 37% of patients developed new LBBB without more advanced myocardial damage or inflammation biomarkers. LBBB was associated with a higher rate of permanent pacemaker implantation, which negatively affected the recovery of LV systolic function. The development of acute kidney injury, rather than LBBB, increases the 1-year risk for mortality and hospitalization for heart failure. PMID:25937352

  7. Exendin-4 attenuates adverse cardiac remodelling in streptozocin-induced diabetes via specific actions on infiltrating macrophages.

    PubMed

    Tate, Mitchel; Robinson, Emma; Green, Brian D; McDermott, Barbara J; Grieve, David J

    2016-01-01

    In addition to its' established metabolic and cardioprotective effects, glucagon-like peptide-1 (GLP-1) reduces post-infarction heart failure via preferential actions on the extracellular matrix (ECM). Here, we investigated whether the GLP-1 mimetic, exendin-4, modulates cardiac remodelling in experimental diabetes by specifically targeting inflammatory/ECM pathways, which are characteristically dysregulated in this setting. Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks. Exendin-4 and insulin improved metabolic parameters in diabetic mice after 12 weeks, but only exendin-4 reduced cardiac diastolic dysfunction and interstitial fibrosis in parallel with altered ECM gene expression. Whilst myocardial inflammation was not evident at 12 weeks, CD11b-F4/80(++) macrophage infiltration at 4 weeks was increased and reduced by exendin-4, together with an improved cytokine profile. Notably, media collected from high glucose-treated macrophages induced cardiac fibroblast differentiation, which was prevented by exendin-4, whilst several cytokines/chemokines were differentially expressed/secreted by exendin-4-treated macrophages, some of which were modulated in STZ exendin-4-treated hearts. Our findings suggest that exendin-4 preferentially protects against ECM remodelling and diastolic dysfunction in experimental diabetes via glucose-dependent modulation of paracrine communication between infiltrating macrophages and resident fibroblasts, thereby indicating that cell-specific targeting of GLP-1 signalling may be a viable therapeutic strategy in this setting. PMID:26597728

  8. Aliskiren and Valsartan Mediate Left Ventricular Remodeling Post-Myocardial Infarction in Mice through MMP-9 Effects

    PubMed Central

    Ramirez, Trevi A.; Iyer, Rugmani Padmanabhan; Ghasemi, Omid; Lopez, Elizabeth F.; Levin, Daniel B.; Zhang, Jianhua; Zamilpa, Rogelio; Chou, Youn-Min; Jin, Yu-Fang; Lindsey, Merry L.

    2014-01-01

    Background We evaluated whether aliskiren, valsartan, or the combination was protective following myocardial infarction (MI) through effects on matrix metalloproteinase (MMP)-9. Methods and Results C57BL/6J wild type (WT, n=94) and MMP-9 null (null, n=85) mice were divided into 4 groups at 3 h post-MI: saline (S), aliskiren (A; 50 mg/kg/d), valsartan (V; 40 mg/kg/d), or A+V and compared to no MI controls at 28 d post-MI. All groups had similar infarct areas, and survival rates were higher in the null mice. The treatments influenced systolic function and hypertrophy index, as well as extracellular matrix (ECM) and inflammatory genes in the remote region, indicating that primary effects were on the viable myocardium. Saline treated WT mice showed increased end systolic and diastolic volumes and hypertrophy index, along with reduced ejection fraction. MMP-9 deletion improved LV function post-MI. Aliskiren attenuated the increase in end systolic volume and hypertrophy index, while valsartan improved end diastolic volumes and aliskiren + valsartan improved the hypertrophy index only when MMP-9 was absent. Extracellular matrix and inflammatory gene expression showed distinct patterns among the treatment groups, indicating a divergence in mechanisms of remodeling. Conclusions This study shows that MMP-9 regulates aliskiren and valsartan effects in mice. These results in mice provide mechanistic insight to help translate these findings to post-MI patients. PMID:24768766

  9. Midlife blood pressure change and left ventricular mass and remodelling in older age in the 1946 British birth cohort study†

    PubMed Central

    Ghosh, Arjun K.; Hardy, Rebecca J.; Francis, Darrel P.; Chaturvedi, Nishi; Pellerin, Denis; Deanfield, John; Kuh, Diana; Mayet, Jamil; Hughes, Alun D.

    2014-01-01

    Aims Antecedent blood pressure (BP) may contribute to cardiovascular disease (CVD) independent of current BP. Blood pressure is associated with left ventricular mass index (LVMI) which independently predicts CVD. We investigated the relationship between midlife BP from age 36 to 64 and LVMI at 60–64 years. Methods and results A total of 1653 participants in the British 1946 Birth Cohort underwent BP measurement and echocardiography aged 60–64. Blood pressure had previously been measured at 36, 43, and 53 years. We investigated associations between BP at each age and rate of change in systolic blood pressure (SBP) between 36–43, 43–53, and 53–60/64 years on LVMI at 60–64 years. Blood pressure from 36 years was positively associated with LVMI. Association with SBP at 53 years was independent of SBP at 60–64 years and other potential confounders (fully adjusted β at 53 years = 0.19 g/m2; 95% CI: 0.11, 0.27; P < 0.001). Faster rates of increase in SBP from 43 to 53 years and 53 to 60/64 years were associated with increased LVMI. Similar relationships were seen for diastolic, pulse, and mean pressure. Rate of increase in SBP between 43–53 years was associated with largest change in LVMI (β at 43–53 years = 3.12 g/m2; 95% CI: 1.53, 4.72; P < 0.001). People on antihypertensive medication (43 years onwards) had greater LVMI even after adjustment for current BP (β at 43 years = 12.36 g/m2; 95% CI: 3.19, 21.53; P = 0.008). Conclusion Higher BP in midlife and rapid rise of SBP in 5th decade is associated with higher LVMI in later life, independent of current BP. People with treated hypertension have higher LVMI than untreated individuals, even accounting for their higher BP. Our findings emphasize importance of midlife BP as risk factor for future CVD. PMID:25246483

  10. Echocardiographic assessment of subclinical left ventricular eccentric hypertrophy in adult-onset GHD patients by geometric remodeling: an observational case-control study

    PubMed Central

    de Gregorio, Cesare; Curtò, Lorenzo; Recupero, Antonino; Grimaldi, Patrizia; Almoto, Barbara; Venturino, Marilena; Cento, Domenico; Narbone, Maria Carola; Trimarchi, Francesco; Coglitore, Sebastiano; Cannavò, Salvatore

    2006-01-01

    Background Most patients with growth hormone deficiency (GHD) show high body mass index. Overweight subjects, but GHD patients, were demonstrated to have high left ventricular mass index (LVMi) and abnormal LV geometric remodeling. We sought to study these characteristics in a group of GHD patients, in an attempt to establish the BMI-independent role of GHD. Methods Fifty-four patients, 28 F and 26 M, aged 45.9 ± 13.1, with adult-onset GHD (pituitary adenomas 48.2%, empty sella 27.8%, pituitary inflammation 5.5%, cranio-pharyngioma 3.7%, not identified pathogenesis 14.8%) were enrolled. To minimize any possible interferences of BMI on the aim of this study, the control group included 20 age- and weight-matched healthy subjects. The LV geometry was identified by the relationship between LVMi (cut-off 125 g/m2) and relative wall thickness (cut-off 0.45) at echocardiography. Results There was no significant between-group difference in resting cardiac morphology and function, nor when considering age-related discrepancy. The majority of patients had normal-low LVM/LVMi, but about one fourth of them showed higher values. These findings correlated to relatively high circulating IGF-1 and systolic blood pressure at rest. The main LV geometric pattern was eccentric hypertrophy in 22% of GHD population (26% of with severe GHD) and in 15% of controls (p = NS). Conclusion Though the lack of significant differences in resting LV morphology and function, about 25% of GHD patients showed high LVMi (consisting of eccentric hypertrophy), not dissimilarly to overweight controls. This finding, which prognostic role is well known in obese and hypertensive patients, is worthy to be investigated in GHD patients through wider controlled trials. PMID:16507109

  11. [EFFICACY OF STANDARD TWO-YEAR COMPREHENSIVE THERAPY TO ACHIEVE TARGET BLOOD PRESSURE AND REGRESSION DEGREES OF REMODELING OF THE LEFT VENTRICULAR HYPERTROPHY IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION WITH COMORBID HYPERTENSION].

    PubMed

    Denesiuk, E V

    2015-01-01

    The study involved 23 men after acute myocardial infarction (AMI) with comorbid arterial hypertension (AH). Mean age of patients was 56.7 years. Recurrent myocardial infarction was determined in 38.4%, cardiac failure I-III functional classes--100% of the cases. All patients underwent clinical examination, electrocardiography and echocardiography, blood lipid profile. Standard comprehensive treatment for two years included an perindopril 5-10 mg/day, beta-blocker bisoprolol--5-10 mg/day, antisclerotic drug atorvastatin--20 mg/day and aspirin--75 mg/day. The patients after treatment was determined by a gradual increase towards the target of AT at 3, 6 and 12 to 24 months. Concentric left ventricular hypertrophy (LVH) before treatment was determined in 47.8%, eccentric--in 52.2% of patients. In the study of degrees of LVH I (initial) the extent to treatment was determined by 4.3%, II (moderate)--26.1%, III (large)--at 69.6%, indicating the development of cardiac remodeling. After the treatment was determined by marked reduction III (large) degree and transfer it in the II (moderate) and I (small) degree of left ventricular hypertrophy due to more or less pronounced changes remodeling left ventricular. The obtained data allow a more detailed and adequately assess the structural and functional outcome variables and determine the regression of myocardial hypertrophy in the background to achieve target blood pressure, which is important in practical cardiology. PMID:27491146

  12. Effect of Microvascular Obstruction and Intramyocardial Hemorrhage by CMR on LV Remodeling and Outcomes After Myocardial Infarction

    PubMed Central

    Hamirani, Yasmin S.; Wong, Andrew; Kramer, Christopher M.; Salerno, Michael

    2015-01-01

    The goal of this systematic analysis is to provide a comprehensive review of the current cardiac magnetic resonance data on microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). Data related to the association of MVO and IMH in patients with acute myocardial infarction (MI) with left ventricular (LV) function, volumes, adverse LV remodeling, and major adverse cardiac events (MACE) were critically analyzed. MVO is associated with a lower ejection fraction, increased ventricular volumes and infarct size, and a greater risk of MACE. Late MVO is shown to be a stronger prognostic marker for MACE and cardiac death, recurrent MI, congestive heart failure/heart failure hospitalization, and follow-up LV end-systolic volumes than early MVO. IMH is associated with LV remodeling and MACE on pooled analysis, but because of limited data and heterogeneity in study methodology, the effects of IMH on remodeling require further investigation. PMID:25212800

  13. An evaluation of potential signals for ventricular arrhythmia and cardiac arrest with dolasetron, ondansetron, and granisetron in the fda combined spontaneous reporting system/adverse event reporting system

    PubMed Central

    Schnell, Frederick M.; Coop, Andrew J.

    2005-01-01

    Background: Of the US Food and Drug Administration (FDA)-approved5-hydroxytryptamine type 3 (5-HT3)-receptor antagonists, dolasetron, ondan-setron, granisetron, and palonosetron, only dolasetron and palonosetron have a precaution in their FDA labeling concerning corrected QT interval (QTc) prolongation. At FDA approved doses, QTc prolongation has been observed in clinical trials with some 5-HT3 receptor antagonists (however, palonosetron has been only recently approved, with few published clinical data available). However, due to patient exclusion criteria, such trials with 5-HT3 receptor antagonists may have failed to examine the risk of these agents in “real world” patients with cancer. Objective: The aim of this analysis was to assess the potential risk for selected cardiac adverse events associated with dolasetron, ondansetron, and granisetron use. Methods: The FDA combined Spontaneous Reporting System/Adverse Event Reporting System database was analyzed. The process of analyzing such a database for early warnings of potential hazards is known as signal generation. The statistical technique proportional reporting ratio (PRR) was used to aid detection of a potential signal within the database. PRR is the observed proportion of a given adverse event for the drug of interest (the number of events of interest for the drug divided by the total number of reports for the drug) divided by the expected proportion. Through the third quarter of 2002, the database was searched using the preferred term electrocardiogram qt corrected interval prolonged. Results: One, 3, and 0 cases were reported for dolasetron, ondansetron, andgranisetron, respectively. The number of cases did not satisfy 1 of the 3 criteria we utilized to define a potential signal, the 3 criteria being: 3 or more reported cases of the adverse event, a PRR value of at least 2, and a χ2 value of >4. As this term may be unlikely to be reported, the database was also searched using the term ventricular

  14. Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction

    PubMed Central

    Zuba-Surma, Ewa K; Guo, Yiru; Taher, Hisham; Sanganalmath, Santosh K; Hunt, Greg; Vincent, Robert J; Kucia, Magda; Abdel-Latif, Ahmed; Tang, Xian-Liang; Ratajczak, Mariusz Z; Dawn, Buddhadeb; Bolli, Roberto

    2011-01-01

    Abstract Adult bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) exhibit a Sca-1+/Lin–/CD45– phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1 × 106) of freshly isolated, non-expanded VSEL-SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Because the frequency of VSEL-SCs in the marrow is very low, we examined whether VSEL-SCs can be expanded in culture without loss of therapeutic efficacy. Mice underwent a 30 min. coronary occlusion followed by reperfusion and, 48 hrs later, received an intramyocardial injection of vehicle (group I, n= 11), 1 × 105 enhanced green fluorescent protein (EGFP)-labelled expanded untreated VSEL-SCs (group II, n= 7), or 1 × 105 EGFP-labelled expanded VSEL-SCs pre-incubated in a cardiogenic medium (group III, n= 8). At 35 days after myocardial infarction (MI), mice treated with pre-incubated VSEL-SCs exhibited better global and regional LV systolic function and less LV hypertrophy compared with vehicle-treated controls. In contrast, transplantation of expanded but untreated VSEL-SCs did not produce appreciable reparative benefits. Scattered EGFP+ cells expressing α-sarcomeric actin, platelet endothelial cell adhesion molecule (PECAM)-1, or von Willebrand factor were present in VSEL-SC-treated mice, but their numbers were very small. No tumour formation was observed. We conclude that VSEL-SCs expanded in culture retain the ability to alleviate LV dysfunction and remodelling after a reperfused MI provided that they are exposed to a combination of cardiomyogenic growth factors and cytokines prior to transplantation. Counter intuitively, the mechanism whereby such pre-incubation confers therapeutic efficacy does not involve differentiation into new cardiac cells. These results

  15. Percutaneous left ventricular restoration.

    PubMed

    Ige, Mobolaji; Al-Kindi, Sadeer G; Attizzani, Guilherme; Costa, Marco; Oliveira, Guilherme H

    2015-04-01

    The ventricular partitioning device known as Parachute is the first and only percutaneously implantable device aimed at restoration of normal left ventricular geometry in humans. Since its conception, this technology has undergone extensive animal and human testing, with proved feasibility and safety, and is currently being studied in a pivotal randomized clinical trial. This article discusses ventricular remodeling and therapies attempted in the past, details the components of the ventricular partitioning device, describes the implanting technique, and reviews the most current experience of this device in humans. PMID:25834974

  16. Estrogen attenuates chronic volume overload induced structural and functional remodeling in male rat hearts

    PubMed Central

    Murray, David B.; Voloshenyuk, Tetyana G.; Brower, Gregory L.; Bradley, Jessica M.; Janicki, Joseph S.

    2010-01-01

    We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload. PMID:19933421

  17. Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial

    PubMed Central

    Tuñón, José; González-Hernández, Ignacio; Llanos-Jiménez, Lucía; Alonso-Martín, Joaquín; Escudier-Villa, Juan M; Tarín, Nieves; Cristóbal, Carmen; Sanz, Petra; Pello, Ana M; Aceña, Álvaro; Carda, Rocío; Orejas, Miguel; Tomás, Marta; Beltrán, Paula; Calero Rueda, Marta; Marcos, Esther; Serrano-Antolín, José María; Gutiérrez-Landaluce, Carlos; Jiménez, Rosa; Cabezudo, Jorge; Curcio, Alejandro; Peces-Barba, Germán; González-Parra, Emilio; Muñoz-Siscart, Raquel; González-Casaus, María Luisa; Lorenzo, Antonio; Huelmos, Ana; Goicolea, Javier; Ibáñez, Borja; Hernández, Gonzalo; Alonso-Pulpón, Luis M; Farré, Jerónimo; Lorenzo, Óscar; Mahíllo-Fernández, Ignacio; Egido, Jesús

    2016-01-01

    Introduction Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. Methods and analysis The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months. Primary objective: to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume ≥10% (MRI). Secondary objectives: change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI. Ethics and dissemination This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of

  18. Effects of liraglutide, a glucagon-like peptide-1 analog, on left ventricular remodeling assessed by cardiac magnetic resonance imaging in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

    PubMed

    Nozue, Tsuyoshi; Yamada, Masayo; Tsunoda, Tetsuji; Katoh, Hiromasa; Ito, Shimpei; Iwaki, Taku; Michishita, Ichiro

    2016-08-01

    The clinical efficacy of glucagon-like peptide-1 (GLP-1) analogs in patients with acute myocardial infarction (AMI) is uncertain. The purpose of the present study was to evaluate the effects of the GLP-1 analog liraglutide on left ventricular (LV) remodeling in patients with AMI. We retrospectively evaluated the effects of liraglutide on LV remodeling assessed by cardiac magnetic resonance imaging (CMRI) in 15 patients with type 2 diabetes who were successfully treated with primary percutaneous coronary intervention (PCI) for AMI. Patients were divided into two groups based on their hypoglycemic medication: liraglutide use (group L; n = 6) or standard therapy (group S; n = 9). The CMRI findings in the early phase and at the 6-month follow-up were compared. At the 6-month follow-up, group S showed increases in LV end-diastolic (from 64 to 74 mL/m(2), p = 0.08) and end-systolic (from 38 to 45 mL/m(2), p = 0.13) volume indexes, whereas no such increase was observed in group L. The LV mass index (LVMI) was significantly smaller in group L than in group S at baseline (64 vs. 75 g/m(2), p = 0.05) and at follow-up (56 vs. 78 g/m(2), p = 0.009). Multivariate regression analysis showed that liraglutide use was an independent negative predictor of LVMI (β = -0.720, p = 0.003). In conclusion, liraglutide may be able to prevent the progression of LV remodeling and is associated with a lower LV mass in diabetic patients with AMI undergoing primary PCI. PMID:26293570

  19. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    PubMed Central

    Zeng, Zhipeng; Yu, Kunwu; Chen, Long; Li, Weihua; Xiao, Hong; Huang, Zhengrong

    2016-01-01

    CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV) function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th) cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically. PMID:27144181

  20. Depression Increases Sympathetic Activity and Exacerbates Myocardial Remodeling after Myocardial Infarction: Evidence from an Animal Experiment

    PubMed Central

    Liu, Tao; Yuan, Xiaoran; Ruan, Bing; Sun, Lifang; Tang, Yanhong; Yang, Bo; Hu, Dan; Huang, Congxin

    2014-01-01

    Depression is an independent risk factor for cardiovascular events and mortality in patients with myocardial infarction (MI). Excessive sympathetic activation and serious myocardial remodeling may contribute to this association. The aim of this study was to discuss the effect of depression on sympathetic activity and myocardial remodeling after MI. Wild-type (WT) rats were divided into a sham group (Sham), a myocardial infarction group (MI), a depression group (D), and a myocardial infarction plus depression group (MI+D). Compared with controls, the MI+D animals displayed depression-like behaviors and attenuated body weight gain. The evaluation of sympathetic activity showed an increased level in plasma concentrations of epinephrine and norepinephrine and higher expression of myocardial tyrosine hydroxylase in the MI+D group than the control groups (p<0.05 for all). Cardiac function and morphologic analyses revealed a decreased fractional shortening accompanied by increased left ventricular dimensions, thinning myocardium wall, and reduced collagen repair in the MI+D group compared with the MI group (p<0.05 for all). Frequent premature ventricular contractions, prolonged QT duration and ventricular repolarization duration, shorted effective refractory period, and increased susceptibility to ventricular arrhythmia were displayed in MI+D rats. These results indicate that sympathetic hyperactivation and exacerbated myocardial remodeling may be a plausible mechanism linking depression to an adverse prognosis after MI. PMID:25036781

  1. [Enalapril reduces the degree of left ventricular remodeling after acute myocardial infarction and reduces the incidence of arrhythmia in ischemic disease].

    PubMed

    Altieri, P I; González, R; de Mello, W; Escobales, N

    1994-12-01

    The present study shows that enalapril prevents the excessive remodeling of the left ventricle after acute myocardial infarction. This randomized and double blind clinical study analysed 50 patients with an inferior myocardial infarction. The effect of enalapril was evaluated through cardiac volumes, ejection fraction, neurohormonal levels and incidence of the left ventricle disfunction after acute myocardial infarction. The patients treated with enalapril showed a significant reduction on the values of nor-epinefrine, angiotensine II, natriuretic hormone and vasopressine, four weeks after initiation of treatment. The ejection fraction and the level of the wall movement was more favourable, four weeks after infarction, in the group treated with enalapril. The incidence of congestive heart failure and arrhythmias was lower in the group treated with enalapril. So, we conclude that enalapril is a drug that prevents the excessive remodelling of the left ventricle after an acute myocardial infarction. PMID:7873221

  2. The response of the pulmonary circulation and right ventricle to exercise: exercise-induced right ventricular dysfunction and structural remodeling in endurance athletes (2013 Grover Conference series)

    PubMed Central

    Roberts, Timothy; Claessen, Guido

    2014-01-01

    Abstract There is unequivocal evidence that exercise results in considerable health benefits. These are the result of positive hormonal, metabolic, neuronal, and structural changes brought about by the intermittent physiological challenge of exercise. However, there is evolving evidence that intense exercise may place disproportionate physiological stress on the right ventricle (RV) and the pulmonary circulation. Both echocardiographic and invasive studies are consistent in demonstrating that pulmonary arterial pressures increase progressively with exercise intensity, such that the harder one exercises, the greater the load on the RV. This disproportionate load can result in fatigue or damage of the RV if the intensity and duration of exercise is sufficiently prolonged. This is distinctly different from the load imposed by exercise on the left ventricle (LV), which is moderated by a greater capacity for reductions in systemic afterload. Finally, given the increasing RV demand during exercise, it may be hypothesized that chronic exercise–induced cardiac remodeling (the so-called athlete’s heart) may also disproportionately affect the RV. Indeed, there is evidence, although somewhat inconsistent, that RV volume increases may be relatively greater than those for the LV. Perhaps more importantly, there is a suggestion that chronic endurance exercise may cause electrical remodeling, predisposing some athletes to serious arrhythmias originating from the RV. Thus, a relatively consistent picture is emerging of acute stress, prolonged fatigue, and long-term remodeling, which all disproportionately affect the RV. Thus, we contend that the RV should be considered a potential Achilles’ heel of the exercising heart. PMID:25621154

  3. The response of the pulmonary circulation and right ventricle to exercise: exercise-induced right ventricular dysfunction and structural remodeling in endurance athletes (2013 Grover Conference series).

    PubMed

    La Gerche, André; Roberts, Timothy; Claessen, Guido

    2014-09-01

    There is unequivocal evidence that exercise results in considerable health benefits. These are the result of positive hormonal, metabolic, neuronal, and structural changes brought about by the intermittent physiological challenge of exercise. However, there is evolving evidence that intense exercise may place disproportionate physiological stress on the right ventricle (RV) and the pulmonary circulation. Both echocardiographic and invasive studies are consistent in demonstrating that pulmonary arterial pressures increase progressively with exercise intensity, such that the harder one exercises, the greater the load on the RV. This disproportionate load can result in fatigue or damage of the RV if the intensity and duration of exercise is sufficiently prolonged. This is distinctly different from the load imposed by exercise on the left ventricle (LV), which is moderated by a greater capacity for reductions in systemic afterload. Finally, given the increasing RV demand during exercise, it may be hypothesized that chronic exercise-induced cardiac remodeling (the so-called athlete's heart) may also disproportionately affect the RV. Indeed, there is evidence, although somewhat inconsistent, that RV volume increases may be relatively greater than those for the LV. Perhaps more importantly, there is a suggestion that chronic endurance exercise may cause electrical remodeling, predisposing some athletes to serious arrhythmias originating from the RV. Thus, a relatively consistent picture is emerging of acute stress, prolonged fatigue, and long-term remodeling, which all disproportionately affect the RV. Thus, we contend that the RV should be considered a potential Achilles' heel of the exercising heart. PMID:25621154

  4. Arrhythmogenic right ventricular cardiomyopathy/dysplasia.

    PubMed

    Thiene, Gaetano; Corrado, Domenico; Basso, Cristina

    2007-01-01

    Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias. Its prevalence has been estimated to vary from 1:2,500 to 1:5,000. ARVC/D is a major cause of sudden death in the young and athletes. The pathology consists of a genetically determined dystrophy of the right ventricular myocardium with fibro-fatty replacement to such an extent that it leads to right ventricular aneurysms. The clinical picture may include: a subclinical phase without symptoms and with ventricular fibrillation being the first presentation; an electrical disorder with palpitations and syncope, due to tachyarrhythmias of right ventricular origin; right ventricular or biventricular pump failure, so severe as to require transplantation. The causative genes encode proteins of mechanical cell junctions (plakoglobin, plakophilin, desmoglein, desmocollin, desmoplakin) and account for intercalated disk remodeling. Familiar occurrence with an autosomal dominant pattern of inheritance and variable penetrance has been proven. Recessive variants associated with palmoplantar keratoderma and woolly hair have been also reported. Clinical diagnosis may be achieved by demonstrating functional and structural alterations of the right ventricle, depolarization and repolarization abnormalities, arrhythmias with the left bundle branch block morphology and fibro-fatty replacement through endomyocardial biopsy. Two dimensional echo, angiography and magnetic resonance are the imaging tools for visualizing structural-functional abnormalities. Electroanatomic mapping is able to detect areas of low voltage corresponding to myocardial atrophy with fibro-fatty replacement. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, dialted cardiomyopathy and sarcoidosis. Only palliative therapy is available and consists of antiarrhythmic drugs, catheter ablation and

  5. Age, Gender and Load-Related Influences on Left Ventricular Geometric Remodeling, Systolic Mid-Wall Function, and NT-ProBNP in Asymptomatic Asian Population

    PubMed Central

    Chen, Chi; Sung, Kuo-Tzu; Shih, Shou-Chuan; Liu, Chuan-Chuan; Kuo, Jen-Yuan; Hou, Charles Jia-Yin; Hung, Chung-Lieh; Yeh, Hung-I

    2016-01-01

    Background Advanced age is associated with left ventricle (LV) remodeling and impaired cardiac function that may increase the risk of heart failure. Even so, studies regarding age-related cardiac remodeling in a large, asymptomatic Asian population remain limited. Materials and Methods We studied 8,410 asymptomatic participants (49.7 ±11.7 y, 38.9% women) in a health evaluation cohort (2004–2012) at a tertiary center in Northern Taiwan. We analyzed age-related alterations for all echocardiography-derived cardiac structures/functions and the associations with circulating N-terminal prohormone of brain natriuretic peptide (NT-proBNP). We also explored sex-related differences in these measures. Results In our cohort of 8,410 participants, advanced age was associated with greater LV wall thickness, larger LV total mass (+5.08 g/decade), and greater LV mass index (4.41 g/m2/decade), as well as increased serum NT-proBNP level (+18.89 pg/mL/decade). An accompanying reduction of stress-corrected midwall fractional shortening (–0.1%/decade) with aging was apparent in women after multi-variate adjustment (–0.09%/decade, p = 0.001). Furthermore, women demonstrated greater overall increase in LV wall thickness, LV mass index, and NT-proBNP compared to men (p for interaction: <0.001). All blood pressure components, including systolic, diastolic, and pulse pressures were independently associated with greater wall thickness and LV mass index after adjustment for confounders (all p <0.001). The associations between age and cardiac remodeling or mid-wall functions were further confirmed in a subset of study subjects with repeated follow up by GEE model. Conclusions Significant associations of unfavorable LV remodeling and advanced age in our asymptomatic Asian population were observed, along with sex differences. These data may help explain the incidence of some diverse gender-related cardiovascular diseases, especially heart failure. PMID:27280886

  6. Left ventricular restoration devices.

    PubMed

    Oliveira, Guilherme H; Al-Kindi, Sadeer G; Bezerra, Hiram G; Costa, Marco A

    2014-04-01

    Left ventricular (LV) remodeling results in continuous cardiac chamber enlargement and contractile dysfunction, perpetuating the syndrome of heart failure. With current exhaustion of the neurohormonal medical paradigm, surgical and device-based therapies have been increasingly investigated as a way to restore LV chamber architecture and function. Left ventricular restoration has been attempted with surgical procedures, such as partial left ventriculectomy, surgical ventricular restoration with or without revascularization, and devices, such as the Acorn CorCap, the Paracor HeartNet, and the Myocor Myosplint. Whereas all these techniques require surgical access, with or without cardiopulmonary bypass, a newer ventricular partitioning device (VPD) called Parachute, can be delivered percutaneously through the aortic valve. Designed to achieve LV restoration from within the ventricle, this VPD partitions the LV by isolating aneurysmal from normal myocardium thereby diminishing the functioning cavity. This review aims to critically appraise the above methods, with particular attention to device-based therapies. PMID:24574107

  7. Stromal Cell-Derived Factor-1α Activation of Tissue Engineered Endothelial Progenitor Cell Matrix Enhances Ventricular Function after Myocardial Infarction by Inducing Neovasculogenesis

    PubMed Central

    Frederick, John R.; Fitzpatrick, J. Raymond; McCormick, Ryan C.; Harris, David A.; Kim, Ah-Young; Muenzer, Jeffrey R.; Marotta, Nicole; Smith, Maximilian J.; Cohen, Jeffrey E.; Hiesinger, William; Atluri, Pavan; Woo, Y. Joseph

    2014-01-01

    Background Myocardial ischemia causes cardiomyocyte death, adverse ventricular remodeling, and ventricular dysfunction. Endothelial progenitor cells (EPC) have been shown to ameliorate this process, particularly when activated with stromal cell-derived factor-1α (SDF). We hypothesized that implantation of a tissue engineered extracellular matrix scaffold seeded with EPCs primed with SDF could induce neovasculogenesis, prevent adverse remodeling, and preserve ventricular function after myocardial infarction (MI). Methods and Results Lewis rats (n=82) underwent left anterior descending artery ligation to induce MI. EPCs were cultured on a vitronectin/collagen scaffold, and primed with SDF to generate the activated EPC matrix (EPCM). EPCM was sutured to the anterolateral left ventricular (LV) wall including the region of ischemia.. At four weeks, when compared to controls, borderzone myocardial tissue demonstrated increased levels of VEGF in the EPCM group. Vessel density as assessed by immunohistochemical microscopy was significantly increased in the EPCM group (4.1 vs 6.2 vessels/high-powered field, p<0.001), and microvascular perfusion measured by lectin microangiography was enhanced four-fold (0.7 vs. 2.7% vessel volume/section volume, p=0.04). Ventricular geometry and scar fraction assessed by analysis of sectioned hearts exhibited significantly preserved LV internal diameter (9.7mm vs. 8.6mm, p=0.005) and decreased infarct scar expressed as percent of total section area (16% vs. 7%, p=0.002) when compared to all other groups. In addition, EPCM animals showed a significant preservation of function as measured by echocardiography, pressure volume-conductance, and Doppler flow. Conclusions Extracellular matrix seeded with EPCs primed with SDF induces borderzone neovasculogenesis, attenuates adverse ventricular remodeling, and preserves ventricular function after MI. PMID:20837901

  8. Transplantation of Bone Marrow-Derived Very Small Embryonic-Like Stem Cells Attenuates Left Ventricular Dysfunction and Remodeling After Myocardial Infarction

    PubMed Central

    Dawn, Buddhadeb; Tiwari, Sumit; Kucia, Magdalena J.; Zuba-Surma, Ewa K.; Guo, Yiru; SanganalMath, Santosh K.; Abdel-Latif, Ahmed; Hunt, Greg; Vincent, Robert J.; Taher, Hisham; Reed, Nathan J.; Ratajczak, Mariusz Z.; Bolli, Roberto

    2013-01-01

    Adult bone marrow (BM) contains Sca-1+/Lin−/CD45− very small embryonic-like stem cells (VSELs) that express markers of several lineages, including cardiac markers, and differentiate into cardiomyocytes in vitro. We examined whether BM-derived VSELs promote myocardial repair after a reperfused myocardial infarction (MI). Mice underwent a 30-minute coronary occlusion followed by reperfusion and received intramyocardial injection of vehicle (n = 11), 1 × 105 Sca-1+/Lin−/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n = 13 [cell control group]), or 1 × 104 Sca-1+/Lin−/CD45− EGFP-labeled cells (n = 14 [VSEL-treated group]) at 48 hours after MI. At 35 days after MI, VSEL-treated mice exhibited improved global and regional left ventricular (LV) systolic function (echocardiography) and attenuated myocyte hypertrophy in surviving tissue (histology and echocardiography) compared with vehicle-treated controls. In contrast, transplantation of Sca-1+/Lin−/CD45+ cells failed to confer any functional or structural benefits. Scattered EGFP+ myocytes and capillaries were present in the infarct region in VSEL-treated mice, but their numbers were very small. These results indicate that transplantation of a relatively small number of CD45− VSELs is sufficient to improve LV function and alleviate myocyte hypertrophy after MI, supporting the potential therapeutic utility of these cells for cardiac repair. PMID:18420834

  9. Prenatal programming: adverse cardiac programming by gestational testosterone excess.

    PubMed

    Vyas, Arpita K; Hoang, Vanessa; Padmanabhan, Vasantha; Gilbreath, Ebony; Mietelka, Kristy A

    2016-01-01

    Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30-90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells -c3 (NFATc3), and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. PMID:27328820

  10. Prenatal programming: adverse cardiac programming by gestational testosterone excess

    PubMed Central

    Vyas, Arpita K.; Hoang, Vanessa; Padmanabhan, Vasantha; Gilbreath, Ebony; Mietelka, Kristy A.

    2016-01-01

    Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30–90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells –c3 (NFATc3), and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. PMID:27328820

  11. Cardiac ventricular aneurysm

    PubMed Central

    Harley, Hugh R. S.

    1969-01-01

    A case of successful excision of a ventricular aneurysm due to myocardial infarction is presented. The aetiology, incidence, pathogenesis, pathology, clinical features, and diagnosis of the condition are discussed. An account is given of the haemodynamic upset caused by aneurysms of the ventricle. The prognosis of untreated aneurysms is discussed. Although there is difference of opinion, it is concluded that a ventricular aneurysm adversely affects the prognosis after myocardial infarction. The indications for, and the mortality and results of, resection of ventricular aneurysms are discussed. The conclusion is drawn that persistent cardiac failure and angina can be relieved and the risk of systemic embolism reduced by the excision of expansile ventricular aneurysms of a fibrous nature. It is possible that excision may also reduce the incidence of subsequent acute myocardial infarction. Images PMID:5821618

  12. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

    PubMed

    Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions. PMID:26660322

  13. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation

    PubMed Central

    Bernardo, Bianca C.; Sapra, Geeta; Patterson, Natalie L.; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A.; McMullen, Julie R.

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions. PMID:26660322

  14. Role of reactive oxygen species in myocardial remodeling.

    PubMed

    Zhang, Min; Shah, Ajay M

    2007-03-01

    Adverse cardiac remodeling is a fundamental process in the progression to chronic heart failure. Although the mechanisms underlying cardiac remodeling are multi-factorial, a significant body of evidence points to the crucial roles of increased reactive oxygen species. This article reviews recent advances in delineating the different sources of production for reactive oxygen species (namely mitochondria, xanthine oxidase, uncoupled nitric oxide synthases, and NADPH oxidases) that may be involved in cardiac remodeling and the aspects of the remodeling process that they affect. These data could suggest new ways of targeting redox pathways for the prevention and treatment of adverse cardiac remodeling. PMID:17386182

  15. STIM1-dependent Ca2+ microdomains are required for myofilament remodeling and signaling in the heart

    PubMed Central

    Parks, Cory; Alam, Mohammad Afaque; Sullivan, Ryan; Mancarella, Salvatore

    2016-01-01

    In non-excitable cells stromal interaction molecule 1 (STIM1) is a key element in the generation of Ca2+ signals that lead to gene expression, migration and cell proliferation. A growing body of literature suggests that STIM1 plays a key role in the development of pathological cardiac hypertrophy. However, the precise mechanisms involving STIM-dependent Ca2+ signaling in the heart are not clearly established. Here, we have investigated the STIM1-associated Ca2+ signals in cardiomyocytes and their relevance to pathological cardiac remodeling. We show that mice with inducible, cardiac-restricted, ablation of STIM1 exhibited left ventricular reduced contractility, which was corroborated by impaired single cell contractility. The spatial properties of STIM1-dependent Ca2+ signals determine restricted Ca2+ microdomains that regulate myofilament remodeling and activate spatially segregated pro-hypertrophic factors. Indeed, mice lacking STIM1 showed less adverse structural remodeling in response to pressure overload-induced cardiac hypertrophy. These results highlight how STIM1-dependent Ca2+ microdomains have a major impact on intracellular Ca2+ homeostasis, cytoskeletal remodeling and cellular signaling, even when excitation-contraction coupling is present. PMID:27150728

  16. Pay attention to cardiac remodeling in cancer cachexia.

    PubMed

    Zheng, Yawen; Chen, Han; Li, Xiaoqing; Sun, Yuping

    2016-07-01

    Cancer cachexia is a complex and multifaceted disease state characterized by fatigue, weakness, and loss of skeletal muscle and adipose tissue. Recently, the profound negative effects of cancer cachexia on cardiac tissue draw much attention, which is likely to contribute to mortality in tumor-bearing animals. The mechanism of cardiac remodeling is not so clear and involved with a series of molecular alterations. In cancer cachexia model, progressive loss of left ventricular mass and decrease in myocardial function is observed and cardiac autonomic functions are altered. Levels of several emerging cardiovascular neurohormones are found elevating in patients with cancer, but it is still controversial whether the changes could reflect the heart injury accurately. The remedy for cardiac remodeling has been explored. It is showed that exercise can modulate signaling pathways activated by wasting cytokines and impact on the resulting outcomes on heart adaptation. Some drugs, such as bisoprolol, spironolactone, perindopril, tandospirone, and simvastatin, can mitigate adverse effects of the tumor on the heart and prolong survival. PMID:27108265

  17. Rho Kinases and Cardiac Remodeling.

    PubMed

    Shimizu, Toru; Liao, James K

    2016-06-24

    Hypertensive cardiac remodeling is characterized by left ventricular hypertrophy and interstitial fibrosis, which can lead to heart failure with preserved ejection fraction. The Rho-associated coiled-coil containing kinases (ROCKs) are members of the serine/threonine protein kinase family, which mediates the downstream effects of the small GTP-binding protein RhoA. There are 2 isoforms: ROCK1 and ROCK2. They have different functions in different types of cells and tissues. There is growing evidence that ROCKs contribute to the development of cardiovascular diseases, including cardiac fibrosis, hypertrophy, and subsequent heart failure. Recent experimental studies using ROCK inhibitors, such as fasudil, have shown the benefits of ROCK inhibition in cardiac remodeling. Mice lacking each ROCK isoform also exhibit reduced myocardial fibrosis in a variety of pathological models of cardiac remodeling. Indeed, clinical studies with fasudil have suggested that ROCKs could be potential novel therapeutic targets for cardiovascular diseases. In this review, we summarize the current understanding of the roles of ROCKs in the development of cardiac fibrosis and hypertrophy and discuss their therapeutic potential for deleterious cardiac remodeling. (Circ J 2016; 80: 1491-1498). PMID:27251065

  18. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice.

    PubMed

    Duerr, Georg D; Dewald, Daniela; Schmitz, Eva J; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT(-/-))-mice (n = 8-10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT(-/-)-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2(-/-)-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT(-/-)-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2(-/-)-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  19. Tissue Inhibitor of Metalloproteinase-2 Gene Delivery Ameliorates Post-Infarction Cardiac Remodeling

    PubMed Central

    Ramani, Ravi; Nilles, Kathleen; Gibson, Gregory; Burkhead, Benjamin; Mathier, Michael; McNamara, Dennis; McTiernan, Charles F.

    2011-01-01

    Hypothesis Adenoviral-mediated (AdV-T2) overexpression of TIMP-2 would blunt ventricular remodeling and improve survival in a murine model of chronic ischemic injury. Methods Male mice (n=124) aged 10–14 weeks underwent either 1) left coronary artery ligation to induce myocardial infarction (MI group, n=36), 2) myocardial injection of 6×1010 viral particles of AdV-T2 immediately post-MI (MI+T2 group, n=30), 3) myocardial injection of 6×1010 viral particles of a control adenovirus (MI+Ct, n=38), or 4) received no intervention (controls, n=20). On post-MI day 7, surviving mice (n=79) underwent echocardiographic, immunohistochemical and biochemical analysis. Results In infarcted animals, the MI+T2 group demonstrated improved survival (p< 0.02), better preservation of developed pressure and ventricular diameter (p<0.04), and the lowest expression and activity of MMP-2 and MMP-9 (P<0.04) compared with MI and MI+Ct groups.. All infarcted hearts displayed significantly increased inflammatory cell infiltration (p<0.04 versus control, MI, or MI+T2), with infiltration highest in the MI+Ct group and lowest in the MI+T2 group (p<0.04). Conclusions Adenoviral mediated myocardial delivery of the TIMP-2 gene improves post-MI survival and limits adverse remodeling in a murine model of myocardial infarction. PMID:21348952

  20. A randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of intracoronary application of a novel bioabsorbable cardiac matrix for the prevention of ventricular remodeling after large ST-segment elevation myocardial infarction: Rationale and design of the PRESERVATION I trial.

    PubMed

    Rao, Sunil V; Zeymer, Uwe; Douglas, Pamela S; Al-Khalidi, Hussein; Liu, Jingyu; Gibson, C Michael; Harrison, Robert W; Joseph, Diane S; Heyrman, Reinilde; Krucoff, Mitchell W

    2015-11-01

    Postinfarction left ventricular (LV) remodeling can result in chronic heart failure and functional impairment. Although pharmacological strategies for established heart failure can be beneficial, preventing remodeling remains a challenge. Injectable bioabsorbable alginate or "bioabsorbable cardiac matrix" (BCM), composed of an aqueous mixture of sodium alginate and calcium gluconate, is a sterile colorless liquid that is a polysaccharide polymer produced from brown seaweed. When exposed to excess ionized calcium present in infarcted myocardium, BCM assembles to form a flexible gel, structurally resembling extracellular matrix, which provides temporary structural support to the infarct zone through and beyond the time needed for mature fibrotic tissue to develop. The PRESERVATION I trial is an early phase randomized, double-blind, placebo-controlled trial comparing intracoronary application of 4 mL of BCM with saline control in patients who develop large infarctions after successful reperfusion of large ST-segment elevation myocardial infarction (MI). Subjects will be randomized 2:1 to either BCM or saline control and will have the study device deployed through an intracoronary microcatheter in the infarct-related artery 2 to 5 days after index ST-segment elevation MI treated with successful primary or rescue percutaneous coronary intervention. The primary effectiveness end point is the absolute change in LV diastolic volume index as measured by 3-dimensional echocardiography from baseline to 6 months after BCM deployment. Secondary effectiveness end points include clinical outcomes, patient-reported quality of life, additional echocardiographic measures, and functional status measures. In summary, the PRESERVATION I trial is a randomized double-blind trial evaluating the effectiveness and safety of the novel device BCM in preventing LV remodeling patients who have large MIs despite undergoing successful primary or rescue percutaneous coronary intervention. PMID

  1. Ventricular tachycardia

    MedlinePlus

    ... of implanting a device called an implantable cardioverter defibrillator (ICD). The ICD is most often implanted in ... tachycardia; V tach; Tachycardia - ventricular Images Implantable cardioverter-defibrillator References Olgin JE, Zipes DP. Specific Arrhythmias: Diagnosis ...

  2. Ventricular fibrillation

    MedlinePlus

    ... Fibrillation is an uncontrolled twitching or quivering of muscle fibers (fibrils). When it occurs in the lower chambers of the heart, it is called ventricular fibrillation. During ... the heart muscle does not get enough oxygen for any reason. ...

  3. Pyrvinium, a Potent Small Molecule Wnt Inhibitor, Promotes Wound Repair and Post-MI Cardiac Remodeling

    PubMed Central

    Saraswati, Sarika; Alfaro, Maria P.; Thorne, Curtis A.; Atkinson, James; Lee, Ethan; Young, Pampee P.

    2010-01-01

    Wnt signaling plays an important role in developmental and stem cell biology. To test the hypothesis that temporary inhibition of Wnt signaling will enhance granulation tissue and promote angiogenesis in tissue repair, we employed a recently characterized small molecule Wnt inhibitor. Pyrvinium is an FDA-approved drug that we identified as a Wnt inhibitor in a chemical screen for small molecules that stabilize β-catenin and inhibit Axin degradation. Our subsequent characterization of pyrvinium has revealed that its critical cellular target in the Wnt pathway is Casein Kinase 1α. Daily administration of pyrvinium directly into polyvinyl alcohol (PVA) sponges implanted subcutaneously in mice generated better organized and vascularized granulation tissue; this compound also increased the proliferative index of the tissue within the sponges. To evaluate its effect in myocardial repair, we induced a myocardial infarction (MI) by coronary artery ligation and administered a single intramyocardial dose of pyrvinium. Mice were evaluated by echocardiography at 7 and 30 days post-MI and treatment; post mortem hearts were evaluated by histology at 30 days. Pyrvinium reduced adverse cardiac remodeling demonstrated by decreased left ventricular internal diameter in diastole (LVIDD) as compared to a control compound. Increased Ki-67+ cells were observed in peri-infarct and distal myocardium of pyrvinium-treated animals. These results need to be further followed-up to determine if therapeutic inhibition of canonical Wnt may avert adverse remodeling after ischemic injury and its impact on myocardial repair and regeneration. PMID:21170416

  4. [THE EFFECTIVENESS OF THE CORRECTION OF ENDOTHELIAL DYSFUNCTION AND REMODELING OF THE BRACHIAL ARTERY WITH CONCENTRIC AND ECCENTRIC LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH UNSTABLE ANGINA WITH COMORBID HYPERTENSION].

    PubMed

    Denesiuk, E V

    2015-01-01

    The study involved patients with unstable angina (UA), comorbid hypertension (AH), myocardial infarction in 55.5% of cases. Systolic blood pressure was (163.2 ± 1.5) mm Hg. Art., diastolic blood pressure--(101.10 ± 0.67) mm Hg. Art., pulse pressure--(61.1 ± 17.0) mm Hg. Art. Examined patients underwent clinical studies, ECG in 12 conventional leads, echocardiography in M and B modes, Doppler ultrasonography of the brachial artery. To correct the detected change using standard combined therapy: perindopril 5-10 mg/day, bisoprolol--5-10 mg/day, atorvastatin--20 mg/day, acetylsalicylic acid--75-100 mg/day. Monitoring the treatment was carried out at 3; 6 and 12 months. Standard one-year comprehensive treatment of patients with UA with comorbid AH resulted in significant improvement of effective endothelial dysfunction in concentric and eccentric left ventricular hypertrophy in 3; 6 and 12 months, however, regression of hypertrophy brachial artery advancing much less mainly in concentric left ventricular hypertrophy. PMID:27089719

  5. Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment

    PubMed Central

    Azevedo, Paula S.; Polegato, Bertha F.; Minicucci, Marcos F.; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2016-01-01

    Cardiac remodeling is defined as a group of molecular, cellular and interstitial changes that manifest clinically as changes in size, mass, geometry and function of the heart after injury. The process results in poor prognosis because of its association with ventricular dysfunction and malignant arrhythmias. Here, we discuss the concepts and clinical implications of cardiac remodeling, and the pathophysiological role of different factors, including cell death, energy metabolism, oxidative stress, inflammation, collagen, contractile proteins, calcium transport, geometry and neurohormonal activation. Finally, the article describes the pharmacological treatment of cardiac remodeling, which can be divided into three different stages of strategies: consolidated, promising and potential strategies. PMID:26647721

  6. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  7. Bone Marrow-Derived Multipotent Stromal Cells Promote Myocardial Fibrosis and Reverse Remodeling of the Left Ventricle

    PubMed Central

    Fatkhudinov, Timur; Bolshakova, Galina; Arutyunyan, Irina; Elchaninov, Andrey; Makarov, Andrey; Kananykhina, Evgeniya; Khokhlova, Oksana; Murashev, Arkady; Glinkina, Valeria; Goldshtein, Dmitry; Sukhikh, Gennady

    2015-01-01

    Cell therapy is increasingly recognized as a beneficial practice in various cardiac conditions, but its fundamentals remain largely unclear. The fates of transplanted multipotent stromal cells in postinfarction cardiac microenvironments are particularly understudied. To address this issue, labeled multipotent stromal cells were infused into rat myocardium at day 30 after myocardial infarction, against the background of postinfarction cardiosclerosis. Therapeutic effects of the transplantation were assessed by an exercise tolerance test. Histological examination at 14 or 30 days after the transplantation was conducted by means of immunostaining and quantitative image analysis. An improvement in the functional status of the cardiovascular system was observed after both the autologous and the allogeneic transplantations. Location of the label-positive cells within the heart was restricted to the affected part of myocardium. The transplanted cells could give rise to fibroblasts or myofibroblasts but not to cardiac myocytes or blood vessel cells. Both types of transplantation positively influenced scarring processes, and no expansion of fibrosis to border myocardium was observed. Left ventricular wall thickening associated with reduced dilatation index was promoted by transplantation of the autologous cells. According to the results, multipotent stromal cell transplantation prevents adverse remodeling and stimulates left ventricular reverse remodeling. PMID:25685158

  8. Effect of Neurohormonal Blockade Drug Therapy on Outcomes and Left Ventricular Function and Structure After Left Ventricular Assist Device Implantation.

    PubMed

    Grupper, Avishay; Zhao, Yanjun M; Sajgalik, Pavol; Joyce, Lyle D; Park, Soon J; Pereira, Naveen L; Stulak, John M; Burnett, John C; Edwards, Brooks S; Daly, Richard C; Kushwaha, Sudhir S; Schirger, John A

    2016-06-01

    Neurohormonal blockade drug therapy (NHBDT) is the cornerstone therapy in heart failure (HF) management for promoting reverse cardiac remodeling and improving outcomes. It's utility in left ventricular assist device (LVAD) supported patients remains undefined. Sixty-four patients who received continuous flow LVAD at our institution were retrospectively reviewed and divided into 2 groups: no-NHBDT group (n = 33) received LVAD support only and NHBDT group (n = 31) received concurrent NHBDT based on the clinical judgment of the attending physicians. Cardiac remodeling (echocardiographic parameters and biomarkers) and clinical outcome (functional status, HF-related hospital readmissions, and mortality) data were collected. A statistically significant increase in ejection fraction, decrease in LV end-diastolic diameter index and LV mass index, and a sustained reduction in N-terminal pro B-type natriuretic peptide (NTproBNP) were observed in the NHBDT group at 6 months after LVAD implant (p <0.05). NHBDT-treated patients experienced significantly greater improvement in New York Heart Association functional classification and 6-minute-walk distance throughout the study. The combined end point of cardiovascular death or HF hospitalization was significantly reduced in patients receiving NHBDT (p = 0.013) associated primarily with a 12.1% absolute reduction in HF-related hospitalizations (p = 0.046). In conclusion, NHBDT in LVAD-supported patients is associated with a significant reversal in adverse cardiac remodeling and a reduction in morbidity and mortality compared with LVAD support alone. PMID:27079215

  9. Surgical considerations for the explantation of the Parachute left ventricular partitioning device and the implantation of the HeartMate II left ventricular assist device

    PubMed Central

    Bansal, Shelley; Rosas, Paola C.; Mazzaferri, Ernest L.; Sai-Sudhakar, Chittoor B.

    2016-01-01

    Chronic heart failure is the leading cause of death in the world. With newer therapies, the burden of this disease has decreased; however, a significant number of patients remain refractive to existing therapies. Myocardial infarction often leads to ventricular remodeling and eventually contributes to heart failure. The Parachute™ (Cardiokinetix, Menlo Park, CA) is the first device designed for percutaneous ventricular restoration therapy, which reduces left ventricular volume and minimizes the risk of open surgical procedures. For the first time, we report a case of explantation of the Parachute ventricular partitioning device and transition to a HeartMate II™ left ventricular assist device and the surgical considerations for a successful outcome. PMID:27034560

  10. Surgical considerations for the explantation of the Parachute left ventricular partitioning device and the implantation of the HeartMate II left ventricular assist device.

    PubMed

    Ravi, Yazhini; Bansal, Shelley; Rosas, Paola C; Mazzaferri, Ernest L; Sai-Sudhakar, Chittoor B

    2016-04-01

    Chronic heart failure is the leading cause of death in the world. With newer therapies, the burden of this disease has decreased; however, a significant number of patients remain refractive to existing therapies. Myocardial infarction often leads to ventricular remodeling and eventually contributes to heart failure. The Parachute™ (Cardiokinetix, Menlo Park, CA) is the first device designed for percutaneous ventricular restoration therapy, which reduces left ventricular volume and minimizes the risk of open surgical procedures. For the first time, we report a case of explantation of the Parachute ventricular partitioning device and transition to a HeartMate II™ left ventricular assist device and the surgical considerations for a successful outcome. PMID:27034560

  11. Myocardial repair/remodelling following infarction: roles of local factors

    PubMed Central

    Sun, Yao

    2009-01-01

    Heart failure is a global health problem, appearing most commonly in patients with previous myocardial infarction (MI). Cardiac remodelling, particularly fibrosis, seen in both the infarcted and non-infarcted myocardium is recognized to be a major determinant of the development of impaired ventricular function, leading to a poor prognosis. Elucidating cellular and molecular mechanisms responsible for the accumulation of extracellular matrix is essential for designing cardioprotective and reparative strategies that could regress fibrosis after infarction. Multiple factors contribute to left ventricular remodelling at different stages post-MI. This review will discuss the role of oxidative stress and locally produced angiotensin II in the pathogenesis of myocardial repair/remodelling after MI. PMID:19050008

  12. Pathological Left Ventricular Hypertrophy and Stem Cells: Current Evidence and New Perspectives

    PubMed Central

    Marketou, Maria E.; Parthenakis, Fragiskos; Vardas, Panos E.

    2016-01-01

    Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes. It is the result of complex mechanisms that include not only an increase in protein synthesis and cell size but also proliferating cardiac progenitor cells and the influx of bone marrow-derived cells developing into cardiomyocytes. Stem and progenitor cells are known to contribute to the renewal of adult mammalian cardiomyocytes in case of myocardial injury or pressure and volume overload. They are activated in LVH and play a regulatory role in myocardial repair. They have high proliferative potential and secrete numerous cytokines, growth factors, and microRNAs that play important roles in cell differentiation, cardiac remodeling, and neovascularization. They are mobilized in response to either mechanical or chemical stimuli, hormones, or pharmacologic agents. Another important source of progenitor cells is the epicardial layer. It appears that precursor cells migrate from the epicardium to the myocardium in order to interact with myocardial cells. In addition, migratory cells participate in the formation of almost all cardiac structures in myocardial hypertrophy. Although the pathophysiological mechanisms are still obscure and further studies are required, their properties may open the door to regenerative cell therapy for the prevention of adverse remodeling. PMID:26798360

  13. PARP inhibition and postinfarction myocardial remodeling.

    PubMed

    Halmosi, Robert; Deres, Laszlo; Gal, Roland; Eros, Krisztian; Sumegi, Balazs; Toth, Kalman

    2016-08-01

    Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt-1/GSK-3β, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling. PMID:27392900

  14. Arrhythmogenic Right Ventricular Dysplasia

    MedlinePlus

    MENU Return to Web version Arrhythmogenic Right Ventricular Dysplasia Overview What is arrhythmogenic right ventricular dysplasia? Arrhythmogenic right ventricular dysplasia (say: “uh-rith-mo-jen-ic right ven-trick- ...

  15. Left Ventricular Relative Wall Thickness Versus Left Ventricular Mass Index in Non-Cardioembolic Stroke Patients

    PubMed Central

    Hashem, M-Sherif; Kalashyan, Hayrapet; Choy, Jonathan; Chiew, Soon K.; Shawki, Abdel-Hakim; Dawood, Ahmed H.; Becher, Harald

    2015-01-01

    Abstract In non-cardioembolic stroke patients, the cardiac manifestations of high blood pressure are of particular interest. Emerging data suggest that echocardiographically determined left ventricular hypertrophy is independently associated with risk of ischemic stroke. The primary objective of this study was to evaluate the frequency of different patterns of left ventricular (LV) remodeling and hypertrophy in a group of consecutive patients admitted with non-cardioembolic stroke or transient ischemic attack (TIA). In particular, we were interested in how often the relative wall thickness (RWT) was abnormal in patients with normal LV mass index (LVMI). As both abnormal RWT and LVMI indicate altered LV remodeling, the secondary objective of this research was to study whether a significant number of patients would be missing the diagnosis of LV remodeling if the RWT is not measured. All patients were referred within 48 hours after a stroke or a TIA for a clinically indicated transthoracic echocardiogram. The echocardiographic findings of consecutive patients with non-cardioembolic stroke or TIA were analyzed. All necessary measurements were performed in 368 patients, who were enrolled in the study. Mean age was 63.7 ± 12.5 years, 64.4% men. Concentric remodeling carried the highest frequency, 49.2%, followed by concentric hypertrophy, 30.7%, normal pattern, 15.5%, and eccentric hypertrophy, 4.1%. The frequency of abnormal left ventricular RWT (80.4%) was significantly higher than that of abnormal LVMI (35.3%), (McNemar P < 0.05). In this group of non-cardioembolic stroke patients, abnormal LV remodeling as assessed by relative wall thickness is very frequent. As RWT was often found without increased LV mass, the abnormal left ventricular geometry may be missed if RWT is not measured or reported. PMID:25997067

  16. Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig.

    PubMed

    Beaumont, Eric; Wright, Gary L; Southerland, Elizabeth M; Li, Ying; Chui, Ray; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

    2016-05-15

    Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15-20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

  17. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    PubMed Central

    Dewald, Daniela; Schmitz, Eva J.; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT−/−)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT−/−-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2−/−-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT−/−-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2−/−-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  18. Mechanism of chromatin remodeling.

    PubMed

    Lorch, Yahli; Maier-Davis, Barbara; Kornberg, Roger D

    2010-02-23

    Results from biochemical and structural studies of the RSC chromatin-remodeling complex prompt a proposal for the remodeling mechanism: RSC binding to the nucleosome releases the DNA from the histone surface and initiates DNA translocation (through one or a small number of DNA base pairs); ATP binding completes translocation, and ATP hydrolysis resets the system. Binding energy thus plays a central role in the remodeling process. RSC may disrupt histone-DNA contacts by affecting histone octamer conformation and through extensive interaction with the DNA. Bulging of the DNA from the octamer surface is possible, and twisting is unavoidable, but neither is the basis of remodeling. PMID:20142505

  19. Left atrium remodeling after acute myocardial infarction (results of the GISSI-3 Echo Substudy).

    PubMed

    Popescu, Bogdan A; Macor, Franco; Antonini-Canterin, Francesco; Giannuzzi, Pantaleo; Temporelli, Pier L; Bosimini, Enzo; Gentile, Francesco; Maggioni, Aldo P; Tavazzi, Luigi; Piazza, Rita; Ascione, Luigi; Stoian, Ioana; Cervesato, Eugenio; Nicolosi, Gian L

    2004-05-01

    To evaluate the existence, timing, and determinants of post-infarction left atrial remodeling, we studied a subgroup of 514 patients from the Third Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Echo Substudy who underwent 4 serial 2-dimensional echocardiograms up to 6 months after acute myocardial infarction. This study is the first to demonstrate, in a large series of patients, the existence of early and late left atrial remodeling after low-risk acute myocardial infarction and the relation of left atrial remodeling to left ventricular remodeling. PMID:15110211

  20. Technique to avoid left ventricular outflow tract obstruction.

    PubMed

    Gualis, Javier; Castaño, Mario; Martínez-Comendador, Jose Manuel

    2016-06-01

    Preserving the subvalvular mitral valve apparatus during mitral valve replacement is extremely important to minimize progressive postoperative left ventricular remodeling and dysfunction. We describe a simple and reproducible surgical technique that prevents the complications that can occur after total mitral anterior leaflet preservation. PMID:26993109

  1. Cardiac remodelling and RAS inhibition.

    PubMed

    Ferrario, Carlos M

    2016-06-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  2. GPR55 Deletion in Mice Leads to Age-Related Ventricular Dysfunction and Impaired Adrenoceptor-Mediated Inotropic Responses

    PubMed Central

    Walsh, Sarah K.; Hector, Emma E.; Andréasson, Anne-Christine; Jönsson-Rylander, Ann-Cathrine; Wainwright, Cherry L.

    2014-01-01

    G protein coupled receptor 55 (GPR55) is expressed throughout the body, and although its exact physiological function is unknown, studies have suggested a role in the cardiovascular system. In particular, GPR55 has been proposed as mediating the haemodynamic effects of a number of atypical cannabinoid ligands; however this data is conflicting. Thus, given the incongruous nature of our understanding of the GPR55 receptor and the relative paucity of literature regarding its role in cardiovascular physiology, this study was carried out to examine the influence of GPR55 on cardiac function. Cardiac function was assessed via pressure volume loop analysis, and cardiac morphology/composition assessed via histological staining, in both wild-type (WT) and GPR55 knockout (GPR55−/−) mice. Pressure volume loop analysis revealed that basal cardiac function was similar in young WT and GPR55−/− mice. In contrast, mature GPR55−/− mice were characterised by both significant ventricular remodelling (reduced left ventricular wall thickness and increased collagen deposition) and systolic dysfunction when compared to age-matched WT mice. In particular, the load-dependent parameter, ejection fraction, and the load-independent indices, end-systolic pressure-volume relationship (ESPVR) and Emax, were all significantly (P<0.05) attenuated in mature GPR55−/− mice. Furthermore, GPR55−/− mice at all ages were characterised by a reduced contractile reserve. Our findings demonstrate that mice deficient in GPR55 exhibit maladaptive adrenergic signalling, as evidenced by the reduced contractile reserve. Furthermore, with age these mice are characterised by both significant adverse ventricular remodelling and systolic dysfunction. Taken together, this may suggest a role for GPR55 in the control of adrenergic signalling in the heart and potentially a role for this receptor in the pathogenesis of heart failure. PMID:25275556

  3. Irx3 is required for postnatal maturation of the mouse ventricular conduction system

    PubMed Central

    Kim, Kyoung-Han; Rosen, Anna; Hussein, Samer M. I.; Puviindran, Vijitha; Korogyi, Adam S.; Chiarello, Carmelina; Nagy, Andras; Hui, Chi-chung; Backx, Peter H.

    2016-01-01

    The ventricular conduction system (VCS) orchestrates the harmonious contraction in every heartbeat. Defects in the VCS are often associated with life-threatening arrhythmias and also promote adverse remodeling in heart disease. We have previously established that the Irx3 homeobox gene regulates rapid electrical propagation in the VCS by modulating the transcription of gap junction proteins Cx40 and Cx43. However, it is unknown whether other factors contribute to the conduction defects observed in Irx3 knockout (Irx3−/−) mice. In this study, we show that during the early postnatal period, Irx3−/− mice develop morphological defects in the VCS which are temporally dissociated from changes in gap junction expression. These morphological defects were accompanied with progressive changes in the cardiac electrocardiogram including right bundle branch block. Hypoplastic VCS was not associated with increased apoptosis of VCS cardiomyocytes but with a lack of recruitment and maturation of ventricular cardiomyocytes into the VCS. Computational analysis followed by functional verification revealed that Irx3 promotes VCS-enriched transcripts targeted by Nkx2.5 and/or Tbx5. Altogether, these results indicate that, in addition to ensuring the appropriate expression of gap junctional channels in the VCS, Irx3 is necessary for the postnatal maturation of the VCS, possibly via its interactions with Tbx5 and Nkx2.5. PMID:26786475

  4. Intradialytic Hypotension and Cardiac Remodeling: A Vicious Cycle

    PubMed Central

    Huang, Jenq-Wen; Yen, Chung-Jen

    2015-01-01

    Hemodynamic instability during hemodialysis is a common but often underestimated issue in the nephrologist practice. Intradialytic hypotension, namely, a decrease of systolic or mean blood pressure to a certain level, prohibits the safe and smooth achievement of ultrafiltration and solute removal goal in chronic dialysis patients. Studies have elucidated the potential mechanisms involved in the development of Intradialytic hypotension, including excessive ultrafiltration and loss of compensatory mechanisms for blood pressure maintenance. Cardiac remodeling could also be one important piece of the puzzle. In this review, we intend to discuss the role of cardiac remodeling, including left ventricular hypertrophy, in the development of Intradialytic hypotension. In addition, we will also provide evidence that a bidirectional relationship might exist between Intradialytic hypotension and left ventricular hypertrophy in chronic dialysis patients. A more complete understanding of the complex interactions in between could assist the readers in formulating potential solutions for the reduction of both phenomena. PMID:25654122

  5. Assessment of right ventricular systolic function by tissue Doppler echocardiography.

    PubMed

    Kjærgaard, Jesper

    2012-03-01

    -massive pulmonary embolism quantifies degree of RV dysfunction, and supports the existence of the McConnell sign of mid-ventricular RV dysfunction. Echocardiographic signs of RV dysfunction are present if > 25% of the pulmonary vascular bed is obstructed. However, Tissue Doppler echocardiography and deformation analysis has no independent value over other clinical and quantitative echocardiographic measures of RV size, pressure and function in these patients [IV and V]. Regional deformation of the RV free wall has significant prognostic importance in a population suspected of first non-massive pulmonary embolism, and is significantly associated with adverse events in patients with proven pulmonary embolism, however, it does not add to the information gained from other quantitative echocardiographic measures of LV and RV function and pressure [VI]. Changes in tissue Doppler based measures of RV systolic function can be used to monitor the effect of selective vasodilation by phosphodiestares-5 inhibition in hypoxic pulmonary hypertension and exercise in normal individuals. Phosphodiestares-5 inhibition by sildenafil may predominantly be effective during hypoxia in resting conditions, and may improve the blunted response in RV contractility seen with exercise in hypoxia [VII]. Reduced RV free wall deformation can be quantified by tissue Doppler echocardiography in patients with confirmed Arrhythmogenic Right Ventricular Cardiomyopathy, but the clinical application of the technique may be limited by considerable overlap with normal values [VIII]. Acute RV volume loading in free pulmonary regurgitation is associated with abrupt geometric changes in the RV structure including significant dilatation, but is well tolerated with only mild reduction in measures of global RV systolic function as estimated by 2D echocardiography in an experimental animal model. Regional RV myocardial function is also only mildly reduced. Also no differences in global or regional RV function can be observed

  6. Effects of carvedilol on left ventricular function, mass, and scintigraphic findings in isolated left ventricular non-compaction

    PubMed Central

    Toyono, M; Kondo, C; Nakajima, Y; Nakazawa, M; Momma, K; Kusakabe, K

    2001-01-01

    A four month old infant with isolated left ventricular non-compaction was treated with carvedilol. Haemodynamic studies and various types of imaging—including echocardiography, radiographic angiography, magnetic resonance imaging, and single photon emission computed tomography with 201Tl, 123I-β-methyliodophenylpentadecanoic acid (BMIPP), and 123I-metaiodobenzylguanidine (MIBG)—were performed before and 14 months after treatment. Left ventricular ejection fraction increased from 30% to 57%, and left ventricular end diastolic volume, end systolic volume, and end diastolic pressure showed striking reductions during treatment. Left ventricular mass decreased to about two thirds of the baseline value after treatment. Per cent wall thickening increased after carvedilol in the segments corresponding to non-compacted myocardium. A mismatch between 201Tl and BMIPP uptake in the area of non-compaction observed before carvedilol disappeared after treatment. Impaired sympathetic neuronal function shown by MIBG recovered after treatment. Thus carvedilol had beneficial effects on left ventricular function, hypertrophy, and both metabolic and adrenergic abnormalities in isolated left ventricular non-compaction.


Keywords: isolated left ventricular non-compaction; carvedilol; cardiac sympathetic nerve; ventricular remodelling PMID:11410581

  7. Anti‐Remodeling and Anti‐Fibrotic Effects of the Neuregulin‐1β Glial Growth Factor 2 in a Large Animal Model of Heart Failure

    PubMed Central

    Galindo, Cristi L.; Kasasbeh, Ehab; Murphy, Abigail; Ryzhov, Sergey; Lenihan, Sean; Ahmad, Farhaan A.; Williams, Philip; Nunnally, Amy; Adcock, Jamie; Song, Yanna; Harrell, Frank E.; Tran, Truc‐Linh; Parry, Tom J.; Iaci, Jen; Ganguly, Anindita; Feoktistov, Igor; Stephenson, Matthew K.; Caggiano, Anthony O.; Sawyer, Douglas B.; Cleator, John H.

    2014-01-01

    Background Neuregulin‐1β (NRG‐1β) is a growth factor critical for cardiac development and repair with therapeutic potential for heart failure. We previously showed that the glial growth factor 2 (GGF2) isoform of NRG‐1β improves cardiac function in rodents after myocardial infarction (MI), but its efficacy in a large animal model of cardiac injury has not been examined. We therefore sought to examine the effects of GGF2 on ventricular remodeling, cardiac function, and global transcription in post‐MI swine, as well as potential mechanisms for anti‐remodeling effects. Methods and Results MI was induced in anesthetized swine (n=23) by intracoronary balloon occlusion. At 1 week post‐MI, survivors (n=13) received GGF2 treatment (intravenous, biweekly for 4 weeks; n=8) or were untreated (n=5). At 5 weeks post‐MI, fractional shortening was higher (32.8% versus 25.3%, P=0.019), and left ventricular (LV) end‐diastolic dimension lower (4.5 versus 5.3 cm, P=0.003) in GGF2‐treated animals. Treatment altered expression of 528 genes, as measured by microarrays, including collagens, basal lamina components, and matricellular proteins. GGF2‐treated pigs exhibited improvements in LV cardiomyocyte mitochondria and intercalated disk structures and showed less fibrosis, altered matrix structure, and fewer myofibroblasts (myoFbs), based on trichrome staining, electron microscopy, and immunostaining. In vitro experiments with isolated murine and rat cardiac fibroblasts demonstrate that NRG‐1β reduces myoFbs, and suppresses TGFβ‐induced phospho‐SMAD3 as well as αSMA expression. Conclusions These results suggest that GGF2/NRG‐1β prevents adverse remodeling after injury in part via anti‐fibrotic effects in the heart. PMID:25341890

  8. Neutrophil roles in left ventricular remodeling following myocardial infarction

    PubMed Central

    2013-01-01

    Polymorphonuclear granulocytes (PMNs; neutrophils) serve as key effector cells in the innate immune system and provide the first line of defense against invading microorganisms. In addition to producing inflammatory cytokines and chemokines and undergoing a respiratory burst that stimulates the release of reactive oxygen species, PMNs also degranulate to release components that kill pathogens. Recently, neutrophil extracellular traps have been shown to be an alternative way to trap microorganisms and contain infection. PMN-derived granule components are also involved in multiple non-infectious inflammatory processes, including the response to myocardial infarction (MI). In this review, we will discuss the biological characteristics, recruitment, activation, and removal of PMNs, as well as the roles of PMN-derived granule proteins in inflammation and innate immunity, focusing on the MI setting when applicable. We also discuss future perspectives that will direct research in PMN biology. PMID:23731794

  9. Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats

    PubMed Central

    Fernandes, S; Naumova, AV; Zhu, WZ; Laflamme, MA; Gold, J; Murry, CE

    2010-01-01

    Background Previous studies indicated that, in an acute myocardial infarction model, human embryonic stem cell-derived cardiomyocytes (hESC-CM) injected with a pro-survival cocktail (PSC) can preserve contractile function. Because patients with established heart failure may also benefit from cell transplantation, we evaluated the physiological effects of hESC-CM transplanted into a chronic model of myocardial infarction. Methods and Results Intramyocardial injection of hESC-CM with PSC was performed in nude rats at 1 month following ischemia-reperfusion. The left ventricular function of hESC-CM injected rats was evaluated at 1, 2 and 3 months after the cell injection procedure and was compared to 3 control groups (rats injected with serum-free media, PSC-only, or non-cardiac human cells in PSC). Histology at 3 months revealed that human cardiomyocytes survive, develop increased sarcomere organization and are still proliferating. Despite successful engraftment, both echocardiography and MRI analyses showed no significant difference in left ventricular structure or function between these 4 groups at any time point of the study, suggesting that human cardiomyocytes do not affect cardiac remodeling in a rat model of chronic myocardial infarction. Conclusion When injected into a chronic infarct model, hESC-CM can engraft, survive and form grafts with striated cardiomyocytes at least as well as was previously observed in an acute myocardial infarction model. However, although hESC-CM transplantation can attenuate the progression of heart failure in an acute model, the same hESC-CM injection protocol is insufficient to restore heart function or to alter adverse remodeling of a chronic myocardial infarction model. PMID:20854826

  10. Effectiveness and Safety of Transcatheter Closure of Perimembranous Ventricular Septal Defects in Adults.

    PubMed

    Wang, Jianming; Zuo, Jian; Yu, Shiqiang; Yi, Dinghua; Yang, Xiuling; Zhu, Xianyang; Li, Jun; Yang, Lifang; Xiong, Lize; Ge, Shuping; Ren, Jun; Yang, Jian

    2016-03-15

    This study was designed to determine the long-term safety and efficacy of using modified double-disk occluders for perimembranous ventricular septal defect (pmVSD) closure in adults. From January 2004 to December 2014, 337 adults with pmVSDs were treated through transcatheter intervention using 2 types of double-disk occluders; 302 patients received a symmetrical concentric pmVSD occluder, and 35 patients received an asymmetrical concentric pmVSD occluder. All patients were followed up through electrocardiography and transthoracic echocardiography until June 2015. The success rate was 100% for both procedures. During the median 71-month follow-up period, no cases of infective endocarditis, cerebrovascular accidents, heart failure, or death occurred. Two major adverse events (0.6%) were recorded: complete atrioventricular block requiring surgical treatment in one patient and severe tricuspid valvular regurgitation requiring surgical repair in another patient. Cardiac conduction block was the most common minor adverse event. The mean left ventricular (LV) end-diastolic volume decreased from 96.6 ± 23.2 ml before intervention to 86.0 ± 22.0 ml (p <0.05) at the 6-month follow-up visit. Previously enlarged LV chambers decreased to normal sizes during the follow-up period. In conclusion, transcatheter closure of pmVSDs using modified double-disk occluders was both safe and effective and yielded excellent long-term results in adults. The potential benefits of this intervention included remodeling of the heart, a reduced incidence of infective endocarditis and prevention of LV volume overload. PMID:26796197

  11. Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction

    PubMed Central

    Ciampi, Quirino; Villari, Bruno

    2007-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Echocardiography represents the "gold standard" in the assessment of LV systolic dysfunction and in the recognition of systolic heart failure, since dilatation of the LV results in alteration of intracardiac geometry and hemodynamics leading to increased morbidity and mortality. The functional mitral regurgitation is a consequence of adverse LV remodelling that occurs with a structurally normal valve and it is a marker of adverse prognosis. Diastolic dysfunction plays a major role in signs and symptoms of HF and in the risk stratification, and provides prognostic information independently in HF patients and impaired systolic function. Ultrasound lung comets are a simple echographic sign of extravascular lung water, more frequently associated with left ventricular diastolic and/or systolic dysfunction, which can integrate the clinical and pathophysiological information provided by conventional echocardiography and provide a useful information for prognostic stratification of HF patients. Contractile reserve is defined as the difference between values of an index of left ventricular contractility during peak stress and its baseline values and the presence of myocardial viability predicts a favorable outcome. A non-invasive echocardiographic method for the evaluation of force-frequency relationship has been proposed to assess the changes in contractility during stress echo. In conclusion, in HF patients, the evaluation of systolic, diastolic function and myocardial contractile reserve plays a fundamental role in the risk stratification. The highest risk is present in HF patients with a heart that is weak, big, noisy, stiff and wet. PMID:17910744

  12. Ranolazine reduces remodeling of the right ventricle and provoked arrhythmias in rats with pulmonary hypertension.

    PubMed

    Liles, John T; Hoyer, Kirsten; Oliver, Jason; Chi, Liguo; Dhalla, Arvinder K; Belardinelli, Luiz

    2015-06-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that often results in right ventricular (RV) failure and death. During disease progression, structural and electrical remodeling of the right ventricle impairs pump function, creates proarrhythmic substrates, and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in patients with PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an antianginal, anti-ischemic drug that has cardioprotective effects in experimental and clinical settings of left-sided heart dysfunction. RAN also has antiarrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. We therefore hypothesized that RAN could reduce the maladaptive structural and electrical remodeling of the right ventricle and could prevent triggered ventricular arrhythmias in the monocrotaline rat model of PAH. Indeed, in both in vivo and ex vivo experimental settings, chronic RAN treatment reduced electrical heterogeneity (right ventricular-left ventricular action potential duration dispersion), shortened heart-rate corrected QT intervals in the right ventricle, and normalized RV dysfunction. Chronic RAN treatment also dose-dependently reduced ventricular hypertrophy, reduced circulating levels of B-type natriuretic peptide, and decreased the expression of fibrotic markers. In addition, the acute administration of RAN prevented isoproterenol-induced ventricular tachycardia/ventricular fibrillation and subsequent cardiovascular death in rats with established PAH. These results support the notion that RAN can improve the electrical and functional properties of the right ventricle, highlighting its potential benefits in the setting of RV impairment. PMID:25770134

  13. Arrhythmogenic Right Ventricular Cardiomyopathy: Considerations from in Silico Experiments

    PubMed Central

    Wilders, Ronald

    2012-01-01

    Objective: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with remodeling of gap junctions and also, although less well-defined, down-regulation of the fast sodium current. The gap junction remodeling and down-regulation of sodium current have been proposed as contributors to arrhythmogenesis in ARVC by slowing conduction. The objective of the present study was to assess the amount of conduction slowing due to the observed gap junction remodeling and down-regulation of sodium current. Methods: The effects of (changes in) gap junctional conductance, cell dimensions, and sodium current on both longitudinal and transversal conduction velocity were tested by simulating action potential propagation in linear strands of human ventricular cells that were either arranged end-to-end or side-by-side. Results: A 50% reduction in gap junction content, as commonly observed in ARVC, gives rise to an 11% decrease in longitudinal conduction velocity and a 29% decrease in transverse conduction velocity. A down-regulation of the sodium current through a 50% decrease in peak current density as well as a −15 mV shift in steady-state inactivation, as observed in an experimental model of ARVC, decreases conduction velocity in either direction by 32%. In combination, the gap junction remodeling and down-regulation of sodium current result in a 40% decrease in longitudinal conduction velocity and a 52% decrease in transverse conduction velocity. Conclusion: The gap junction remodeling and down-regulation of sodium current do result in conduction slowing, but heterogeneity of gap junction remodeling, in combination with down-regulation of sodium current, rather than gap junction remodeling per se may be a critical factor in arrhythmogenesis in ARVC. PMID:22754532

  14. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects

    PubMed Central

    Rajagopalan, Viswanathan; Zhang, Youhua; Ojamaa, Kaie; Chen, Yue-feng; Pingitore, Alessandro; Pol, Christine J.; Saunders, Debra; Balasubramanian, Krithika; Towner, Rheal A.; Gerdes, A. Martin

    2016-01-01

    Background A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. Methods and Results Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. Conclusions Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans. PMID:26981865

  15. Immunoregulation of bone remodelling

    PubMed Central

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-01-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also. PMID:22837895

  16. Pediatric ventricular assist devices.

    PubMed

    Adachi, Iki; Burki, Sarah; Zafar, Farhan; Morales, David Luis Simon

    2015-12-01

    The domain of pediatric ventricular assist device (VAD) has recently gained considerable attention. Despite the fact that, historically, the practice of pediatric mechanical circulatory support (MCS) has lagged behind that of adult patients, this gap between the two groups is narrowing. Currently, the Berlin EXCOR VAD is the only pediatric-specific durable VAD approved by the U.S Food and Drug Administration (FDA). The prospective Berlin Heart trial demonstrated a successful outcome, either bridge to transplantation (BTT), or in rare instances, bridge to recovery, in approximately 90% of children. Also noted during the trial was, however, a high incidence of adverse events such as embolic stroke, bleeding and infection. This has incentivized some pediatric centers to utilize adult implantable continuous-flow devices, for instance the HeartMate II and HeartWare HVAD, in children. As a result of this paradigm shift, the outlook of pediatric VAD support has dramatically changed: Treatment options previously unavailable to children, including outpatient management and even destination therapy, have now been becoming a reality. The sustained demand for continued device miniaturization and technological refinements is anticipated to extend the range of options available to children-HeartMate 3 and HeartWare MVAD are two examples of next generation VADs with potential pediatric application, both of which are presently undergoing clinical trials. A pediatric-specific continuous-flow device is also on the horizon: the redesigned Infant Jarvik VAD (Jarvik 2015) is undergoing pre-clinical testing, with a randomized clinical trial anticipated to follow thereafter. The era of pediatric VADs has begun. In this article, we discuss several important aspects of contemporary VAD therapy, with a particular focus on challenges unique to the pediatric population. PMID:26793341

  17. Pediatric ventricular assist devices

    PubMed Central

    Burki, Sarah; Zafar, Farhan; Morales, David Luis Simon

    2015-01-01

    The domain of pediatric ventricular assist device (VAD) has recently gained considerable attention. Despite the fact that, historically, the practice of pediatric mechanical circulatory support (MCS) has lagged behind that of adult patients, this gap between the two groups is narrowing. Currently, the Berlin EXCOR VAD is the only pediatric-specific durable VAD approved by the U.S Food and Drug Administration (FDA). The prospective Berlin Heart trial demonstrated a successful outcome, either bridge to transplantation (BTT), or in rare instances, bridge to recovery, in approximately 90% of children. Also noted during the trial was, however, a high incidence of adverse events such as embolic stroke, bleeding and infection. This has incentivized some pediatric centers to utilize adult implantable continuous-flow devices, for instance the HeartMate II and HeartWare HVAD, in children. As a result of this paradigm shift, the outlook of pediatric VAD support has dramatically changed: Treatment options previously unavailable to children, including outpatient management and even destination therapy, have now been becoming a reality. The sustained demand for continued device miniaturization and technological refinements is anticipated to extend the range of options available to children—HeartMate 3 and HeartWare MVAD are two examples of next generation VADs with potential pediatric application, both of which are presently undergoing clinical trials. A pediatric-specific continuous-flow device is also on the horizon: the redesigned Infant Jarvik VAD (Jarvik 2015) is undergoing pre-clinical testing, with a randomized clinical trial anticipated to follow thereafter. The era of pediatric VADs has begun. In this article, we discuss several important aspects of contemporary VAD therapy, with a particular focus on challenges unique to the pediatric population. PMID:26793341

  18. Remodeling and Shuttling

    PubMed Central

    Rodrigueza, Wendi V.; Williams, Kevin Jon; Rothblat, George H.; Phillips, Michael C.

    2016-01-01

    In normal physiology, cells are exposed to cholesterol acceptors of different sizes simultaneously. The current study examined the possible interactions between two different classes of acceptors, one large (large unilamellar phospholipid vesicles, LUVs) and one small (HDL or other small acceptors), added separately or in combination to Fu5AH rat hepatoma cells. During a 24-hour incubation, LUVs of palmitoyl-oleoyl phosphatidylcholine at 1 mg phospholipid (PL) per milliliter extracted ≈20% of cellular unesterified cholesterol (UC) label and mass in a slow, continuous fashion (half-time [t½] for UC efflux was ≈50 hours) and human HDL3 at 25 μg PL per milliliter extracted ≈15% cellular UC label with no change in cellular cholesterol mass (t½ of ≈8 hours). In contrast, the combination of LUVs and HDL3 extracted over 90% of UC label (t½ of ≈4 hours) and ≈50% of the UC mass, indicating synergy. To explain this synergy, specific particle interactions were examined, namely, remodeling, in which the two acceptors alter each other’s composition and thus the ability to mobilize cellular cholesterol, and shuttling, in which the small acceptor ferries cholesterol from cells to the large acceptor. To examine remodeling, LUVs and HDL were coincubated and reisolated before application to cells. This HDL became UC depleted, PL enriched, and lost a small amount of apolipoprotein A-I. Compared with equivalent numbers of control HDL particles, remodeled HDL caused faster efflux (t½ ≈4 hours) and exhibited a greater capacity to sequester cellular cholesterol over 24 hours (≈38% versus ≈15% for control HDL), consistent with their enrichment in PL. Remodeled LUVs still extracted ≈20% of cellular UC. Thus, remodeling accounted for some but not all of the synergy between LUVs and HDL. To examine shuttling, several approaches were used. First, reisolation of particles after an 8-hour exposure to cells revealed that HDL contained very little of the cellular UC

  19. Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis.

    PubMed

    Frunza, Olga; Russo, Ilaria; Saxena, Amit; Shinde, Arti V; Humeres, Claudio; Hanif, Waqas; Rai, Vikrant; Su, Ya; Frangogiannis, Nikolaos G

    2016-05-01

    The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response. PMID:26948424

  20. Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity.

    PubMed

    Martínez-Martínez, Ernesto; López-Ándres, Natalia; Jurado-López, Raquel; Rousseau, Elodie; Bartolomé, Mará Visitación; Fernández-Celis, Amaya; Rossignol, Patrick; Islas, Fabian; Antequera, Alfonso; Prieto, Santiago; Luaces, María; Cachofeiro, Victoria

    2015-11-01

    Remodeling, diastolic dysfunction, and arterial stiffness are some of the alterations through which obesity affects the cardiovascular system. Fibrosis and inflammation are important mechanisms underlying cardiovascular remodeling, although the precise promoters involved in these processes are still unclear. Galectin-3 (Gal-3) induces inflammation and fibrosis in the cardiovascular system. We have investigated the potential role of Gal-3 in cardiac damage in morbidly obese patients, and we have evaluated the protective effect of the Gal-3 inhibition in the occurrence of cardiovascular fibrosis and inflammation in an experimental model of obesity. Morbid obesity is associated with alterations in cardiac remodeling, mainly left ventricular hypertrophy and diastolic dysfunction. Obesity and hypertension are the main determinants of left ventricular hypertrophy. Insulin resistance, left ventricular hypertrophy, and circulating levels of C-reactive protein and Gal-3 are associated with a worsening of diastolic function in morbidly obese patients. Obesity upregulates Gal-3 production in the cardiovascular system in a normotensive animal model of diet-induced obesity by feeding for 6 weeks a high-fat diet (33.5% fat). Gal-3 inhibition with modified citrus pectin (100 mg/kg per day) reduced cardiovascular levels of Gal-3, total collagen, collagen I, transforming and connective growth factors, osteopontin, and monocyte chemoattractant protein-1 in the heart and aorta of obese animals without changes in body weight or blood pressure. In morbidly obese patients, Gal-3 levels are associated with diastolic dysfunction. In obese animals, Gal-3 blockade decreases cardiovascular fibrosis and inflammation. These data suggest that Gal-3 could be a novel therapeutic target in cardiac fibrosis and inflammation associated with obesity. PMID:26351031

  1. Compensatory Effect between Aortic Stiffening and Remodelling during Ageing

    PubMed Central

    Guala, Andrea; Camporeale, Carlo; Ridolfi, Luca

    2015-01-01

    The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases. PMID:26426360

  2. Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction.

    PubMed

    Li, Chang-Yi; Li, Yi-Gang

    2015-01-01

    Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403

  3. Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction

    PubMed Central

    Li, Chang-Yi; Li, Yi-Gang

    2015-01-01

    Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403

  4. [Treatment of ventricular tachycardia].

    PubMed

    Iturralde Torres, P

    2001-01-01

    Evaluation and management of postinfarct ventricular tachycardia has changed dramatically in the past two decades. The introduction of the implantable cardioverter defibrillator has played a major role in this change, alternating both, the purpose of the patients evaluation and treatment options. Episodes of sustained ventricular tachycardia can occur in a variety of clinical settings; the most common of which is the patient who has suffered a myocardial infarction. In this paper, I explore the causes and effects of some of these changes and review current strategies, specially the radiofrequency catheter ablation, for the management of the patient with postinfarct ventricular tachycardia. PMID:11565352

  5. Remodeling with the sun

    SciTech Connect

    Bodzin, S.

    1997-05-01

    Remodeling is the perfect time to improve daylighting, direct gain heating and shading with passive solar techniques. It can also provide the best opportunity to add solar water heating or even photoboltaics to a home. This article describes addition of such energy efficient plans to a home in terms of what is needed and what the benefits are: adding windows, North glass, east and west glass, south glass, daylighting, the roof, shingles and roofing tiles, walls and floors, solar hot water, photovoltaics. Two side bars discuss the sunplace: a passive solar room and angles and overhangs.

  6. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    PubMed Central

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  7. Arginase inhibition prevents inflammation and remodeling in a guinea pig model of chronic obstructive pulmonary disease.

    PubMed

    Pera, T; Zuidhof, A B; Smit, M; Menzen, M H; Klein, T; Flik, G; Zaagsma, J; Meurs, H; Maarsingh, H

    2014-05-01

    Airway inflammation and remodeling are major features of chronic obstructive pulmonary disease (COPD), whereas pulmonary hypertension is a common comorbidity associated with a poor disease prognosis. Recent studies in animal models have indicated that increased arginase activity contributes to features of asthma, including allergen-induced airway eosinophilia and mucus hypersecretion. Although cigarette smoke and lipopolysaccharide (LPS), major risk factors for COPD, may increase arginase expression, the role of arginase in COPD is unknown. This study aimed to investigate the role of arginase in pulmonary inflammation and remodeling using an animal model of COPD. Guinea pigs were instilled intranasally with LPS or saline twice weekly for 12 weeks and pretreated by inhalation of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) or vehicle. Repeated LPS exposure increased lung arginase activity, resulting in increased l-ornithine/l-arginine and l-ornithine/l-citrulline ratios. Both ratios were reversed by ABH. ABH inhibited the LPS-induced increases in pulmonary IL-8, neutrophils, and goblet cells as well as airway fibrosis. Remarkably, LPS-induced right ventricular hypertrophy, indicative of pulmonary hypertension, was prevented by ABH. Strong correlations were found between arginase activity and inflammation, airway remodeling, and right ventricular hypertrophy. Increased arginase activity contributes to pulmonary inflammation, airway remodeling, and right ventricular hypertrophy in a guinea pig model of COPD, indicating therapeutic potential for arginase inhibitors in this disease. PMID:24563530

  8. The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: Results of the REVERSE study

    PubMed Central

    Gold, Michael R.; Daubert, Claude; Abraham, William T.; Ghio, Stefano; Sutton, Martin St. John; Hudnall, John Harrison; Cerkvenik, Jeffrey; Linde, Cecilia

    2015-01-01

    BACKGROUND Cardiac resynchronization therapy (CRT) reduces mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure (HF). The magnitude of reverse remodeling predicts survival with many HF medical therapies. However, there are few studies assessing the effect of remodeling on long-term survival with CRT. OBJECTIVE The purpose of this study was to assess the effect of CRT-induced reverse remodeling on long-term survival in patients with mildly symptomatic heart failure. METHODS The REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction trial was a multicenter, double-blind, randomized trial of CRT in patients with mild HF. Long-term follow-up of 5 years was preplanned. The present analysis was restricted to the 353 patients who were randomized to the CRT ON group with paired echocardiographic studies at baseline and 6 months post-implantation. The left ventricular end-systolic volume index (LVESVi) was measured in the core laboratory and was an independently powered end point of the REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction trial. RESULTS A 68% reduction in mortality was observed in patients with ≥15% decrease in LVESVi compared to the rest of the patients (P = .0004). Multivariable analysis showed that the change in LVESVi was a strong independent predictor (P = .0002), with a 14% reduction in mortality for every 10% decrease in LVESVi. Other remodeling parameters such as left ventricular enddiastolic volume index and ejection fraction had a similar association with mortality. CONCLUSION The change in left ventricular end-systolic volume after 6 months of CRT is a strong independent predictor of long-term survival in mild HF. PMID:25460860

  9. Antagonism of Stem Cell Factor/c-kit Signaling Attenuates Neonatal Chronic Hypoxia-Induced Pulmonary Vascular Remodeling

    PubMed Central

    Young, Karen C; Torres, Eneida; Hehre, Dorothy; Wu, Shu; Suguihara, Cleide; Hare, Joshua M.

    2015-01-01

    Background Accumulating evidence suggests that c-kit positive cells are present in the remodeled pulmonary vasculature bed of patients with pulmonary hypertension (PH). Whether stem cell factor (SCF)/ c-kit regulated pathways potentiate pulmonary vascular remodeling is unknown. Here, we tested the hypothesis that attenuated c-kit signaling would decrease chronic hypoxia-induced pulmonary vascular remodeling by decreasing pulmonary vascular cell mitogenesis. Methods Neonatal FVB/NJ mice treated with non-immune IgG (PL), or c-kit neutralizing antibody (ACK2) as well as c-kit mutant mice (WBB6F1- Kit W− v/ +) and their congenic controls, were exposed to normoxia (FiO2=0.21) or hypoxia (FiO2=0.12) for two weeks. Following this exposure, right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), pulmonary vascular cell proliferation and remodeling were evaluated. Results As compared to chronically hypoxic controls, c-kit mutant mice had decreased RVSP, RVH, pulmonary vascular remodeling and proliferation. Consistent with these findings, administration of ACK2 to neonatal mice with chronic hypoxia-induced PH decreased RVSP, RVH, pulmonary vascular cell proliferation and remodeling. This attenuation in PH was accompanied by decreased extracellular signal-regulated protein kinase (ERK) 1/2 activation. Conclusion SCF/c-kit signaling may potentiate chronic hypoxia-induced vascular remodeling by modulating ERK activation. Inhibition of c-kit activity may be a potential strategy to alleviate PH. PMID:26705118

  10. To Remodel or To Build?

    ERIC Educational Resources Information Center

    Rosenblum, Todd

    2009-01-01

    The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

  11. No-Regrets Remodeling, 2nd Edition

    SciTech Connect

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  12. Toll-like Receptor 4 Mediates the Inflammatory Responses and Matrix Protein Remodeling in Remote Non-Ischemic Myocardium in a Mouse Model of Myocardial Ischemia and Reperfusion

    PubMed Central

    Zhai, Yufeng; Ao, Lihua; Cleveland, Joseph C.; Zeng, Qingchun; Reece, T. Brett; Fullerton, David A.; Meng, Xianzhong

    2015-01-01

    The signaling mechanism that mediates inflammatory responses in remote non-ischemic myocardium following regional ischemia/reperfusion (I/R) remains incompletely understood. Myocardial Toll-like receptor 4 (TLR4) can be activated by multiple proteins released from injured cells and plays a role in myocardial inflammation and injury expansion. We tested the hypothesis that TLR4 occupies an important role in mediating the inflammatory responses and matrix protein remodeling in the remote non-ischemic myocardium following regional I/R injury. Methods and results: TLR4-defective (C3H/HeJ) and TLR4-competent (C3H/HeN) mice were subjected to coronary artery ligation (30 min) and reperfusion for 1, 3, 7 or 14 days. In TLR4-competent mice, levels of monocyte chemoattractant protein -1 (MCP-1), keratinocyte chemoattractant (KC), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were elevated in the remote non-ischemic myocardium at day 1, 3, and 7 of reperfusion. Levels of collagen I, collagen IV, matrix metalloproteinase (MMP) 2 and MMP 9 were increased in the remote non-ischemic myocardium at day 7 and 14 of reperfusion. MMP 2 and MMP 9 activities were also increased. TLR4 deficiency resulted in a moderate reduction in myocardial infarct size. However, it markedly downgraded the changes in the levels of chemokines, adhesion molecules and matrix proteins in the remote non-ischemic myocardium. Further, left ventricular function at day 14 was significantly improved in TLR4-defective mice. In conclusion, TLR4 mediates the inflammatory responses and matrix protein remodeling in the remote non-ischemic myocardium following regional myocardial I/R injury and contributes to the mechanism of adverse cardiac remodeling. PMID:25823011

  13. Left Ventricular Assist Devices

    PubMed Central

    2004-01-01

    -hospitalization due to adverse events. Post-transplant survival rates for LVAD-bridged patients were similar to or better than the survival rates of patients bridged by medical therapy. LVAD support has been associated with serious adverse events, including infection (median 53%, range 6%–72%), bleeding (8.6%–48%, median 35%), thromboembolism (5%–37%), neurologic disorders (7%–28%), right ventricular failure (11%–26%), organ dysfunction (5%–50%) and hemolysis (6%–20%). Bleeding tends to occur in the first few post-implant days and is rare thereafter. It is fatal in 2%–7% of patients. Infection and thromboembolism occurred throughout the duration of the implant, though their frequency tended to diminish with time. Device malfunction has been identified as one of the major complications. Fatalities directly attributable to the devices were about 1% in short-term LVAD use. However, mechanical failure was the second most frequent cause of death in patients on prolonged LVAD support. Malfunctions were mainly associated with the external components, and often could be replaced by backed up components. LVAD has been used as a bridge-to-recovery in patients suffering from acute cardiogenic shock due to cardiomyopathy, myocarditis or cardiotomy. The survival rates were reported to be lower than in bridge-to-transplant (median 26%). Some of the bridge-to-recovery patients (14%–75%) required a heart transplant or remained on prolonged LVAD support. According to an expert in the field, experience with LVAD as a bridge-to-recovery technology has been more favourable in Germany than in North America, where it is not regarded as a major indication since evidence for its effectiveness in this setting is limited. LVAD has also been explored as a destination therapy. A small, randomized, controlled trial (level 2 evidence) showed that LVAD significantly increased the 1-year survival rate of patients with end-stage heart failure but were not eligible for a heart transplant (51% LVAD

  14. Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure

    PubMed Central

    Reis, José Rosino de Araújo Rocha; Cardoso, Juliano Novaes; Cardoso, Cristina Martins dos Reis; Pereira-Barretto, Antonio Carlos

    2015-01-01

    In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis. PMID:26131706

  15. Correlation of Left Ventricular Diastolic Function and Left Ventricular Geometry in Patients with Obstructive Sleep Apnoea Syndrome

    PubMed Central

    Wang, J; Zhang, H; Wu, C; Han, J; Guo, Z; Jia, C; Yang, L; Hao, Y; Xu, K; Liu, X; Si, J

    2015-01-01

    ABSTRACT Background: The aim of this study is to evaluate the correlation of the left ventricular diastolic function and the left ventricular geometry in patients with obstructive sleep apnoea syndrome (OSAS) by echocardiography. Methods: The 181 patients diagnosed with OSAS were divided into the normal geometry group (NG), the concentric remodelling group (CR), the eccentric hypertrophy group (EH) and the concentric hypertrophy group (CH). Pearson correlation analysis and multiple linear regression analysis were performed toward the correlation of the left ventricular diastolic function and the left ventricular geometry. Results: The E peak in the EH and CH group was significantly reduced, with significant difference; the E/A, Em, Am and Em/Am was reduced in the order of the CR, EH and CH groups, while E/Em was increased, and the difference was significant. Pearson correlation analysis revealed that the Em/Am showed significant negative correlations with the left ventricular mass index (LVMI) [r = −0.419] and relative wall thickness (RWT) [r = −0.289], while the E/Em was significantly positively correlated with the LVMI (r = 0.638) and RWT [r = 0.328] (p < 0.001). Multiple linear regression analysis revealed that LVMI and RWT had influence on the Em/Am and E/Em (r2 = 0.402, r2 = 0.107, p < 0.001). The left ventricular diastolic dysfunction was the worst in the CH group. Conclusions: There was correlation between the left ventricular diastolic dysfunction and the changes in cardiac geometry. PMID:26360680

  16. Mast Cell Inhibition Attenuates Cardiac Remodeling and Diastolic Dysfunction in Middle-aged, Ovariectomized Fischer 344 × Brown Norway Rats.

    PubMed

    Wang, Hao; da Silva, Jaqueline; Alencar, Allan; Zapata-Sudo, Gisele; Lin, Marina R; Sun, Xuming; Ahmad, Sarfaraz; Ferrario, Carlos M; Groban, Leanne

    2016-07-01

    The incidence of left ventricular diastolic dysfunction (LVDD) increases in women after menopause, yet the mechanisms are unclear. Because mast cells participate in the pathological processes of various cardiac diseases, we hypothesized that mast cell inhibition would protect against estrogen loss-induced LVDD. The mast cell stabilizer, cromolyn sodium (30 mg·kg·d), or vehicle was administered subcutaneously by osmotic minipump to ovariectomized (OVX) female Fischer 344 × Brown Norway (F344BN) rats starting at 4 weeks after surgery. Eight weeks after OVX, systolic blood pressure increased by 20% in OVX versus sham rats, and this effect was attenuated after 4 weeks of cromolyn treatment. Also, cromolyn mitigated the adverse reductions in myocardial relaxation (e') and increases in left ventricle (LV) filling pressures (E/e'), LV mass, wall thicknesses, and interstitial fibrosis from OVX. Although cardiac mast cell number was increased after OVX, cardiac chymase activity was not overtly altered by estrogen status and tended to decrease by cromolyn. Contrariwise, Ang II content was greater in hearts of OVX versus sham rats, and cromolyn attenuated this effect. Taken together, mast cell inhibition with cromolyn attenuates LV remodeling and LVDD in OVX-Fischer 344 × Brown Norway rats possibly through actions on the heart level and/or through vasodilatory effects at the vascular level. PMID:26981683

  17. Assessment of prevalence of left ventricular hypertrophy in hypertension.

    PubMed

    Korner, P I; Jennings, G L

    1998-06-01

    The reported prevalence of left ventricular hypertrophy (LVH) in human hypertension is much lower than that among animals with experimental hypertension. With current methods of determining left ventricular mass by M-mode echocardiography, the standard error of a single estimate is high and consequently so is the SD of the population distribution. This accounts for the large overlap in individual values of left ventricular mass index (LVMI) between hypertensive and normotensive groups. The high SD is due to the use of the cube algorithm for relating measurements made in a single plane to the whole left ventricle, and to the difference between actual and assumed left ventricular geometries. These are not problems with nuclear magnetic resonance imaging, which provides information about the entire left ventricle without assumptions about geometry. M-mode echocardiography is well suited for estimating differences between mean LVMI values for groups of subjects but it underestimates the prevalence of LVH. In most series only about 30% of hypertensives have been reported to have LVH. The estimated prevalence of structural remodelling is increased to 50-60% of the same group of subjects when 'low-SD' measurements such as wall thickness and the wall thickness: internal radius ratio are employed. The estimated prevalence of LVH and remodelling is still greater with multivariate discriminant function analysis, with which it is found in about 70% of hypertensives. Overall, the data suggest that prevalence of LVH in established hypertension is high. The 30% of subjects reported to have LVH on the basis of LVMI measurements that are beyond the limits of the control group probably have the most severe changes. The inability to detect lesser grades of left ventricular remodelling reliably is due to the way LVMI is derived by echocardiography, rather than to intrinsic inaccuracies. It suggests that existing approaches should be supplemented by greater use of 'low-SD' variables

  18. Age-associated Pro-inflammatory Remodeling and Functional Phenotype in the Heart and Large Arteries

    PubMed Central

    Wang, Mingyi; Shah, Ajay M

    2015-01-01

    The aging population is increasing dramatically. Aging–associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal ventricular-arterial coupling, features that are often clinically silent and thus termed a silent syndrome. These age-related effects are the result of responses initiated by cardiovascular proinflammatory cells. Local proinflammatory signals are coupled between the heart and arteries due to common mechanical and humoral messengers within a closed circulating system. Thus, targeting proinflammatory signaling molecules would be a promising approach to improve age-associated suboptimal ventricular-arterial coupling, a major predisposing factor for the pathogenesis of clinical cardiovascular events such as heart failure. PMID:25665458

  19. The future of left ventricular assist devices

    PubMed Central

    2015-01-01

    The widespread acceptance of left ventricular assist device (LVAD) implantation in the treatment of heart failure has revolutionized the way end stage heart failure is treated. Advances in LVAD technology combined with a better understanding of patient selection has led to unparalleled survival as well as a reduction in the adverse event profile of these pumps. As our understanding of heart failure continues to grow, there is little doubt that LVADs will continue to play a pivotal role as a therapeutic option for those suffering from heart failure. PMID:26793340

  20. Redox regulation of vascular remodeling.

    PubMed

    Karimi Galougahi, Keyvan; Ashley, Euan A; Ali, Ziad A

    2016-01-01

    Vascular remodeling is a dynamic process of structural and functional changes in response to biochemical and biomechanical signals in a complex in vivo milieu. While inherently adaptive, dysregulation leads to maladaptive remodeling. Reactive oxygen species participate in homeostatic cell signaling in tightly regulated- and compartmentalized cellular circuits. It is well established that perturbations in oxidation-reduction (redox) homeostasis can lead to a state of oxidative-, and more recently, reductive stress. We provide an overview of the redox signaling in the vasculature and review the role of oxidative- and reductive stress in maladaptive vascular remodeling. Particular emphasis has been placed on essential processes that determine phenotype modulation, migration and fate of the main cell types in the vessel wall. Recent advances in systems biology and the translational opportunities they may provide to specifically target the redox pathways driving pathological vascular remodeling are discussed. PMID:26483132

  1. Plant cell remodeling by autophagy

    PubMed Central

    Kim, Jimi; Lee, Han Nim; Chung, Taijoon

    2014-01-01

    Plant seedlings are not photoautotrophs until they are equipped with photosynthetic machinery. Some plant cells are remodeled after being exposed to light, and a group of peroxisomal proteins are degraded during the remodeling. Autophagy was proposed as one of the mechanisms for the degradation of peroxisomal proteins. We recently showed that ATG7-dependent autophagy is partially responsible for the degradation of obsolete peroxisomal proteins during Arabidopsis seedling growth. PMID:24492493

  2. Aerobic Training after Myocardial Infarction: Remodeling Evaluated by Cardiac Magnetic Resonance

    PubMed Central

    Izeli, Nataly Lino; dos Santos, Aurélia Juliana; Crescêncio, Júlio César; Gonçalves, Ana Clara Campagnolo Real; Papa, Valéria; Marques, Fabiana; Pazin-Filho, Antônio; Gallo-Júnior, Lourenço; Schmidt, André

    2016-01-01

    Background Numerous studies show the benefits of exercise training after myocardial infarction (MI). Nevertheless, the effects on function and remodeling are still controversial. Objectives To evaluate, in patients after (MI), the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR). Methods 26 male patients, 52.9 ± 7.9 years, after a first MI, were assigned to groups: trained group (TG), 18; and control group (CG), 8. The TG performed supervised aerobic exercise on treadmill twice a week, and unsupervised sessions on 2 additional days per week, for at least 3 months. Laboratory tests, anthropometric measurements, resting heart rate (HR), exercise test, and CMR were conducted at baseline and follow-up. Results The TG showed a 10.8% reduction in fasting blood glucose (p = 0.01), and a 7.3-bpm reduction in resting HR in both sitting and supine positions (p < 0.0001). There was an increase in oxygen uptake only in the TG (35.4 ± 8.1 to 49.1 ± 9.6 mL/kg/min, p < 0.0001). There was a statistically significant decrease in the TG left ventricular mass (LVmass) (128.7 ± 38.9 to 117.2 ± 27.2 g, p = 0.0032). There were no statistically significant changes in the values of left ventricular end-diastolic volume (LVEDV) and ejection fraction in the groups. The LVmass/EDV ratio demonstrated a statistically significant positive remodeling in the TG (p = 0.015). Conclusions Aerobic exercise of moderate intensity improved physical capacity and other cardiovascular variables. A positive remodeling was identified in the TG, where a left ventricular diastolic dimension increase was associated with LVmass reduction. PMID:26959403

  3. Right Ventricular Myxoma.

    PubMed

    Vadivelmurugan, S; Senthamarai; Sakthimohan; Janarthanan; Balanayagam; Anand, Vijay; Venkateswaran, K J; Ramkumar; Selvaraj

    2015-10-01

    We report a case of 30 year female who presented with complaints of intermittent chest pain and breathlessness for 8 months, Diagnosed to have right ventricular mass protruding into main pulmonary artery during each systole. The mass was completely excised. Histopathological examination showed myxoma. PMID:27608701

  4. Relationship between self-reported residential indoor remodeling and semen quality: a case-control study

    PubMed Central

    Miao, Mao-Hua; Li, Zheng; Li, De-Kun; Yan, Bei; Liang, Hong; Zhi, Er-Lei; Du, Hong-Wei; Yuan, Wei

    2015-01-01

    The present study examined the association between residential indoor remodeling and poor semen quality. Sperm donors aged 18–45 years old were recruited in Shanghai, China. Semen specimens were collected and analyzed. An in-person interview was conducted to obtain information on the history of indoor remodeling and potential confounders. A total of 70 participants with abnormal semen quality (case group) and 68 controls were examined. A total of 20 subjects reported indoor remodeling in the recent 24 months, and among them 17 subjects reported indoor remodeling in the recent 12 months. Compared with participants with no history of indoor remodeling, participants with a history of indoor remodeling in the recent 24 months were more than three times as likely to have poor sperm quality (adjusted odds ratio = 3.8, 95% confidence interval: 1.3–12.0) after controlling for potential confounders. The association was strengthened when the analysis was restricted to those who had indoor remodeling in the recent 12 months. Our findings provide preliminary evidence that indoor remodeling has an adverse effect on semen quality. PMID:25432500

  5. Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance

    PubMed Central

    Kim, Jiwon; Medicherla, Chaitanya B.; Ma, Claudia L.; Feher, Attila; Kukar, Nina; Geevarghese, Alexi; Goyal, Parag; Horn, Evelyn; Devereux, Richard B.; Weinsaft, Jonathan W.

    2016-01-01

    Background Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. Methods and Results The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5±3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34±10 vs. 39±9%; p = 0.01) but similar LVEF (40±21 vs. 39±18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17±7 vs. 12±6 kPa; p<0.001) corresponding to increased RV end-systolic volume (143±79 vs. 110±36 ml; p = 0.006), myocardial mass (60±21 vs. 53±17 gm; p = 0.04), and PASP (52±18 vs. 41±18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04–1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14–1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69–1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001). Conclusion Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling. PMID:26799498

  6. Noninvasive mapping of ventricular arrhythmias.

    PubMed

    Shah, Ashok J; Lim, Han S; Yamashita, Seigo; Zellerhoff, Stephan; Berte, Benjamin; Mahida, Saagar; Hooks, Darren; Aljefairi, Nora; Derval, Nicolas; Denis, Arnaud; Sacher, Frédéric; Jais, Pierre; Dubois, Rémi; Hocini, Meleze; Haissaguerre, Michel

    2015-03-01

    Several decades of research has led to the development of a 252-lead electrocardiogram-based three-dimensional imaging modality to refine noninvasive diagnosis and improve the management of heart rhythm disorders. This article reviews the clinical potential of this noninvasive mapping technique in identifying the sources of electrical disorders and guiding the catheter ablation of ventricular arrhythmias (premature ventricular beats and ventricular tachycardia). The article also briefly refers to the noninvasive electrical imaging of the arrhythmogenic ventricular substrate based on the electrophysiologic characteristics of postinfarction ventricular myocardium. PMID:25784026

  7. Ventricular Tachycardias: Characteristics and Management.

    PubMed

    Baldzizhar, Aksana; Manuylova, Ekaterina; Marchenko, Roman; Kryvalap, Yury; Carey, Mary G

    2016-09-01

    Ventricular tachycardias include ventricular tachycardia, ventricular fibrillation, and torsades de pointes; although these rhythms may be benign and asymptomatic, others may be life threatening and lead to increased morbidity and mortality. To optimize patient outcomes, ventricular tachycardias need to be rapidly diagnosed and managed, and often the electrocardiogram (ECG) is the first and only manifestation of a cardiac defect. Understanding of the initial electrocardiographic pattern and subsequent changes can lead to early intervention and an improved outcome. This article describes mechanisms, ECG characteristics, and management of ventricular tachycardias. PMID:27484660

  8. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

    NASA Astrophysics Data System (ADS)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

    2004-04-01

    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  9. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  10. Pathophysiology of LV Remodeling in Survivors of STEMI

    PubMed Central

    Carrick, David; Haig, Caroline; Rauhalammi, Sam; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Lindsay, Mitchell; Watkins, Stuart; Hood, Stuart; Davie, Andrew; Mahrous, Ahmed; Sattar, Naveed; Welsh, Paul; Tzemos, Niko; Radjenovic, Aleksandra; Ford, Ian; Oldroyd, Keith G.; Berry, Colin

    2015-01-01

    Objectives The aim of this study was to investigate the clinical significance of native T1 values in remote myocardium in survivors of acute ST-segment elevation myocardial infarction (STEMI). Background The pathophysiology and prognostic significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) reveals myocardial function and pathology. Native T1 (relaxation time in ms) is a fundamental magnetic resonance tissue property determined by water content and cellularity. Results A total of 300 STEMI patients (mean age 59 years; 74% male) gave informed consent. A total of 288 STEMI patients had evaluable native T1 CMR, and 267 patients (91%) had follow-up CMR at 6 months. Health outcome information was obtained for all of the participants (median follow-up 845 days). Infarct size was 18 ± 13% of left ventricular (LV) mass. Two days post-STEMI, native T1 was lower in remote myocardium than in the infarct zone (961 ± 25 ms vs. 1,097 ± 52 ms; p < 0.01). In multivariable regression, incomplete ST-segment resolution was associated with myocardial remote zone native T1 (regression coefficient 9.42; 95% confidence interval [CI]: 2.37 to 16.47; p = 0.009), as were the log of the admission C-reactive protein concentration (3.01; 95% CI: 0.016 to 5.85; p = 0.038) and the peak monocyte count (10.20; 95% CI: 0.74 to 19.67; p = 0.035). Remote T1 at baseline was associated with log N-terminal pro–B-type natriuretic peptide at 6 months (0.01; 95% CI: 0.00 to 0.02; p = 0.002; n = 151) and the change in LV end-diastolic volume from baseline to 6 months (0.13; 95% CI: 0.01 to 0.24; p = 0.035). Remote zone native T1 was independently associated with post-discharge major adverse cardiac events (n = 20 events; hazard ratio: 1.016; 95% CI: 1.000 to 1.032; p = 0.048) and all-cause death or heart failure hospitalization (n = 30 events during admission and post-discharge; hazard ratio: 1.014; 95% CI: 1.000 to 1.028; p = 0

  11. Special Situations in Pulmonary Hypertension: Pregnancy and Right Ventricular Failure.

    PubMed

    Svetlichnaya, Jana; Janmohammed, Munir; De Marco, Teresa

    2016-08-01

    Despite rapid advances in medical therapy, pregnancy and right ventricular (RV) failure predicts a poor prognosis in patients with pulmonary arterial hypertension. Evidence-based therapy for pulmonary arterial hypertension should be initiated early in the disease course to decrease RV wall stress and prevent RV remodeling and fibrosis. In patients with acutely decompensated RV failure, an aggressive and multifaceted approach must be used; a thorough search for triggering factors for the decompensation is a key part of the successful management strategy. Patients with refractory RV failure who are not candidates for surgical intervention should be referred to palliative care to maximize quality of life and symptom relief. PMID:27443142

  12. [Pathophysiology of left ventricular hypertrophy in arterial hypertension].

    PubMed

    Vallotton, M B; Braconi-Quintaje, S; Lang, U

    1997-02-11

    The role of left ventricular hypertrophy as an independent risk factor for subsequent cardio-vascular events is well established, therefore the authors, in this brief review, describe the endocrine function of the heart and the role played by various factors, including hormones, in the development of cardiac remodeling during the course of hypertension. They then outline the present state of our knowledge concerning transmembrane signaling in the cardiomyocyte in response to an activation of specific receptors for vasoactive hormones of the renin-angiotensin II-aldosterone system. PMID:9139339

  13. Intracoronary infusion of autologous mononuclear cells from bone marrow or G-CSF mobilised apheresis product may not improve remodelling, contractile function, perfusion or infarct size in a swine model of large myocardial infarction

    PubMed Central

    de Silva, Ranil; Raval, Amish N.; Hadi, Mohiuddin; Gildea, Karena M.; Bonifacino, Aylin C.; Yu, Zu-Xi; Yau, Yu Ying; Leitman, Susan F.; Bacharach, Stephen L.; Donahue, Robert E.; Read, Elizabeth J.; Lederman, Robert J.

    2008-01-01

    Background In a blinded, placebo controlled study, we investigated whether intracoronary infusion of autologous mononuclear cells from G-CSF mobilised apheresis product or bone marrow (BM) improved sensitive outcome measures in a swine model of large MI. Methods and Results Four days after LAD occlusion and reperfusion, cells from BM or apheresis product of saline (Placebo) or G-CSF injected animals were infused into the LAD. Large infarcts were created: baseline ejection fraction (EF) by MRI of 35.3 ± 8.5%, no difference between the Placebo, G-CSF and BM groups (p=0.16 by ANOVA). At 6 weeks EF fell to a similar degree in the Placebo, G-CSF and BM groups (−7.9±6.0%, −8.5±8.8% and −10.9±7.6%, p=0.78 by ANOVA). Left ventricular volumes and infarct size by MRI deteriorated similarly in all 3 groups. Quantitative PET demonstrated significant decline in FDG uptake rate in the LAD territory at follow-up, with no histological, angiographic or PET perfusion evidence of functional neovascularisation. Immunofluorescence failed to demonstrate transdifferentiation of infused cells. Conclusion Intracoronary infusion of mononuclear cells from either bone marrow or G-CSF mobilised apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size or perfusion in a swine model of large MI. PMID:18502738

  14. Polydatin Attenuates Hypoxic Pulmonary Hypertension and Reverses Remodeling through Protein Kinase C Mechanisms

    PubMed Central

    Miao, Qing; Shi, Xiao-Peng; Ye, Ming-Xiang; Zhang, Jin; Miao, Shan; Wang, Si-Wang; Li, Bo; Jiang, Xiu-Xiu; Zhang, Song; Hu, Nan; Li, Juan; Zhang, Jian

    2012-01-01

    Hypoxic pulmonary hypertension is a life-threatening emergency if untreated. Consistent pulmonary hypertension also leads to arteries and ventricular remodeling. The clinical therapeutic strategy for pulmonary hypertension and the corresponding remodeling mainly interacts with NO, angiotensin II (Ang II) and elevated endothelin (ET) targets. In the present study, we evaluated the effects of polydatin on hypoxia-induced pulmonary hypertension. It was observed that polydatin attenuated hypoxic pulmonary hypertension, reversed remodeling, and regulated NO, Ang II, ET contents in the serum and lung samples. However, forced activation of PKC signaling by its selective activator thymeleatoxin (THX) could abate the effects of polydatain. These results suggest that polydatin might be a promising candidate for hypoxic pulmonary treatment through interaction with PKC mechanisms. PMID:22837726

  15. Prevalence, Clinical Characteristics, and Outcomes Associated with Eccentric versus Concentric Left Ventricular Hypertrophy In Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Katz, Daniel H.; Beussink, Lauren; Sauer, Andrew J.; Freed, Benjamin H.; Burke, Michael A.; Shah, Sanjiv J.

    2013-01-01

    While concentric remodeling (CR) and concentric hypertrophy (CH) are common forms of left ventricular (LV) remodeling in heart failure with preserved ejection fraction (HFpEF), eccentric hypertrophy (EH) can also occur in these patients. However, clinical characteristics and outcomes of EH have not been well described in HFpEF. We prospectively studied 402 patients with HFpEF, divided into 4 groups based on LV structure: normal geometry (no LV hypertrophy [LVH] and relative wall thickness [RWT] < 0.42); CR (no LVH and RWT > 0.42); CH (LVH and RWT > 0.42); and EH (LVH and RWT < 0.42). We compared clinical, laboratory, echocardiographic, invasive hemodynamic, and outcome data among groups. Of 402 patients, 48 (12%) had EH. Compared to CH, patients with EH had lower systolic blood pressure and less renal impairment despite similar rates of hypertension. After adjustment for covariates, EH was associated with reduced LV contractility compared to CH (lower LVEF [β-coefficient = −3.2; 95% confidence interval (CI) −5.4, −1.1%] and ratio of systolic blood pressure to end-systolic volume [β-coefficient = −1.0; 95% CI −1.5, −0.5 mmHg/ml]). EH was also associated with increased LV compliance compared to CH (LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mmHg [EDV20] β-coefficient = 14.2;95% CI 9.4, 19.1 ml). Despite these differences, EH and CH had similarly elevated cardiac filling pressures and equivalent adverse outcomes. In conclusion, the presence of EH denotes a distinct subset of HFpEF that is pathophysiologically similar to HF with reduced EF (HFrEF), and may benefit from HFrEF therapy. PMID:23810323

  16. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures. PMID:18375722

  17. Bridge to Removal: A Paradigm Shift for Left Ventricular Assist Device Therapy

    PubMed Central

    Selzman, Craig H.; Madden, Jesse L.; Healy, Aaron H.; McKellar, Stephen H.; Koliopoulou, Antigone; Stehlik, Josef; Drakos, Stavros G.

    2014-01-01

    Ventricular assist devices have become standard therapy for patients with advanced heart failure either as a bridge to transplantation or destination therapy. Despite the functional and biologic evidence of reverse cardiac remodeling, few patients actually proceed to myocardial recovery, and even fewer to the point of having their device explanted. An enhanced understanding of the biology and care of the mechanically supported patient has redirected focus on the possibility of using ventricular assist devices as a bridge to myocardial recovery and removal. Herein, we review the current issues and approaches to transforming myocardial recovery to a practical reality. PMID:25442985

  18. Left Ventricular Non-compaction with Multiple Ventricular Septal Defects

    PubMed Central

    Moorthy, Nagaraja; Jain, Sandeep; Neyaz, Zafar; Kumar, Sunil; Goel, Pravin K.

    2015-01-01

    Left ventricular non-compaction (LVNC) is a congenital cardiomyopathy characterized by deep ventricular trabeculations thought to be due to an arrest of myocardial morphogenesis. Integration of various cardiac imaging modalities such as echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging help in the diagnosis of this rare clinical entity. We describe a child with rare variant of LVNC with predominant involvement of interventricular septum resulting in multiple ventricular septal defects. PMID:27326350

  19. ST-elevation myocardial infarction with reduced left ventricular ejection fraction: Insights into persisting left ventricular dysfunction. A pPCI-registry analysis.

    PubMed

    Stolfo, Davide; Cinquetti, Martino; Merlo, Marco; Santangelo, Sara; Barbati, Giulia; Alonge, Marco; Vitrella, Giancarlo; Rakar, Serena; Salvi, Alessandro; Perkan, Andrea; Sinagra, Gianfranco

    2016-07-15

    Primary percutaneous coronary intervention (pPCI) largely reduced the rate of left ventricular (LV) dysfunction after ST-segment elevation acute myocardial infarction (STEMI). Though LV recovery begins early following revascularization, the optimal timing for re-assessment of LV function is still unclear. We sought to assess the proportion and timing of LV recovery in STEMI patients presenting with LV dysfunction treated by pPCI and to identify possible early predictors of adverse LV remodeling. STEMI patients with LV ejection fraction (LVEF ≤40%) at presentation treated by pPCI from 2007 to 2013 were included whether they had an available 3-step LVEF assessment (<24h post-pPCI, discharge and follow-up). Primary endpoint was LVEF ≤35% at follow-up. At a median time of 3months, 43 out of 154 patients (28%) had LVEF ≤35%. In patients with persistent LV dysfunction, LVEF was lower at admission and increased less during hospitalization (from 31±6 to 35±4% Vs 35±5 to 43±8% for patients with 3-months LVEF >35%, p<0.001). Independent predictors of 3-months LVEF ≤35% were creatinine at admission, peak troponin I and LVEF. Of note, LVEF re-assessment at discharge (median time 6days, IQR 4-9) showed an increased accuracy to predict 3-months LV dysfunction compared to LVEF at admission (AUC 0.80, 95% CI 0.72-0.88 vs AUC 0.69, 95% CI 0.58-0.79 respectively, p=0.03). In most of patients presenting with STEMI and LV dysfunction, a significant LV recovery can be observed early following pPCI. LVEF measurement at discharge indeed emerged as the best indicator of late persistence of severe LV dysfunction. PMID:27128558

  20. Anger and ventricular arrhythmias

    PubMed Central

    Lampert, Rachel

    2011-01-01

    Purpose of review Although anecdotal evidence has long suggested links between emotion and ventricular arrhythmia, more recent studies have prospectively demonstrated the arrhythmogenic effects of anger, as well as mechanisms underlying these effects. Recent findings Epidemiological studies reveal that psychological stress increases sudden death, as well as arrhythmias, in patients with implantable cardioverter-defibrillators, in populations during emotionally devastating disasters such as earthquake or war. Diary-based studies confirm that anger and other negative emotions can trigger potentially lethal ventricular arrhythmias. Anger alters electrophysiological properties of the myocardium, including T-wave alternans, a measure of heterogeneity of repolarization, suggesting one mechanistic link between emotion and arrhythmia. Pilot studies of behavioral interventions have shown promise in decreasing arrhythmias in patients with implantable cardioverter-defibrillators. Summary Anger and other strong emotions can trigger polymorphic, potentially life-threatening ventricular arrhythmias in vulnerable patients. Through autonomic changes including increased sympathetic activity and vagal withdrawal, anger leads to increases in heterogeneity of repolarization as measured by T-wave alternans, known to be associated with arrhythmogenesis, as well as increasing inducibility of arrhythmia. Further delineation of mechanisms linking anger and arrhythmia, and of approaches to decrease the detrimental effects of anger and other negative emotions on arrhythmogenesis, are important areas of future investigation. PMID:19864944

  1. Abnormal Ca2+ Cycling in Failing Ventricular Myocytes: Role of NOS1-Mediated Nitroso-Redox Balance

    PubMed Central

    Houser, Steven R.

    2014-01-01

    Abstract Significance: Heart failure (HF) results from poor heart function and is the leading cause of death in Western society. Abnormalities of Ca2+ handling at the level of the ventricular myocyte are largely responsible for much of the poor heart function. Recent Advances: Although studies have unraveled numerous mechanisms for the abnormal Ca2+ handling, investigations over the past decade have indicated that much of the contractile dysfunction and adverse remodeling that occurs in HF involves oxidative stress. Critical Issues: Regrettably, antioxidant therapy has been an immense disappointment in clinical trials. Thus, redox signaling is being reassessed to elucidate why antioxidants failed to treat HF. Future Directions: A recently identified aspect of redox signaling (specifically the superoxide anion radical) is its interaction with nitric oxide, known as the nitroso-redox balance. There is a large nitroso-redox imbalance with HF, and we suggest that correcting this imbalance may be able to restore myocyte contraction and improve heart function. Antioxid. Redox Signal. 21, 2044–2059. PMID:24801117

  2. Fat in the ventricular septum

    PubMed Central

    Donaldson, Erin E.; Ko, Jong Mi; Kuiper, Johannes J.; Chamogeorgakis, Themistokles

    2014-01-01

    Described herein is a 68-year-old man who underwent cardiac transplantation for severe chronic heart failure resulting from ischemic cardiomyopathy. Examination of the excised heart showed not only extensive left ventricular scarring but also a huge collection of adipose tissue in the subepicardial region and surprisingly also in the ventricular septum. The finding of fat in the ventricular septum is extremely rare and prompted this report. PMID:24982572

  3. Capecitabine-induced ventricular fibrillation arrest: Possible Kounis syndrome.

    PubMed

    Kido, Kazuhiko; Adams, Val R; Morehead, Richard S; Flannery, Alexander H

    2016-04-01

    We report the case of capecitabine-induced ventricular fibrillation arrest, possibly secondary to type I Kounis syndrome. A 47-year-old man with a history of T3N1 moderately differentiated adenocarcinoma of the colon, status-post sigmoid resection, was started on adjuvant capecitabine approximately five months prior to presentation of cardiac arrest secondary to ventricular fibrillation. An electrocardiogram (EKG) revealed ST segment elevation on the lateral leads and the patient was taken emergently to the cardiac catheterization laboratory. The catheterization revealed no angiographically significant stenosis and coronary artery disease was ruled out. After ruling out other causes of cardiac arrest, the working diagnosis was capecitabine-induced ventricular fibrillation arrest. As such, an inflammatory work up was sent to evaluate for the possibility of a capecitabine hypersensitivity, or Kounis syndrome, and is the first documented report in the literature to do so when evaluating Kounis syndrome. Immunoglobulin E (IgE), tryptase, and C-reactive protein were normal but histamine, interleukin (IL)-6, and IL-10 were elevated. Histamine elevation supports the suspicion that our patient had type I Kounis syndrome. Naranjo adverse drug reaction probability scale indicates a probable adverse effect due to capecitabine with seven points. A case of capecitabine-induced ventricular fibrillation arrest is reported, with a potential for type 1 Kounis syndrome as an underlying pathology supported by immunologic work up. PMID:25870182

  4. Apocynin improving cardiac remodeling in chronic renal failure disease is associated with up-regulation of epoxyeicosatrienoic acids

    PubMed Central

    Chen, Jie; Cai, Qingqing; Wang, Jingfeng; Huang, Hui

    2015-01-01

    Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight /body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions. PMID:26322503

  5. Apocynin improving cardiac remodeling in chronic renal failure disease is associated with up-regulation of epoxyeicosatrienoic acids.

    PubMed

    Zhang, Kun; Liu, Yu; Liu, Xiaoqiang; Chen, Jie; Cai, Qingqing; Wang, Jingfeng; Huang, Hui

    2015-09-22

    Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight / body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions. PMID:26322503

  6. Signaling effectors underlying pathologic growth and remodeling of the heart

    PubMed Central

    van Berlo, Jop H.; Maillet, Marjorie; Molkentin, Jeffery D.

    2013-01-01

    Cardiovascular disease is the number one cause of mortality in the Western world. The heart responds to many cardiopathological conditions with hypertrophic growth by enlarging individual myocytes to augment cardiac pump function and decrease ventricular wall tension. Initially, such cardiac hypertrophic growth is often compensatory, but as time progresses these changes become maladaptive. Cardiac hypertrophy is the strongest predictor for the development of heart failure, arrhythmia, and sudden death. Here we discuss therapeutic avenues emerging from molecular and genetic studies of cardiovascular disease in animal models. The majority of these are based on intracellular signaling pathways considered central to pathologic cardiac remodeling and hypertrophy, which then leads to heart failure. We focus our discussion on selected therapeutic targets that have more recently emerged and have a tangible translational potential given the available pharmacologic agents that could be readily evaluated in human clinical trials. PMID:23281408

  7. The left ventricle as a mechanical engine: from Leonardo da Vinci to the echocardiographic assessment of peak power output-to-left ventricular mass.

    PubMed

    Dini, Frank L; Guarini, Giacinta; Ballo, Piercarlo; Carluccio, Erberto; Maiello, Maria; Capozza, Paola; Innelli, Pasquale; Rosa, Gian M; Palmiero, Pasquale; Galderisi, Maurizio; Razzolini, Renato; Nodari, Savina

    2013-03-01

    The interpretation of the heart as a mechanical engine dates back to the teachings of Leonardo da Vinci, who was the first to apply the laws of mechanics to the function of the heart. Similar to any mechanical engine, whose performance is proportional to the power generated with respect to weight, the left ventricle can be viewed as a power generator whose performance can be related to left ventricular mass. Stress echocardiography may provide valuable information on the relationship between cardiac performance and recruited left ventricular mass that may be used in distinguishing between adaptive and maladaptive left ventricular remodeling. Peak power output-to-mass, obtained during exercise or pharmacological stress echocardiography, is a measure that reflects the number of watts that are developed by 100 g of left ventricular mass under maximal stimulation. Power output-to-mass may be calculated as left ventricular power output per 100 g of left ventricular mass: 100× left ventricular power output divided by left ventricular mass (W/100 g). A simplified formula to calculate power output-to-mass is as follows: 0.222 × cardiac output (l/min) × mean blood pressure (mmHg)/left ventricular mass (g). When the integrity of myocardial structure is compromised, a mismatch becomes apparent between maximal cardiac power output and left ventricular mass; when this occurs, a reduction of the peak power output-to-mass index is observed. PMID:21934524

  8. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    SciTech Connect

    Ostrup, Olga; Hyttel, Poul; Klaerke, Dan A.; Collas, Philippe

    2011-09-02

    Highlights: {yields} Xenopus egg extract remodels nuclei and alter cell growth characteristics. {yields} Ribosomal genes are reprogrammed within 6 h after extract exposure. {yields} rDNA reprogramming involves promoter targeting of SNF2H remodeling complex. {yields} Xenopus egg extract does not initiate stress-related response in somatic cells. {yields} Aza-cytidine elicits a stress-induced response in reprogrammed cells. -- Abstract: Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression. This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation of various reprogramming methods.

  9. Cardiac protein synthesis and degradation during thyroxine-induced left ventricular hypertrophy.

    PubMed

    Parmacek, M S; Magid, N M; Lesch, M; Decker, R S; Samarel, A M

    1986-11-01

    Assessment of cardiac protein metabolism in thyroxine-induced left ventricular hypertrophy requires measurements of both protein synthesis and degradation. In vivo protein degradative rates can best be measured as the difference between rates of protein synthesis and growth. Accordingly, rates of left ventricular protein accumulation were determined in growing rabbits, and in animals administered intravenous L-thyroxine (200 micrograms X kg-1 X day-1) for up to 15 days. Left ventricular protein fractional synthetic rates in euthyroid and thyroxine-treated rabbits were measured by continuous infusion of [3H]leucine (200 mu Ci/h X 6 h), and results converted to milligrams protein synthesized and degraded per day. Thyroxine administration produced left ventricular hypertrophy by increasing the rate of total protein synthesis (35.7 +/- 2.0, 71.0 +/- 7.0, and 62.6 +/- 4.0 mg of left ventricular protein synthesized per day for 0-, 3-, and 9-day, thyroxine-treated rabbits, respectively). However, the increased rate of total protein synthesis was greater than the measured rate of total protein accumulation (8.1 vs. 15.9 mg protein/day for euthyroid and thyroxine-treated animals), indicating that left ventricular protein degradative rates were increased as well. These studies indicate that accelerated proteolysis may be important in the molecular and architectural remodeling of the rapidly hypertrophying heart during thyrotoxicosis. PMID:2946236

  10. Ventricular longitudinal function is associated with microvascular obstruction and intramyocardial haemorrhage

    PubMed Central

    Foley, James R J; Musa, Tarique Al; Ripley, David P; Swoboda, Peter P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Greenwood, John P; Plein, Sven

    2016-01-01

    Background Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are associated with adverse prognosis, independently of infarct size after reperfused ST-elevation myocardial infarction (STEMI). Mitral annular plane systolic excursion (MAPSE) is a well-established parameter of longitudinal function on echocardiography. Objective We aimed to investigate how acute MAPSE, assessed by a four-chamber cine-cardiovascular MR (CMR), is associated with MVO, IMH and convalescent left ventricular (LV) remodelling. Methods 54 consecutive patients underwent CMR at 3T (Intera CV, Philips Healthcare, Best, The Netherlands) within 3 days of reperfused STEMI. Cine, T2-weighted, T2* and late gadolinium enhancement (LGE) imaging were performed. Infarct and MVO extent were measured from LGE images. The presence of IMH was investigated by combined analysis of T2w and T2* images. Averaged-MAPSE (medial-MAPSE+lateral-MAPSE/2) was calculated from 4-chamber cine imaging. Results 44 patients completed the baseline scan and 38 patients completed 3-month scans. 26 (59%) patients had MVO and 25 (57%) patients had IMH. Presence of MVO and IMH were associated with lower averaged-MAPSE (11.7±0.4 mm vs 9.3±0.3 mm; p<0.001 and 11.8±0.4 mm vs 9.2±0.3 mm; p<0.001, respectively). IMH (β=−0.655, p<0.001) and MVO (β=−0.567, p<0.001) demonstrated a stronger correlation to MAPSE than other demographic and infarct characteristics. MAPSE ≤10.6 mm demonstrated 89% sensitivity and 72% specificity for the detection of MVO and 92% sensitivity and 74% specificity for IMH. LV remodelling in convalescence was not associated with MAPSE (AUC 0.62, 95% CI 0.44 to 0.77, p=0.22). Conclusions Postreperfused STEMI, LV longitudinal function assessed by MAPSE can independently predict the presence of MVO and IMH. PMID:27175286

  11. Amiodarone-induced hypothyroidism and other adverse effects.

    PubMed

    Mosher, Mary C

    2011-01-01

    Amiodarone is a class III antiarrhythmic agent that is frequently prescribed today for the treatment of ventricular and atrial arrhythmias. Amiodarone has many adverse effects, and one of them is thyroid dysfunction. Advanced practice and staff nurses need to be vigilant, recognizing early signs and symptoms of thyroid dysfunction to prevent adverse drug reactions. Often, the signs and symptoms of amiodarone-induced hypothyroidism are overlooked because of the complexity of the patient's condition. The purpose of this article was to review a case study, present differential diagnoses and testing, discuss risk factors associated with amiodarone-induced hypothyroidism, discuss its pathogenesis, and review clinical management. PMID:21307683

  12. Frontiers in growth and remodeling.

    PubMed

    Menzel, Andreas; Kuhl, Ellen

    2012-06-01

    Unlike common engineering materials, living matter can autonomously respond to environmental changes. Living structures can grow stronger, weaker, larger, or smaller within months, weeks, or days as a result of a continuous microstructural turnover and renewal. Hard tissues can adapt by increasing their density and grow strong. Soft tissues can adapt by increasing their volume and grow large. For more than three decades, the mechanics community has actively contributed to understand the phenomena of growth and remodeling from a mechanistic point of view. However, to date, there is no single, unified characterization of growth, which is equally accepted by all scientists in the field. Here we shed light on the continuum modeling of growth and remodeling of living matter, and give a comprehensive overview of historical developments and trends. We provide a state-of-the-art review of current research highlights, and discuss challenges and potential future directions. Using the example of volumetric growth, we illustrate how we can establish and utilize growth theories to characterize the functional adaptation of soft living matter. We anticipate this review to be the starting point for critical discussions and future research in growth and remodeling, with a potential impact on life science and medicine. PMID:22919118

  13. Frontiers in growth and remodeling

    PubMed Central

    Menzel, Andreas; Kuhl, Ellen

    2012-01-01

    Unlike common engineering materials, living matter can autonomously respond to environmental changes. Living structures can grow stronger, weaker, larger, or smaller within months, weeks, or days as a result of a continuous microstructural turnover and renewal. Hard tissues can adapt by increasing their density and grow strong. Soft tissues can adapt by increasing their volume and grow large. For more than three decades, the mechanics community has actively contributed to understand the phenomena of growth and remodeling from a mechanistic point of view. However, to date, there is no single, unified characterization of growth, which is equally accepted by all scientists in the field. Here we shed light on the continuum modeling of growth and remodeling of living matter, and give a comprehensive overview of historical developments and trends. We provide a state-of-the-art review of current research highlights, and discuss challenges and potential future directions. Using the example of volumetric growth, we illustrate how we can establish and utilize growth theories to characterize the functional adaptation of soft living matter. We anticipate this review to be the starting point for critical discussions and future research in growth and remodeling, with a potential impact on life science and medicine. PMID:22919118

  14. Advances in understanding cartilage remodeling

    PubMed Central

    Li, Yefu; Xu, Lin

    2015-01-01

    Cartilage remodeling is currently among the most popular topics in osteoarthritis research. Remodeling includes removal of the existing cartilage and replacement by neo-cartilage. As a loss of balance between removal and replacement of articular cartilage develops (particularly, the rate of removal surpasses the rate of replacement), joints will begin to degrade. In the last few years, significant progress in molecular understanding of the cartilage remodeling process has been made. In this brief review, we focus on the discussion of some current “controversial” observations in articular cartilage degeneration: (1) the biological effect of transforming growth factor-beta 1 on developing and mature articular cartilages, (2) the question of whether aggrecanase 1 (ADAMTS4) and aggrecanase 2 (ADAMTS5) are key enzymes in articular cartilage destruction, and (3) chondrocytes versus chondron in the development of osteoarthritis. It is hoped that continued discussion and investigation will follow to better clarify these topics. Clarification will be critical for those in search of novel therapeutic targets for the treatment of osteoarthritis. PMID:26380073

  15. Right ventricular failure after left ventricular assist device implantation: the need for an implantable right ventricular assist device.

    PubMed

    Furukawa, Kojiro; Motomura, Tadashi; Nosé, Yukihiko

    2005-05-01

    Right ventricular failure after implantation of a left ventricular assist device is an unremitting problem. Consideration of portal circulation is important for reversing liver dysfunction and preventing multiple organ failure after left ventricular assist device implantation. To achieve these objectives, it is imperative to maintain the central venous pressure as low as possible. A more positive application of right ventricular assistance is recommended. Implantable pulsatile left ventricular assist devices cannot be used as a right ventricular assist device because of their structure and device size. To improve future prospects, it is necessary to develop an implantable right ventricular assist device based on a rotary blood pump. PMID:15854212

  16. Myofibroblast-mediated mechanisms of pathological remodelling of the heart.

    PubMed

    Weber, Karl T; Sun, Yao; Bhattacharya, Syamal K; Ahokas, Robert A; Gerling, Ivan C

    2013-01-01

    The syncytium of cardiomyocytes in the heart is tethered within a matrix composed principally of type I fibrillar collagen. The matrix has diverse mechanical functions that ensure the optimal contractile efficiency of this muscular pump. In the diseased heart, cardiomyocytes are lost to necrotic cell death, and phenotypically transformed fibroblast-like cells-termed 'myofibroblasts'-are activated to initiate a 'reparative' fibrosis. The structural integrity of the myocardium is preserved by this scar tissue, although at the expense of its remodelled architecture, which has increased tissue stiffness and propensity to arrhythmias. A persisting population of activated myofibroblasts turns this fibrous tissue into a living 'secretome' that generates angiotensin II and its type 1 receptor, and fibrogenic growth factors (such as transforming growth factor-β), all of which collectively act as a signal-transducer-effector signalling pathway to type I collagen synthesis and, therefore, fibrosis. Persistent myofibroblasts, and the resultant fibrous tissue they produce, cause progressive adverse myocardial remodelling, a pathological hallmark of the failing heart irrespective of its etiologic origin. Herein, we review relevant cellular, subcellular, and molecular mechanisms integral to cardiac fibrosis and consequent remodelling of atria and ventricles with a heterogeneity in cardiomyocyte size. Signalling pathways that antagonize collagen fibrillogenesis provide novel strategies for cardioprotection. PMID:23207731

  17. Electrical injury causing ventricular arrhythmias.

    PubMed Central

    Jensen, P J; Thomsen, P E; Bagger, J P; Nørgaard, A; Baandrup, U

    1987-01-01

    Dangerous or long lasting ventricular arrhythmias developed in three patients who had sustained an electrical injury in which current passed through the thorax. In all three cases there was a delay of 8-12 hours between the injury and the onset of symptoms. The ventricular arrhythmias were severe and long lasting. In two of the three patients, ventricular tachycardia or ventricular fibrillation or both occurred and in one patient ventricular parasystole developed. No enzymatic evidence of myocardial necrosis was found but the results of an endomyocardial biopsy carried out in two of the three patients showed focal myocardial fibrosis and increased numbers of Na, K-pumps. The two patients with ventricular tachycardia became symptom free after appropriate antiarrhythmic treatment and in the third patient ventricular parasystole disappeared spontaneously within two years. Patients sustaining electrical injury in which current passes through the thorax should be monitored electrocardiographically for at least 24 hours, and patients with unexpected arrhythmias should be questioned about previous electrical injury. Images Fig 2 PMID:3566986

  18. Epicardial ventricular tachycardia.

    PubMed

    Garan, Hasan

    2013-12-01

    In ventricular tachycardia (VT) arising in the myocardial tissue, the site of origin may be the endocardium, mid-myocardium or epicardium. The incidence of epicardial origin varies with the underlying heart disease, and is probably not more than 20% in ischemic heart disease and higher in non-ischemic cardiomyopathies. Percutaneous subxiphoid access to the pericardial space has enabled a non-surgical approach to catheter mapping and ablation of epicardial VT. Several algorithms are available for electrocardiographic recognition of epicardial origin. Idiopathic epicardial VTs are rare but may be curable by catheter ablation. The electrophysiologic principles guiding the mapping and ablation of epicardial VTs are similar to those used for endocardial VTs, but the biophysics of energy delivery may be different. Complications of the epicardial approach are also different from those of endocardial ablation, and specific precautions have to be taken to protect the coronary arteries and phrenic nerves and to avoid pericardial tamponade. PMID:24351953

  19. Arrhythmogenic right ventricular cardiomyopathy in a weimaraner

    PubMed Central

    Eason, Bryan D.; Leach, Stacey B.; Kuroki, Keiichi

    2015-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners. PMID:26483577

  20. Erythrocyte stiffness during morphological remodeling induced by carbon ion radiation.

    PubMed

    Zhang, Baoping; Liu, Bin; Zhang, Hong; Wang, Jizeng

    2014-01-01

    The adverse effect induced by carbon ion radiation (CIR) is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy) or X-rays (2, 4, 6, and 12 Gy) for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy). The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study provides a new

  1. Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation

    PubMed Central

    Zhang, Baoping; Liu, Bin; Zhang, Hong; Wang, Jizeng

    2014-01-01

    The adverse effect induced by carbon ion radiation (CIR) is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy) or X-rays (2, 4, 6, and 12 Gy) for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy). The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study provides a new

  2. Left ventricular pseudoaneurysm after perventricular ventricular septal defect device closure.

    PubMed

    Trezzi, Matteo; Kavarana, Minoo N; Hlavacek, Anthony M; Bradley, Scott M

    2014-03-01

    Perventricular ventricular septal defect (VSD) closure has been adopted as a therapeutic option for selected patients with muscular VSDs. This technique may combine some of the advantages of surgical and interventional techniques. Complication rates have been low: only one case of procedure-related left ventricular (LV) pseudoaneurysm has been documented. We report the surgical repair for a LV pseudoaneurysm after perventricular VSD device closure. PMID:24131474

  3. Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats

    PubMed Central

    Wang, Hao; Jessup, Jewell A.; Lin, Marina S.; Chagas, Clarissa; Lindsey, Sarah H.; Groban, Leanne

    2012-01-01

    Aims GPR30 is a novel oestrogen receptor expressed in various tissues, including the heart. We determined the role of GPR30 in the maintenance of left ventricular (LV) structure and diastolic function after the surgical loss of ovarian hormones in the female mRen2.Lewis rat, a model emulating the cardiac phenotype of the post-menopausal woman. Methods and results Bilateral oophorectomy (OVX) or sham surgery was performed in study rats; the selective GPR30 agonist, G-1 (50 µg/kg/day), or vehicle was given subcutaneously to OVX rats from 13–15 weeks of age. Similar to the cardiac phenotype of sham rats, G-1 preserved diastolic function and structure relative to vehicle-treated OVX littermates independent of changes in blood pressure. G-1 limited the OVX-induced increase in LV filling pressure, LV mass, wall thickness, interstitial collagen deposition, atrial natriuretic factor and brain natriuretic peptide mRNA levels, and cardiac NAD(P)H oxidase 4 (NOX4) expression. In vitro studies showed that G-1 inhibited angiotensin II-induced hypertrophy in H9c2 cardiomyocytes, evidenced by reductions in cell size, protein content per cell, and atrial natriuretic factor mRNA levels. The GPR30 antagonist, G15, inhibited the protective effects of both oestradiol and G-1 on this hypertrophy. Conclusion These data show that the GPR30 agonist G-1 mitigates the adverse effects of oestrogen loss on LV remodelling and the development of diastolic dysfunction in the study rats. This expands our knowledge of the sex-specific mechanisms underlying diastolic dysfunction and provides a potential therapeutic target for reducing the progression of this cardiovascular disease process in post-menopausal women. PMID:22328091

  4. Pulsatile Fluid Shear in Bone Remodeling

    NASA Technical Reports Server (NTRS)

    Frangos, John A.

    1997-01-01

    The objective of this investigation was to elucidate the sensitivity to transients in fluid shear stress in bone remodeling. Bone remodeling is clearly a function of the local mechanical environment which includes interstitial fluid flow. Traditionally, load-induced remodeling has been associated with low frequency (1-2 Hz) signals attributed to normal locomotion. McLeod and Rubin, however, demonstrated in vivo remodeling events associated with high frequency (15-30 Hz) loading. Likewise, other in vivo studies demonstrated that slowly applied strains did not trigger remodeling events. We therefore hypothesized that the mechanosensitive pathways which control bone maintenance and remodeling are differentially sensitive to varying rates of applied fluid shear stress.

  5. Effects of Phosphodiesterase Type 5 Inhibition on Systemic and Pulmonary Hemodynamics and Ventricular Function in Patients with Severe Symptomatic Aortic Stenosis

    PubMed Central

    Lindman, Brian R.; Zajarias, Alan; Madrazo, José A.; Shah, Jay; Gage, Brian F.; Novak, Eric; Johnson, Stephanie N.; Chakinala, Murali M.; Hohn, Tara A.; Saghir, Mohammed; Mann, Douglas L.

    2012-01-01

    Background Pressure overload due to aortic stenosis (AS) causes maladaptive ventricular and vascular remodeling that can lead to pulmonary hypertension, heart failure symptoms, and adverse outcomes. Retarding or reversing this maladaptive remodeling and its unfavorable hemodynamic consequences has potential to improve morbidity and mortality. Preclinical models of pressure overload have shown that phosphodiesterase type 5 (PDE5) inhibition is beneficial, however the use of PDE5 inhibitors in patients with AS is controversial because of concerns about vasodilation and hypotension. Methods and Results We evaluated the safety and hemodynamic response of 20 subjects with severe symptomatic AS (mean aortic valve area 0.7±0.2 cm2, ejection fraction 60±14%) who received a single oral dose of sildenafil (40mg or 80mg). Compared to baseline, after 60 minutes sildenafil reduced systemic (−12%, p<0.001) and pulmonary (−29%, p=0.002) vascular resistance, mean pulmonary artery (−25%, p<0.001) and wedge (−17%, p<0.001) pressure, and increased systemic (+13%, p<0.001) and pulmonary (+45%, p<0.001) vascular compliance and stroke volume index (+8%, p=0.01). These changes were not dose dependent. Sildenafil caused a modest decrease in mean systemic arterial pressure (−11%, p<0.001), but was well-tolerated with no episodes of symptomatic hypotension. Conclusions This study shows for the first time that a single dose of a PDE5 inhibitor is safe and well-tolerated in patients with severe AS and is associated with acute improvements in pulmonary and systemic hemodynamics resulting in biventricular unloading. These findings support the need for longer-term studies to evaluate the role of PDE5 inhibition as adjunctive medical therapy in patients with AS. PMID:22447809

  6. Facts about Ventricular Septal Defect

    MedlinePlus

    ... The size of the ventricular septal defect will influence what symptoms, if any, are present, and whether ... this image. Close Information For... Media Policy Makers Language: English Español (Spanish) File Formats Help: How do ...

  7. Adverse reactions to sulfites

    PubMed Central

    Yang, William H.; Purchase, Emerson C.R.

    1985-01-01

    Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products. PMID:4052897

  8. Multiscale Characterization of Impact of Infarct Size on Myocardial Remodeling in an Ovine Infarct Model

    PubMed Central

    Zhang, Pei; Li, Tielou; Griffith, Bartley P; Wu, Zhongjun J

    2015-01-01

    The surviving myocardium initially compensates the loss of injured myocardium after myocardial infarction (MI) and gradually becomes progressively dysfunctional. There have been limited studies of the influence of infarct size on temporal and spatial alteration of myocardium during progressive myocardial remodeling. MI with three infarct sizes (15%, 25% and 35% of left ventricular wall) was created in an ovine infarction model. The progressive LV remodeling over a 12 week period was studied. Echocardiography, sonomicrometry, histological and molecular analyses were carried out to evaluate cardiac function, regional tissue contractile function and structural remodeling, and regional cardiomycyte hypertrophy and calcium handling proteins. The 15%, 25% and 35% MI groups at 12 weeks after MI had normalized LV end diastole volumes of 1.4±0.2, 1.7±0.3 and 2.0±0.4 mL/Kg, normalized end systole volumes of 1.0±0.1, 1.0±0.2 and 1.3±0.3 mL/Kg and LV ejection fractions of 43%±3%, 42%±6% and 34%±4%, respectively. They all differed from a sham group (p<0.05). All the three MI groups exhibited larger wall areal expansion (remodeling strain), larger cardiomyocyte size and altered expression of calcium handing proteins in the adjacent myocardium compared to the remote counterpart from the infarct. Significant correlation was found between myocardiocyte size and remodeling strain in the adjacent zone. A comparative analysis among the three MI groups showed that a larger infarct size (35% vs. 15% MI) was associated with larger remodeling strain, impairment severity of cellular structure and composition, and regional contractile function at regional tissue level and LV cardiac function at organ level. PMID:26540290

  9. Remodeling of the heart (membrane proteins and collagen) in hypertensive cardiopathy.

    PubMed

    Sainte Beuve, C; Leclercq, C; Rannou, F; Oliviero, P; Mansier, P; Chevalier, B; Swynghedauw, B; Charlemagne, D

    1992-06-01

    The basis for impaired left ventricular function of hearts in moderate to severe stages of hypertrophy and congestive heart failure remains uncertain. At the cellular level, the mechanisms governing the movements of calcium in the myocardium are actually depressed and might at least in part account for the slowing of the maximum shortening velocity and the impaired relaxation. These alterations of membrane proteins seem particularly important in species where the slowing of Vmax cannot be a consequence of the myosin heavy chain shift. They lead to an unstable equilibrium of calcium homeostasis and to calcium overload in heart failure. On the other hand, the enhanced density and remodeling of collagen in the hypertrophied heart, which would depend on elevation in circulating aldosterone, impair myocardial stiffness with diastolic dysfunction and lead to altered pumping capacity of the heart. Disturbances of calcium metabolism and matrix collagen remodeling enhance early afterdepolarizations and arrhythmias. PMID:1385839

  10. Ventricular assist devices in pediatrics

    PubMed Central

    Fuchs, A; Netz, H

    2001-01-01

    The implantation of a mechanical circulatory device for end-stage ventricular failure is a possible therapeutic approach in adult and pediatric cardiac surgery and cardiology. The aim of this article is to present mechanical circulatory assist devices used in infants and children with special emphasis on extracorporeal membrane oxygenation, Berlin Heart assist device, centrifugal pump and Medos assist device. The success of long-term support with implantable ventricular assist devices in adults and children has led to their increasing use as a bridge to transplantation in patients with otherwise non-treatable left ventricular failure, by transforming a terminal phase heart condition into a treatable cardiopathy. Such therapy allows rehabilitation of patients before elective cardiac transplantation (by removing contraindications to transplantation mainly represented by organ impairment) or acting as a bridge to recovery of the native left ventricular function (depending on underlying cardiac disease). Treatment may also involve permanent device implantation when cardiac transplantation is contraindicated. Indications for the implantation of assisted circulation include all states of cardiac failure that are reversible within a variable period of time or that require heart transplantation. This article will address the current status of ventricular assist devices by examining historical aspects of its development, current technical issues and clinical features of pediatric ventricular assist devices, including indications and contraindications for support. PMID:22368605

  11. Dynamin, a membrane remodelling GTPase

    PubMed Central

    Ferguson, Shawn M.; De Camilli, Pietro

    2012-01-01

    Dynamin, the founding member of a family of dynamin-like GTPases (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live cell imaging, cell free-studies, X-ray crystallography and genetic studies in mice has greatly advanced our understanding of the mechanisms by which dynamin acts, its essential roles in cell physiology and the specific function of different dynamin isoforms. In addition, several connections between dynamin and human disease have also emerged that highlight specific contributions of this GTPase to the physiology of different tissues. PMID:22233676

  12. [Recurrent myocardial infarctions: specific changes in biomarkers and in myocardial remodeling (case-control study)].

    PubMed

    Volkova, E G; Malykhina, O P; Levashov, S Iu

    2007-01-01

    Basing on a case-control study (n=81) with the use of standard methods of myocardial infarction verification, examination of hemogram, troponin T, C-reactive protein, echocardiography data it was established that markers of myocardial infarction (troponin T level) and inflammation (C reactive protein level, lymphopenia) during recurrent infarctions are less pronounced than during first infarctions. Remodeling in recurrent infarctions had the following specific characteristics: increase of left ventricular end diastolic dimension, myocardial mass index, diastolic dysfunction and stroke volume with unchanged ejection fraction. PMID:18260891

  13. Cardiac remodeling in the mouse model of Marfan syndrome develops into two distinctive phenotypes.

    PubMed

    Tae, Hyun-Jin; Petrashevskaya, Natalia; Marshall, Shannon; Krawczyk, Melissa; Talan, Mark

    2016-01-15

    Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by mutations in fibrillin-1. Cardiac dysfunction in MFS has not been characterized halting the development of therapies of cardiac complication in MFS. We aimed to study the age-dependent cardiac remodeling in the mouse model of MFS FbnC1039G+/- mouse [Marfan heterozygous (HT) mouse] and its association with valvular regurgitation. Marfan HT mice of 2-4 mo demonstrated a mild hypertrophic cardiac remodeling with predominant decline of diastolic function and increased transforming growth factor-β canonical (p-SMAD2/3) and noncanonical (p-ERK1/2 and p-p38 MAPK) signaling and upregulation of hypertrophic markers natriuretic peptides atrium natriuretic peptide and brain natriuretic peptide. Among older HT mice (6-14 mo), cardiac remodeling was associated with two distinct phenotypes, manifesting either dilated or constricted left ventricular chamber. Dilatation of left ventricular chamber was accompanied by biochemical evidence of greater mechanical stress, including elevated ERK1/2 and p38 MAPK phosphorylation and higher brain natriuretic peptide expression. The aortic valve regurgitation was registered in 20% of the constricted group and 60% of the dilated group, whereas mitral insufficiency was observed in 40% of the constricted group and 100% of the dilated group. Cardiac dysfunction was not associated with the increase of interstitial fibrosis and nonmyocyte proliferation. In the mouse model fibrillin-1, haploinsufficiency results in the early onset of nonfibrotic hypertrophic cardiac remodeling and dysfunction, independently from valvular abnormalities. MFS heart is vulnerable to stress-induced cardiac dilatation in the face of valvular regurgitation, and stress-activated MAPK signals represent a potential target for cardiac management in MFS. PMID:26566724

  14. Conventional heart rate variability analysis of ambulatory electrocardiographic recordings fails to predict imminent ventricular fibrillation

    NASA Technical Reports Server (NTRS)

    Vybiral, T.; Glaeser, D. H.; Goldberger, A. L.; Rigney, D. R.; Hess, K. R.; Mietus, J.; Skinner, J. E.; Francis, M.; Pratt, C. M.

    1993-01-01

    OBJECTIVES. The purpose of this report was to study heart rate variability in Holter recordings of patients who experienced ventricular fibrillation during the recording. BACKGROUND. Decreased heart rate variability is recognized as a long-term predictor of overall and arrhythmic death after myocardial infarction. It was therefore postulated that heart rate variability would be lowest when measured immediately before ventricular fibrillation. METHODS. Conventional indexes of heart rate variability were calculated from Holter recordings of 24 patients with structural heart disease who had ventricular fibrillation during monitoring. The control group consisted of 19 patients with coronary artery disease, of comparable age and left ventricular ejection fraction, who had nonsustained ventricular tachycardia but no ventricular fibrillation. RESULTS. Heart rate variability did not differ between the two groups, and no consistent trends in heart rate variability were observed before ventricular fibrillation occurred. CONCLUSIONS. Although conventional heart rate variability is an independent long-term predictor of adverse outcome after myocardial infarction, its clinical utility as a short-term predictor of life-threatening arrhythmias remains to be elucidated.

  15. Ischemia-reperfusion injury leads to distinct temporal cardiac remodeling in normal versus diabetic mice.

    PubMed

    Eguchi, Megumi; Kim, Young Hwa; Kang, Keon Wook; Shim, Chi Young; Jang, Yangsoo; Dorval, Thierry; Kim, Kwang Joon; Sweeney, Gary

    2012-01-01

    Diabetes is associated with higher incidence of myocardial infarction (MI) and increased propensity for subsequent events post-MI. Here we conducted a temporal analysis of the influence of diabetes on cardiac dysfunction and remodeling after ischemia reperfusion (IR) injury in mice. Diabetes was induced using streptozotocin and IR performed by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for up to 42 days. We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV) in both control and diabetic mice. The longitudinal systolic and diastolic strain rate were altered after IR, but there were no significant differences between diabetic mice and controls. However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-((18)F)fluoro-D-glucose. Interestingly, after 24 hours reperfusion diabetic mice showed a reduced infarct size and less apoptosis indicated by TUNEL analysis in heart sections. This may be explained by increased levels of autophagy detected in diabetic mice hearts. Similar increases in IR-induced macrophage infiltration detected by CD68 staining indicated no change in inflammation between control and diabetic mice. Over time, control mice subjected to IR developed mild left ventricular dilation whereas diabetic mice exhibited a decrease in both end diastolic left ventricular volume and LVESV with a decreased intraventricular space and thicker left ventricular wall, indicating concentric hypertrophy. This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group. In summary, we demonstrate that diabetes principally influences distinct IR-induced chronic changes in cardiac

  16. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  17. Osteocyte-Driven Bone Remodeling

    PubMed Central

    Bellido, Teresita

    2013-01-01

    Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. The discovery that the inhibitor of bone formation sclerostin is primarily expressed in osteocytes in bone and it is downregulated by anabolic stimuli provided a mechanism by which osteocytes influence the activity of osteoblasts. Advances of the last few years provided experimental evidence demonstrating that osteocytes also participate in the recruitment of osteoclasts and the initiation of bone remodeling. Apoptotic osteocytes trigger yet to be identified signals that attract osteoclast precursors to specific areas of bone, which in turn differentiate to mature, bone resorbing osteoclasts. Osteocytes are also the source of molecules that regulate generation and activity of osteoclasts, such as OPG and RANKL; and genetic manipulations of the mouse genome leading to loss or gain of function, or to altered expression of either molecule in osteocytes, markedly affect bone resorption. This review highlights these investigations and discusses how the novel concept of osteocyte-driven bone resorption and formation impacts our understanding of the mechanisms by which current therapies control bone remodeling. PMID:24002178

  18. HDL biogenesis, remodeling, and catabolism.

    PubMed

    Zannis, Vassilis I; Fotakis, Panagiotis; Koukos, Georgios; Kardassis, Dimitris; Ehnholm, Christian; Jauhiainen, Matti; Chroni, Angeliki

    2015-01-01

    In this chapter, we review how HDL is generated, remodeled, and catabolized in plasma. We describe key features of the proteins that participate in these processes, emphasizing how mutations in apolipoprotein A-I (apoA-I) and the other proteins affect HDL metabolism. The biogenesis of HDL initially requires functional interaction of apoA-I with the ATP-binding cassette transporter A1 (ABCA1) and subsequently interactions of the lipidated apoA-I forms with lecithin/cholesterol acyltransferase (LCAT). Mutations in these proteins either prevent or impair the formation and possibly the functionality of HDL. Remodeling and catabolism of HDL is the result of interactions of HDL with cell receptors and other membrane and plasma proteins including hepatic lipase (HL), endothelial lipase (EL), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), apolipoprotein M (apoM), scavenger receptor class B type I (SR-BI), ATP-binding cassette transporter G1 (ABCG1), the F1 subunit of ATPase (Ecto F1-ATPase), and the cubulin/megalin receptor. Similarly to apoA-I, apolipoprotein E and apolipoprotein A-IV were shown to form discrete HDL particles containing these apolipoproteins which may have important but still unexplored functions. Furthermore, several plasma proteins were found associated with HDL and may modulate its biological functions. The effect of these proteins on the functionality of HDL is the topic of ongoing research. PMID:25522986

  19. Intracranial pressure and skull remodeling

    PubMed Central

    McCulley, Timothy J.; Jordan Piluek, W.; Chang, Jessica

    2014-01-01

    In this article we review bony changes resulting from alterations in intracranial pressure (ICP) and the implications for ophthalmologists and the patients for whom we care. Before addressing ophthalmic implications, we will begin with a brief overview of bone remodeling. Bony changes seen with chronic intracranial hypotension and hypertension will be discussed. The primary objective of this review was to bring attention to bony changes seen with chronic intracranial hypotension. Intracranial hypotension skull remodeling can result in enophthalmos. In advanced disease enophthalmos develops to a degree that is truly disfiguring. The most common finding for which subjects are referred is ocular surface disease, related to loss of contact between the eyelids and the cornea. Other abnormalities seen include abnormal ocular motility and optic atrophy. Recognition of such changes is important to allow for diagnosis and treatment prior to advanced clinical deterioration. Routine radiographic assessment of bony changes may allow for the identification of patient with abnormal ICP prior to the development of clinically significant disease. PMID:25859141

  20. Catheter Ablation of Polymorphic Ventricular Tachycardia and Ventricular Fibrillation

    PubMed Central

    Peichl, Petr

    2013-01-01

    Recently, catheter ablation (CA) has become a therapeutic option to target focal triggers of polymorphic ventricular tachycardia and ventricular fibrillation (VF) in the setting of electrical storm (ES). This strategy was first described in subjects without organic heart disease (i.e. idiopathic VF) and subsequently in other conditions, especially in patients with ischaemic heart disease. In the majority of cases, the triggering focus originates in the ventricular Purkinje system. In patients with Brugada syndrome, besides ablation of focal trigger in the right ventricular outflow tract, modification of a substrate in this region has been described to prevent recurrences of VF. In conclusion, CA appears to be a reasonable strategy for intractable cases of ES due to focally triggered polymorphic ventricular tachycardia and VF. Therefore, early transport of the patient into the experience centre for CA should be considered since the procedure could be in some cases life-saving. Therefore, the awareness of this entity and link to the nearest expert centre are important.

  1. An Analysis of the Residential Remodeling Occupation.

    ERIC Educational Resources Information Center

    Scruggs, Kenneth

    The general purpose of the occupational analysis is to provide workable, basic information dealing with the many and varied duties performed in the residential remodeling occupation. The analysis only briefly covers the many areas of residential remodeling. The document opens with a brief introduction followed by a job description. The bulk of the…

  2. Bone remodeling and silicon deficiency in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alveolar bone undergoes continuous remodeling to meet physiologic and functional demands. The aim of the present work was to evaluate histologically and histomorphometrically the effect of silicon deficiency on bone modeling and remodeling in the periodontal cortical plate. Two groups of weaning mal...

  3. Chromatin Remodelers: From Function to Dysfunction

    PubMed Central

    Längst, Gernot; Manelyte, Laura

    2015-01-01

    Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development. PMID:26075616

  4. Multiscale Simulation of Protein Mediated Membrane Remodeling

    PubMed Central

    Ayton, Gary S.; Voth, Gregory A.

    2009-01-01

    Proteins interacting with membranes can result in substantial membrane deformations and curvatures. This effect is known in its broadest terms as membrane remodeling. This review article will survey current multiscale simulation methodologies that have been employed to examine protein-mediated membrane remodeling. PMID:19922811

  5. New strategies for ventricular tachycardia and ventricular fibrillation ablation.

    PubMed

    Hooks, Darren A; Berte, Benjamin; Yamashita, Seigo; Mahida, Saagar; Sellal, Jean-Marc; Aljefairi, Nora; Frontera, Antonio; Derval, Nicolas; Denis, Arnaud; Hocini, Mélèze; Haïssaguerre, Michel; Jaïs, Pierre; Sacher, Frederic

    2015-03-01

    Patients with ventricular tachycardia (VT) and ventricular fibrillation (VF) and no reversible cause are difficult to treat. While implantable defibrillators prolong survival, many patients remain symptomatic due to device shocks and syncope. To address this, there have been recent advances in the catheter ablation of VT and VF. For example, non-invasive imaging has improved arrhythmia substrate characterisation, 3D catheter navigation tools have facilitated mapping of arrhythmia and substrate and ablation catheters have advanced in their ability to deliver effective lesions. However, the long-term success rates of ablation for VT and VF remain modest, with nearly half of treated patients developing recurrence within 2-3 years, and this drives the ongoing innovation in the field. This review focuses on the challenges particular to ablation of life-threatening ventricular arrhythmia, and the strategies that have been recently developed to improve procedural efficacy. Patient sub-groups that illustrate the use of new strategies are described. PMID:25666031

  6. Nucleosome dynamics during chromatin remodeling in vivo

    PubMed Central

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    ABSTRACT Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation. PMID:26933790

  7. Lipid Acyl Chain Remodeling in Yeast

    PubMed Central

    Renne, Mike F.; Bao, Xue; De Smet, Cedric H.; de Kroon, Anton I. P. M.

    2015-01-01

    Membrane lipid homeostasis is maintained by de novo synthesis, intracellular transport, remodeling, and degradation of lipid molecules. Glycerophospholipids, the most abundant structural component of eukaryotic membranes, are subject to acyl chain remodeling, which is defined as the post-synthetic process in which one or both acyl chains are exchanged. Here, we review studies addressing acyl chain remodeling of membrane glycerophospholipids in Saccharomyces cerevisiae, a model organism that has been successfully used to investigate lipid synthesis and its regulation. Experimental evidence for the occurrence of phospholipid acyl chain exchange in cardiolipin, phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine is summarized, including methods and tools that have been used for detecting remodeling. Progress in the identification of the enzymes involved is reported, and putative functions of acyl chain remodeling in yeast are discussed. PMID:26819558

  8. Nucleosome dynamics during chromatin remodeling in vivo.

    PubMed

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation. PMID:26933790

  9. Left ventricular geometry and white matter lesions in ischemic stroke patients.

    PubMed

    Butenaerts, Demian; Chrzanowska-Wasko, Joanna; Slowik, Agnieszka; Dziedzic, Tomasz

    2016-06-01

    Abnormal left ventricular (LV) geometry is associated with extracardiac organ damage in patients with hypertension. The aim of this study was to determine the relationship between LV geometry and white matter lesions (WMLs) in ischemic stroke patients. We retrospectively analyzed data from 155 patients (median age 62; 49.8% male) with mild ischemic stroke (median National Institutes of Health Stroke Scale score 4) who underwent brain magnetic resonance imaging and echocardiography. Patients were categorized into four groups: normal LV geometry, concentric remodeling, eccentric left ventricular hypertrophy (LVH) and concentric LVH. WMLs were graded using the Fazekas scale on fluid-attenuated inversion recovery images. Extensive WMLs were defined as a Fazekas score > 2. Extensive WMLs were more prevalent in patients with concentric LVH, eccentric LVH and concentric remodeling than in those with normal LV geometry. After adjusting for hypertension, age, diabetes mellitus, hypercholesterolemia, glomerular filtration rate and ischemic heart disease, patients with concentric remodeling [odds ratio (OR) 3.94, 95% confidence interval (CI) 1.26-12.31, p = 0.02] and those with concentric LVH (OR 3.69, 95% CI 1.24-10.95, p = 0.02), but not patients with eccentric LVH (OR 2.44, 95% CI 0.72-8.29, p = 0.15), had higher risk of extensive WMLs than patients with normal LV geometry. PMID:26581453

  10. Thyroid Hormone and Vascular Remodeling.

    PubMed

    Ichiki, Toshihiro

    2016-01-01

    Both hyperthyroidism and hypothyroidism affect the cardiovascular system. Hypothyroidism is known to be associated with enhanced atherosclerosis and ischemic heart diseases. The accelerated atherosclerosis in the hypothyroid state has been traditionally ascribed to atherogenic lipid profile, diastolic hypertension, and impaired endothelial function. However, recent studies indicate that thyroid hormone has direct anti-atherosclerotic effects, such as production of nitric oxide and suppression of smooth muscle cell proliferation. These data suggest that thyroid hormone inhibits atherogenesis through direct effects on the vasculature as well as modification of risk factors for atherosclerosis. This review summarizes the basic and clinical studies on the role of thyroid hormone in vascular remodeling. The possible application of thyroid hormone mimetics to the therapy of hypercholesterolemia and atherosclerosis is also discussed. PMID:26558400

  11. Calcium signalling remodelling and disease.

    PubMed

    Berridge, Michael J

    2012-04-01

    A wide range of Ca2+ signalling systems deliver the spatial and temporal Ca2+ signals necessary to control the specific functions of different cell types. Release of Ca2+ by InsP3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca2+ signals being set either too high or too low. Such subtle dysregulation of Ca2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease. PMID:22435804

  12. Left Ventricular Diastolic Dysfunction in Peritoneal Dialysis

    PubMed Central

    Wu, Cho-Kai; Lee, Jen-Kuang; Wu, Yi-Fan; Tsai, Chia-Ti; Chiang, Fu-Tien; Hwang, Juey-Jen; Lin, Jiunn-Lee; Hung, Kuan-Yu; Huang, Jenq-Wen; Lin, Jou-Wei

    2015-01-01

    Abstract Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). We examined the relationship between LVDD, major adverse cardiovascular events (MACE), and mortality in PD patients. A total of 149 patients undergoing PD with preserved left ventricular systolic function were included and followed for 3.5 years. LVDD was diagnosed (according to the European Society of Cardiology guidelines) by conventional and tissue Doppler echocardiography. Serum high-sensitivity C-reactive protein (hsCRP) was measured. The location and volume of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, and more visceral and peritoneal fat than controls. The relationship between adjusted visceral adipose tissue and LVDD became nonsignificant when hsCRP and baseline demographic data were introduced into the logistic regression model (odds ratio = 1.52, P = 0.07). Subsequent hierarchical multivariate Cox regression analysis showed that LVDD was one of the most powerful determinants of MACE and mortality after adjusting for all confounding factors (hazard ratio [HR]: 1.71, 95% confidence interval [CI]: 1.43–3.51, P = 0.02 and HR: 2.25, 95% CI: 1.45–2.91, P = 0.04, respectively). Systemic inflammation (hsCRP) was also significantly associated with MACE and mortality (HR: 2.03, P = 0.03 and HR: 2.16, P = 0.04, respectively). LVDD is associated with systemic inflammation and increased visceral fat in patients undergoing PD. LVDD is also a sensitive, independent indicator of future MACE and mortality in PD patients. PMID:25997054

  13. Safety Testing of Left Ventricular Vent Valves.

    PubMed

    Gavin, Caroline; Coblentz, John; Acsell, Jeffrey R; Shackelford, Anthony G; Sistino, Joseph J

    2015-03-01

    Vent vacuum relief valves (VRVs) are used to limit the negative pressure at the ventricular vent catheter tip as well as prevent reversal of blood flow and prevention of air embolism. The purpose of this study was to evaluate the performance of three commercially available ventricular vent valves. The negative pressure at which the vent valve opened was measured at the valve inlet using high-fidelity pressure transducers. Also, the flow rate at which air entrainment occurred due to valve opening was recorded. Using a 51.5 cm column of saline, the resistance for each valve was calculated. The mean ± SD opening negative pressures were -231.3 ± 35.2 mmHg for the Quest Medical valve, -219.8 mmHg ± 17.2 for the Sorin valve, and -329.6 · 38.0 mmHg for the Terumo valve. The red Quest Medical valve opened at a lower flow (1.44 ± .03 L/min) than the dark blue Sorin valve (2.93 ± .01 L/min) and light blue LH130 Terumo valve (2.36 ± .02 L/min). The Sorin valve had the least resistance of 34.1 dyn-s/cm, followed by the Terumo LH130 valve resistance of 58.1 dyn·s/cm5, and the Quest Medical VRV-II valve with a resistance of 66.5 dyn·s/cm. We found that the valves are significantly different in the negative pressure generated. Understanding the limitations of these devices is important to reduce the occurrence of adverse events associated with venting and to select the best device for a specific clinical application. PMID:26390676

  14. Molecular mechanisms of ventricular hypoplasia.

    PubMed

    Srivastava, D; Gottlieb, P D; Olson, E N

    2002-01-01

    We have established the beginnings of a road map to understand how ventricular cells become specified, differentiate, and expand into a functional cardiac chamber (Fig. 5). The transcriptional networks described here provide clear evidence that disruption of pathways affecting ventricular growth could be the underlying etiology in a subset of children born with malformation of the right or left ventricle. As we learn details of the precise mechanisms through which the critical factors function, the challenge will lie in devising innovative methods to augment or modify the effects of gene mutations on ventricular development. Because most congenital heart disease likely occurs in a setting of heterozygous, predisposing mutations of one or more genes, modulation of activity of critical pathways in a preventive fashion may be useful in averting disease in genetically susceptible individuals. PMID:12858532

  15. MiR-155 Knockout in Fibroblasts Improves Cardiac Remodeling by Targeting Tumor Protein p53-Inducible Nuclear Protein 1.

    PubMed

    He, Wangwei; Huang, He; Xie, Qiang; Wang, Zhiqiang; Fan, Yang; Kong, Bin; Huang, Dan; Xiao, Yali

    2016-07-01

    Cardiac remodeling caused by acute myocardial infarction (AMI) represents a major challenge for heart failure research. MiR-155 has been identified as a key mediator of cardiac inflammation and hypertrophy. In this study, we investigate the role of miR-155 in cardiac remodeling induced by AMI. We demonstrate that miR-155 expressed in cardiac fibroblasts is a potent contributor to cardiac remodeling. We reveal that in vivo, miR-155 knockout improves left ventricular function, reduces infarct size, and attenuates collagen deposition, whereas overexpression of miR-155 produces the opposite effects. MiR-155 knockout also inhibits cardiac fibroblast proliferation and differentiation into myofibroblasts. In addition, downregulation of tumor protein p53-inducible nuclear protein 1 (TP53INP1) by small interfering RNA reverses the effects of miR-155 knockout on cardiac fibroblasts. Our data reveal that knockout of miR-155 in cardiac fibroblasts improves cardiac remodeling by targeting TP53INP1, which may be a novel treatment strategy for cardiac remodeling. PMID:26589288

  16. Genetics Home Reference: catecholaminergic polymorphic ventricular tachycardia

    MedlinePlus

    ... for This Page Cerrone M, Napolitano C, Priori SG. Catecholaminergic polymorphic ventricular tachycardia: A paradigm to understand ... on PubMed Central Liu N, Ruan Y, Priori SG. Catecholaminergic polymorphic ventricular tachycardia. Prog Cardiovasc Dis. 2008 ...

  17. Mitochondria Oxidative Stress, Connexin43 Remodeling, and Sudden Arrhythmic Death

    PubMed Central

    Sovari, Ali A.; Rutledge, Cody A.; Jeong, Euy-Myoung; Dolmatova, Elena; Arasu, Divya; Liu, Hong; Vahdani, Nooshin; Gu, Lianzhi; Zandieh, Shadi; Xiao, Lei; Bonini, Marcelo G.; Duffy, Heather S.; Dudley, Samuel C.

    2013-01-01

    Background Previously, we showed a mouse model (ACE8/8) of cardiac renin-angiotensin system (RAS) activation has a high rate of spontaneous ventricular tachycardia (VT) and sudden cardiac death (SCD) secondary to a reduction in connexin43 (Cx43) level. Angiotensin-II activation increases reactive oxygen species (ROS) production, and ACE8/8 mice show increased cardiac ROS. We sought to determine the source of ROS and if ROS played a role in the arrhythmogenesis. Methods and Results Wild-type and ACE8/8 mice with and without two weeks of treatment with L-NIO (nitric oxide synthase inhibitor), sepiapterin (precursor of tetrahydrobiopterin), MitoTEMPO (mitochondria-targeted antioxidant), TEMPOL (a general antioxidant), apocynin (NADPH oxidase inhibitor), allopurinol (xanthine oxidase inhibitor), and ACE8/8 crossed with P67 dominant negative mice to inhibit the NADPH oxidase were studied. Western blotting, detection of mitochondrial ROS by MitoSOX Red, electron microscopy, immunohistochemistry, fluorescent dye diffusion technique for functional assessment of Cx43, telemetry monitoring, and in-vivo electrophysiology studies were performed. Treatment with MitoTEMPO reduced SCD in ACE8/8 mice (from 74% to 18%, P<0.005), decreased spontaneous ventricular premature beats, decreased VT inducibility (from 90% to 17%, P<0.05), diminished elevated mitochondrial ROS to the control level, prevented structural damage to mitochondria, resulted in 2.6 fold increase in Cx43 level at the gap junctions, and corrected gap junction conduction. None of the other antioxidant therapies prevented VT and SCD in ACE8/8 mice. Conclusions Mitochondrial oxidative stress plays a central role in angiotensin II-induced gap junction remodeling and arrhythmia. Mitochondria-targeted antioxidants may be effective antiarrhythmic drugs in cases of RAS activation. PMID:23559673

  18. Dealing with surgical left ventricular assist device complications

    PubMed Central

    Kilic, Arman; Acker, Michael A.

    2015-01-01

    Left ventricular assist devices (LVAD) will undoubtedly have an increasing role due to the aging population, anticipated concomitant increase in the prevalence of end-stage heart failure, and improvements in LVAD technology and outcomes. As with any surgical procedure, LVAD implantation is associated with an adverse event profile. Such complications of LVAD therapy include bleeding, infection, pump thrombosis, right heart failure, device malfunction, and stroke. Although each has a unique management, early recognition and diagnosis of these complications is uniformly paramount. In this review, we provide an overview of managing surgical complications of LVADs. PMID:26793336

  19. Arterial–Ventricular Coupling with Aging and Disease

    PubMed Central

    Chantler, Paul D.; Lakatta, Edward G.

    2012-01-01

    Age is the dominant risk factor for cardiovascular diseases. Understanding the coupling between the left ventricle (LV) and arterial system, termed arterial–ventricular coupling (EA/ELV), provides important mechanistic insights into the complex cardiovascular system and its changes with aging in the absence and presence of disease. EA/ELV can be indexed by the ratio of effective arterial elastance (EA; a measure of the net arterial load exerted on the LV) to left ventricular end-systolic elastance (ELV; a load-independent measure of left ventricular chamber performance). Age-associated alterations in arterial structure and function, including diameter, wall thickness, wall stiffness, and endothelial dysfunction, contribute to a gradual increase in resting EA with age. Remarkably there is a corresponding increase in resting ELV with age, due to alterations to LV remodeling (loss in myocyte number, increased collagen) and function. These age-adaptations at rest likely occur, at least, in response to the age-associated increase in EA and ensure that EA/ELV is closely maintained within a narrow range, allowing for optimal energetic efficiency at the expense of mechanical efficacy. This optimal coupling at rest is also maintained when aging is accompanied by the presence of hypertension, and obesity, despite further increases in EA and ELV in these conditions. In contrast, in heart failure patients with either reduced or preserved ejection fraction, EA/ELV at rest is impaired. During dynamic exercise, EA/ELV decreases, due to an acute mismatch between the arterial and ventricular systems as ELV increases disproportionate compared to EA (≈200 vs. 40%), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. However, with advancing age the reduction in EA/ELV during acute maximal exercise is blunted, due to a blunted increase ELV. This impaired EA/ELV is further amplified in the presence of disease, and may

  20. Preoperative Prediction of Aortic Insufficiency During Ventricular Assist Device Treatment.

    PubMed

    Imamura, Teruhiko; Kinugawa, Koichiro

    2016-01-01

    Survival rate in patients with stage D heart failure has improved significantly owing to the development of continuous flow left ventricular assist devices (LVAD), but aortic insufficiency (AI) still remains one of the major unsolved complications that impairs patient quality of life. There are no established treatments for AI, and preoperative prediction and prevention of AI is needed. The opening of a native aortic valve (AV) is a sufficient condition for prevention of AI, and improvement of LV ejection fraction due to LV reverse remodeling (LVRR) is essential to open a native AV. Preoperative insufficient β-blocker treatment and pulsatile flow LVAD usage are keys for LVRR, opening of an AV, and prevention of AI. The second mechanism that leads to AI is remodeling of the aortic root and degeneration of a native AV, which results from reduced pulse pressure during LVAD support. Centrifugal or pulsatile flow LVAD usage has an advantage in terms of preserving pulsatility, and may prevent AI compared with an axial pump. There is less probability of avoiding AI with sufficient β-blocker treatment, and these patients may be good candidates for concomitant surgical intervention to a native AV at the time of LVAD implantation. PMID:26742702

  1. Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure

    PubMed Central

    Piao, Lin; Marsboom, Glenn

    2011-01-01

    Right ventricular failure (RVF) is the leading cause of death in pulmonary arterial hypertension (PAH). Some patients with pulmonary hypertension are adaptive remodelers and develop RV hypertrophy (RVH) but retain RV function; others are maladaptive remodelers and rapidly develop RVF. The cause of RVF is unclear and understudied and most PAH therapies focus on regressing pulmonary vascular disease. Studies in animal models and human RVH suggest that there is reduced glucose oxidation and increased glycolysis in both adaptive and maladaptive RVH. The metabolic shift from oxidative mitochondrial metabolism to the less energy efficient glycolytic metabolism may reflect myocardial ischemia. We hypothesize that in maladaptive RVH a vicious cycle of RV ischemia and transcription factor activation causes a shift from oxidative to glycolytic metabolism thereby ultimately promoting RVF. Interrupting this cycle, by reducing ischemia or enhancing glucose oxidation, might be therapeutic. Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, has beneficial effects on RV function and metabolism in experimental RVH, notably improving glucose oxidation and enhancing RV function. This suggests the mitochondrial dysfunction in RVH may be amenable to therapy. In this mini review, we describe the role of impaired mitochondrial metabolism in RVH, using rats with adaptive (pulmonary artery banding) or maladaptive (monocrotaline-induced pulmonary hypertension) RVH as models of human disease. We will discuss the possible mechanisms, relevant transcriptional factors, and the potential of mitochondrial metabolic therapeutics in RVH and RVF. PMID:20820751

  2. EVALUATION OF RIGHT AND LEFT VENTRICULAR DIASTOLIC FILLING

    PubMed Central

    Pasipoularides, Ares

    2013-01-01

    A conceptual fluid-dynamics framework for diastolic filling is developed. The convective deceleration load (CDL) is identified as an important determinant of ventricular inflow during the E-wave (A-wave) upstroke. Convective deceleration occurs as blood moves from the inflow anulus through larger-area cross-sections toward the expanding walls. Chamber dilatation underlies previously unrecognized alterations in intraventricular flow dynamics. The larger the chamber, the larger become the endocardial surface and the CDL. CDL magnitude affects strongly the attainable E-wave (A-wave) peak. This underlies the concept of diastolic ventriculoannular disproportion. Large vortices, whose strength decreases with chamber dilatation, ensue after the E-wave peak and impound inflow kinetic energy, averting an inflow-impeding, convective Bernoulli pressure-rise. This reduces the CDL by a variable extent depending on vortical intensity. Accordingly, the filling vortex facilitates filling to varying degrees, depending on chamber volume. The new framework provides stimulus for functional genomics research, aimed at new insights into ventricular remodeling. PMID:23585308

  3. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model

    PubMed Central

    Wang, Jessica Jen-Chu; Rau, Christoph; Avetisyan, Rozeta; Ren, Shuxun; Romay, Milagros C.; Gong, Ke Wei; Wang, Yibin; Lusis, Aldons J.

    2016-01-01

    We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls. PMID:27385019

  4. Cell-based therapy for prevention and reversal of myocardial remodeling

    PubMed Central

    Karantalis, Vasileios; Balkan, Wayne; Schulman, Ivonne H.; Hatzistergos, Konstantinos E.

    2012-01-01

    Although pharmacological and interventional advances have reduced the morbidity and mortality of ischemic heart disease, there is an ongoing need for novel therapeutic strategies that prevent or reverse progressive ventricular remodeling following myocardial infarction, the process that forms the substrate for ventricular failure. The development of cell-based therapy as a strategy to repair or regenerate injured tissue offers extraordinary promise for a powerful anti-remodeling therapy. In this regard, the field of cell therapy has made major advancements in the past decade. Accumulating data from preclinical studies have provided novel insights into stem cell engraftment, differentiation, and interactions with host cellular elements, as well as the effectiveness of various methods of cell delivery and accuracy of diverse imaging modalities to assess therapeutic efficacy. These findings have in turn guided rationally designed translational clinical investigations. Collectively, there is a growing understanding of the parameters that underlie successful cell-based approaches for improving heart structure and function in ischemic and other cardiomyopathies. PMID:22636682

  5. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

    PubMed

    Wang, Jessica Jen-Chu; Rau, Christoph; Avetisyan, Rozeta; Ren, Shuxun; Romay, Milagros C; Stolin, Gabriel; Gong, Ke Wei; Wang, Yibin; Lusis, Aldons J

    2016-07-01

    We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls. PMID:27385019

  6. [Adverse reaction of pseudoephedrine].

    PubMed

    López Lois, G; Gómez Carrasco, J A; García de Frías, E

    2005-04-01

    We present a case of a 7 years old girl who developed an episode of myoclonic movements and tremors after being medicated with a not well quantified amount of a pseudoephedrine/antihistamine combination. We want to highlight the potential toxicity of pseudoephedrine, usually administered as part of cold-syrup preparations which are used for symptomatic treatment of upper respiratory tract cough and congestion associated with the common cold and allergic rhinitis. Although these products are generally considered to be safe either by physicians and parents, we can't underestimate the potential adverse events and toxic effects that can occur when administering these medications. PMID:15826569

  7. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

    Adverse events (AEs) in medical patients are common, costly, and often preventable. Development of quality improvement programs to decrease the number and impact of AEs demands effective methods for screening for AEs on a routine basis. Here we describe the impact, types, and potential causes of AEs and review various techniques for identifying AEs. We evaluate the use of generic screening criteria in detail and describe a recent study of the sensitivity and specificity of individual generic screening criteria and combinations of these criteria. In general, the most sensitive screens were the least specific and no small sub-set of screens identified a large percentage of adverse events. Combinations of screens that were limited to administrative data were the least expensive, but none were particularly sensitive, although in practice they might be effective since routine screening is currently rarely done. As computer systems increase in sophistication sensitivity will improve. We also discuss recent studies that suggest that programs that screen for and identify AEs can be useful in reducing AE rates. While tools for identifying AEs have strengths and weaknesses, they can play an important role in organizations' quality improvement portfolios. PMID:10468381

  8. Changes in Serum Natriuretic Peptide Levels after Percutaneous Closure of Small to Moderate Ventricular Septal Defects

    PubMed Central

    Kaya, Yuksel; Akdemir, Ramazan; Gunduz, Huseyin; Murat, Sani; Bulut, Orhan; Kocayigit, İbrahim; Vatan, M. Bulent; Cakar, M. Akif; Yeter, Ekrem; Kilic, Harun; Agac, Mustafa Tarik; Acar, Zeydin

    2012-01-01

    Background. B-type natriuretic peptide has been shown to be a very sensitive and specific marker of heart failure. In this study, we aimed to investigate the effect of percutaneous closure of ventricular septal defects with Amplatzer septal occluders on brain natriuretic peptide levels. Methods. Between 2008 and 2011, 23 patients underwent successfully percutaneous ventricular septal defect closure in 4 cardiology centers. Brain natriuretic peptide levels were measured in nine patients (4 male, mean ages were 25.3 ± 14.3) who underwent percutaneous closure with Amplatzer occluders for membranous or muscular ventricular septal defects were enrolled in the study. Brain natriuretic peptide levels were measured one day before and one month after the closure. Patients were evaluated clinically and by echocardiography one month after the procedure. Results. Percutaneous closures of ventricular septal defects were successfully performed in all patients. There was not any significant adverse event in patients group during followup. Decrease in brain natriuretic peptide levels after closure were statistically significant (97.3 ± 78.6 versus 26.8 ± 15.6, P = 0.013). Conclusion. Brain Natriuretic Peptide levels are elevated in patients with ventricular septal defects as compared to controls. Percutaneous closure of Ventricular Septal Defect with Amplatzer occluders decreases the BNP levels. PMID:22629130

  9. Gender Differences in Non-Ischemic Myocardial Remodeling: Are They Due to Estrogen Modulation of Cardiac Mast Cells and/or Membrane Type 1 Matrix Metalloproteinase

    PubMed Central

    Janicki, Joseph S.; Spinale, Francis G.; Levick, Scott P.

    2013-01-01

    SUMMARY This review is focused on gender differences in cardiac remodeling secondary to sustained increases in cardiac volume (VO) and generated pressure (PO). Estrogen has been shown to favorably alter the course of VO-induced remodeling. That is, the VO-induced increased extracellular matrix proteolytic activity and mast cell degranulation responsible for the adverse cardiac remodeling in males and ovariectomized rodents do not occur in intact premenopausal females. While less is known regarding the mechanisms responsible for female cardioprotection in PO-induced stress, gender differences in remodeling have been reported indicating the ability of premenopausal females to adequately compensate. In view of the fact that, in male mice with PO, mast cells have been shown to play a role in the adverse remodeling suggests favorable estrogen modification of mast cell phenotype may also be responsible for cardioprotection in females with PO. Thus, while evidence is accumulating regarding premenopausal females being cardioprotected; there remains the need for in-depth studies to identify critical downstream molecular targets that are under the regulation of estrogen and relevant to cardiac remodeling. Such studies would result in the development of therapy which provides cardioprotection while avoiding the adverse effects of systemic estrogen delivery. PMID:23417570

  10. [Drug-induced ventricular tachycardia].

    PubMed

    Fauchier, J P; Fauchier, L; Babuty, D; Breuillac, J C; Cosnay, P; Rouesnel, P

    1993-05-01

    Certain drugs can induce ventricular tachycardia (VT) by creating reentry, ventricular after potentials or exaggerating the slope of phase 4. These may or may not be symptomatic, sustained or non-sustained and have variable ECG appearances: monomorphic or polymorphic, bidirectional, torsades de pointes. They risk degenerating into ventricular flutter of fibrillation and have been held responsible for the increased mortality observed unexpectedly in some long-term treatments. The drugs responsible are mainly those used in cardiology, probably due to predisposing circumstances (cardiomegaly, cardiac failure, previous severe ventricular arrhythmias, therapeutic associations, metabolic abnormalities). These include primarily the antiarrhythmic drugs (IA, IC, sotalol and bepridil), digitalis, sympathomimetics and phosphodiesterase inhibitors. These complications may be toxic or idiosyncratic, in patients with or without cardiac disease, and may also occur with other drugs: vasodilators and anti-anginal drugs (lidoflazine, vincamine, fenoxedil), psychotropic agents (phenothiazine and imipramine), antimitotics, antimalarials (chloroquine) or antibiotics (erythromycin, pentamidine). The prognosis is severe and the treatment is often difficult which makes prevention, helped by repeated surface ECG (or Holter monitoring), very important with careful assessment of patients at risk. PMID:8267504

  11. Progress versus precision: challenges in clinical trial design for left ventricular assist devices.

    PubMed

    Parides, Michael K; Moskowitz, Alan J; Ascheim, Deborah D; Rose, Eric A; Gelijns, Annetine C

    2006-09-01

    New left ventricular assist devices promise fewer adverse events but, currently, only minor improvements in survival. Small (survival) treatment effects, limited patient populations, and the increasing number of left ventricular assist devices in development challenge the efficient conduct of premarketing trials (especially in destination therapy) and, maybe more importantly, hamper innovation. Novel trial designs would facilitate this process. Among a range of trial designs, we opt for small randomized trials, which would preserve the advantages of randomization and also allow for a shorter enrollment period. We also advocate an evidence shift toward postmarketing studies, with the Interagency Registry of Mechanically Assisted Circulatory Support providing a robust infrastructure. PMID:16928569

  12. Lead Poisoning in Remodeling of Old Homes

    ERIC Educational Resources Information Center

    Barnes, Bart

    1973-01-01

    An article based on Dr. Muriel D. Wolf's study of elevated blood lead levels in children and adults present during the remodeling of old homes. Lead poisoning examples, symptoms, and precautions are given. (ST)

  13. Bone Remodeling Under Pathological Conditions.

    PubMed

    Xiao, Wenmei; Li, Shuai; Pacios, Sandra; Wang, Yu; Graves, Dana T

    2016-01-01

    Bone is masterfully programmed to repair itself through the coupling of bone formation following bone resorption, a process referred to as coupling. In inflammatory or other conditions, the balance between bone resorption and bone formation shifts so that a net bone loss results. This review focuses on four pathologic conditions in which remodeling leads to net loss of bone, postmenopausal osteoporosis, arthritis, periodontal disease, and disuse bone loss, which is similar to bone loss associated with microgravity. In most of these there is an acceleration of the resorptive process due to increased formation of bone metabolic units. This initially leads to a net bone loss since the time period of resorption is much faster than the time needed for bone formation that follows. In addition, each of these processes is characterized by an uncoupling that leads to net bone loss. Mechanisms responsible for increased rates of bone resorption, i.e. the formation of more bone metabolic units, involve enhanced expression of inflammatory cytokines and increased expression of RANKL. Moreover, the reasons for uncoupling are discussed which range from a decrease in expression of growth factors and bone morphogenetic proteins to increased expression of factors that inhibit Wnt signaling. PMID:26599114

  14. Differences in Left Versus Right Ventricular Electrophysiological Properties in Cardiac Dysfunction and Arrhythmogenesis

    PubMed Central

    Molina, Cristina E; Heijman, Jordi; Dobrev, Dobromir

    2016-01-01

    A wide range of ion channels, transporters, signaling pathways and tissue structure at a microscopic and macroscopic scale regulate the electrophysiological activity of the heart. Each region of the heart has optimised these properties based on its specific role during the cardiac cycle, leading to well-established differences in electrophysiology, Ca2+ handling and tissue structure between atria and ventricles and between different layers of the ventricular wall. Similarly, the right ventricle (RV) and left ventricle (LV) have different embryological, structural, metabolic and electrophysiological features, but whether interventricular differences promote differential remodeling leading to arrhythmias is not well understood. In this article, we will summarise the available data on intrinsic differences between LV and RV electrophysiology and indicate how these differences affect cardiac function. Furthermore, we will discuss the differential remodeling of both chambers in pathological conditions and its potential impact on arrhythmogenesis. PMID:27403288

  15. KLF5 mediates vascular remodeling via HIF-1α in hypoxic pulmonary hypertension.

    PubMed

    Li, Xiaochen; He, Yuanzhou; Xu, Yongjian; Huang, Xiaomin; Liu, Jin; Xie, Min; Liu, Xiansheng

    2016-02-15

    Hypoxic pulmonary hypertension (HPH) is characterized by active vasoconstriction and profound vascular remodeling. KLF5, a zinc-finger transcription factor, is involved in the excessive proliferation and apoptotic resistance phenotype associated with monocrotaline-induced pulmonary hypertension. However, the molecular mechanisms of KLF5-mediated pathogenesis of HPH are largely undefined. Adult male Sprague-Dawley rats were exposed to normoxia or hypoxia (10% O2) for 4 wk. Hypoxic rats developed pulmonary arterial remodeling and right ventricular hypertrophy with significantly increased right ventricular systolic pressure. The levels of KLF5 and hypoxia-inducible factor-1α (HIF-1α) were upregulated in distal pulmonary arterial smooth muscle from hypoxic rats. The knockdown of KLF5 via short-hairpin RNA attenuated chronic hypoxia-induced hemodynamic and histological changes in rats. The silencing of either KLF5 or HIF-1α prevented hypoxia-induced (5%) proliferation and migration and promoted apoptosis in human pulmonary artery smooth muscle cells. KLF5 was immunoprecipitated with HIF-1α under hypoxia and acted as an upstream regulator of HIF-1α. The cell cycle regulators cyclin B1 and cyclin D1 and apoptosis-related proteins including bax, bcl-2, survivin, caspase-3, and caspase-9, were involved in the regulation of KLF5/HIF-1α-mediated cell survival. This study demonstrated that KLF5 plays a crucial role in hypoxia-induced vascular remodeling in an HIF-1α-dependent manner and provided a better understanding of the pathogenesis of HPH. PMID:26702149

  16. Incomplete RV Remodeling After Transcatheter ASD Closure in Pediatric Age.

    PubMed

    Agha, Hala M; El-Saiedi, Sonia A; Shaltout, Mohamed F; Hamza, Hala S; Nassar, Hayat H; Abdel-Aziz, Doaa M; Tantawy, Amira Esmat El

    2015-10-01

    Published data showing the intermediate effect of transcatheter device closure of atrial septal defect (ASD) in the pediatric age-group are scarce. The objective of the study was to assess the effects of transcatheter ASD closure on right and left ventricular functions by tissue Doppler imaging (TDI). The study included 37 consecutive patients diagnosed as ASD secundum by transthoracic echocardiography and TEE and referred for transcatheter closure at Cairo University Specialized Pediatric Hospital, Egypt, from October 2010 to July 2013. Thirty-seven age- and sex-matched controls were selected. TDI was obtained using the pulsed Doppler mode, interrogating the right cardiac border (the tricuspid annulus) and lateral mitral annulus, and myocardial performance index (MPI) was calculated at 1-, 3-, 6- and 12-month post-device closure. Transcatheter closure of ASD and echocardiographic examinations were successfully performed in all patients. There were no significant differences between two groups as regards the age, gender, weight or BSA. TDI showed that patients with ASD had significantly prolonged isovolumetric contraction, relaxation time and MPI compared with control group. Decreased tissue Doppler velocities of RV and LV began at one-month post-closure compared with the controls. Improvement in RVMPI and LVMPI began at 1-month post-closure, but they are still prolonged till 1 year. Reverse remodeling of right and left ventricles began 1 month after transcatheter ASD closure, but did not completely normalize even after 1 year of follow-up by tissue Doppler imaging. PMID:25981566

  17. Revascularization in Severe Left Ventricular Dysfunction: Does Myocardial Viability Even Matter?

    PubMed Central

    Singh, Pahul; Sethi, Nishant; Kaur, Navneet; Kozman, Hani

    2015-01-01

    Left ventricular dysfunction is a powerful prognostic predictor in patients with coronary artery disease and increasing number of patients with CAD and ischemic left ventricular (LV) dysfunction is a major clinical problem. Congestive heart failure is a frequent complication which is associated with significant health care costs and two–third of cases have ischemic cardiomyopathy. In such patients, coronary revascularization can lead to symptomatic and prognostic improvement and reversal of LV remodeling which led to the concept of viable myocardium to select patients in whom recovery of LV function and improvement of prognosis will outweigh the risk of surgical revascularization. The aim of this review article is to understand the different modalities for assessing myocardial viability and clinical impact of revascularization in relation to the evidence of viability in patients with LV dysfunction. PMID:26157339

  18. Exercise Training Reduces Cardiac Dysfunction and Remodeling in Ovariectomized Rats Submitted to Myocardial Infarction

    PubMed Central

    de Almeida, Simone Alves; Claudio, Erick Roberto Gonçalves; Mengal, Vinícius Franskoviaky; de Oliveira, Suelen Guedes; Merlo, Eduardo; Podratz, Priscila Lang; Gouvêa, Sônia Alves; Graceli, Jones Bernardes; de Abreu, Gláucia Rodrigues

    2014-01-01

    The aim of this study was to evaluate whether exercise training (ET) prevents or minimizes cardiac dysfunction and pathological ventricular remodeling in ovariectomized rats subjected to myocardial infarction (MI) and to examine the possible mechanisms involved in this process. Ovariectomized Wistar rats were subjected to either MI or fictitious surgery (Sham) and randomly divided into the following groups: Control, OVX+SHAMSED, OVX+SHAMET, OVX+MISED and OVX+MIET. ET was performed on a motorized treadmill (5x/wk, 60 min/day, 8 weeks). Cardiac function was assessed by ventricular catheterization and Dihydroethidium fluorescence (DHE) was evaluated to analyze cardiac oxidative stress. Histological analyses were made to assess collagen deposition, myocyte hypertrophy and infarct size. Western Blotting was performed to analyze the protein expression of catalase and SOD-2, as well as Gp91phox and AT1 receptor (AT1R). MI-trained rats had significantly increased in +dP/dt and decreased left ventricular end-diastolic pressure compared with MI-sedentary rats. Moreover, oxidative stress and collagen deposition was reduced, as was myocyte hypertrophy. These effects occurred in parallel with a reduction in both AT1R and Gp91phox expression and an increase in catalase expression. SOD-2 expression was not altered. These results indicate that ET improves the functional cardiac parameters associated with attenuation of cardiac remodeling in ovariectomized rats subjected to MI. The mechanism seems to be related to a reduction in the expression of both the AT1 receptor and Gp91phox as well as an increase in the antioxidant enzyme catalase, which contributes to a reduction in oxidative stress. Therefore, ET may be an important therapeutic target for the prevention of heart failure in postmenopausal women affected by MI. PMID:25551214

  19. Remodeling kitchens: A smorgasbord of energy savings

    SciTech Connect

    Sullivan, B.

    1995-09-01

    The kitchen is often the busiest room in the house and is most likely to remodeled repeatedly over the life of a house. The kitchen also represents a concentration of household energy use. Remodeling a kitchen can mean introducing a host of new energy-saving features or making major energy blunders. This article discusses ways to utilized the best features: layout and design; appliances; lighting; windows and skylights; ventilation; insulation and air sealing; water; household recycling; green building materials.

  20. Effect of material damping on bone remodelling.

    PubMed

    Misra, J C; Samanta, S

    1987-01-01

    This paper considers the effect of internal material damping on the stresses, strains, and surface and internal remodelling behaviour in a section of axisymmetrical bone with a force-fitted axially oriented medullary pin. The bone response to several loading situations is modelled using visco-elastic equations. An approximate method is developed to analyse the proposed mathematical model. By considering a numerical example, the effect of material damping on the remodelling stresses is quantified. PMID:3584150

  1. Chromatin remodeling by nucleosome disassembly in vitro.

    PubMed

    Lorch, Yahli; Maier-Davis, Barbara; Kornberg, Roger D

    2006-02-28

    The RSC chromatin-remodeling complex completely disassembles a nucleosome in the presence of the histone chaperone Nap1 and ATP. Disassembly occurs in a stepwise manner, with the removal of H2A/H2B dimers, followed by the rest of the histones and the release of naked DNA. RSC and related chromatin-remodeling complexes may be responsible for the removal of promoter nucleosomes during transcriptional activation in vivo. PMID:16492771

  2. Biomechanics of vascular mechanosensation and remodeling

    PubMed Central

    Baeyens, Nicolas; Schwartz, Martin A.

    2016-01-01

    Flowing blood exerts a frictional force, fluid shear stress (FSS), on the endothelial cells that line the blood and lymphatic vessels. The magnitude, pulsatility, and directional characteristics of FSS are constantly sensed by the endothelium. Sustained increases or decreases in FSS induce vessel remodeling to maintain proper perfusion of tissue. In this review, we discuss these mechanisms and their relevance to physiology and disease, and propose a model for how information from different mechanosensors might be integrated to govern remodeling. PMID:26715421

  3. In vivo collagen turnover during development of thyroxine-induced left ventricular hypertrophy.

    PubMed

    Karim, M A; Ferguson, A G; Wakim, B T; Samarel, A M

    1991-02-01

    Cardiac fibroblasts synthesize large amounts of procollagens, yet only a small fraction of mature collagens accumulate in the extracellular matrix. To determine the roles of intracellular degradation of newly synthesized procollagens and extracellular degradation of mature collagens during normal growth and during thyroxine-induced left ventricular hypertrophy, in vivo left ventricular procollagen synthetic rates were assessed in control rats and rats treated with L-thyroxine for 1, 2, 4, and 8 wk (1 mg.kg-1.day-1). A modification of the flooding infusion method was developed using measurements of cardiac prolyl-tRNA, and tissue-free and protein-bound hydroxyproline specific radioactivities 60 min after intravenous administration of a massive dose of [3H]proline. Degradative rates of newly synthesized procollagens and mature collagens were then derived as the difference between rates of procollagen synthesis and collagen accumulation. Left ventricular procollagen synthetic rates were markedly increased after 1 wk of hormone administration (256 +/- 16 and 166 +/- 13 micrograms/day per left ventricle for thyroxine-treated and control animals, respectively; P less than 0.01). An even greater increase in procollagen synthetic rates was observed after 8 wk (438 +/- 46 and 202 +/- 18 micrograms/day for thyroxine-treated and control animals, respectively; P less than 0.01). Despite increased procollagen synthesis, disproportionate accumulation of fibrillar collagens (assessed as the relative concentration of protein-bound hydroxyproline in left ventricular tissue) did not occur. Derived left ventricular degradative rates for newly synthesized procollagens as well as for mature collagens were increased in thyroxine-treated animals. Increased procollagen synthesis, enhanced flux of newly synthesized procollagens through intracellular degradative pathways, and extensive extracellular matrix remodeling without disproportionate collagen accumulation are characteristics of this

  4. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

  5. Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias

    PubMed Central

    Dhein, Stefan; Seidel, Thomas; Salameh, Aida; Jozwiak, Joanna; Hagen, Anja; Kostelka, Martin; Hindricks, Gerd; Mohr, Friedrich-Wilhelm

    2014-01-01

    Coordinated electrical activation of the heart is essential for the maintenance of a regular cardiac rhythm and effective contractions. Action potentials spread from one cell to the next via gap junction channels. Because of the elongated shape of cardiomyocytes, longitudinal resistivity is lower than transverse resistivity causing electrical anisotropy. Moreover, non-uniformity is created by clustering of gap junction channels at cell poles and by non-excitable structures such as collagenous strands, vessels or fibroblasts. Structural changes in cardiac disease often affect passive electrical properties by increasing non-uniformity and altering anisotropy. This disturbs normal electrical impulse propagation and is, consequently, a substrate for arrhythmia. However, to investigate how these structural changes lead to arrhythmias remains a challenge. One important mechanism, which may both cause and prevent arrhythmia, is the mismatch between current sources and sinks. Propagation of the electrical impulse requires a sufficient source of depolarizing current. In the case of a mismatch, the activated tissue (source) is not able to deliver enough depolarizing current to trigger an action potential in the non-activated tissue (sink). This eventually leads to conduction block. It has been suggested that in this situation a balanced geometrical distribution of gap junctions and reduced gap junction conductance may allow successful propagation. In contrast, source-sink mismatch can prevent spontaneous arrhythmogenic activity in a small number of cells from spreading over the ventricle, especially if gap junction conductance is enhanced. Beside gap junctions, cell geometry and non-cellular structures strongly modulate arrhythmogenic mechanisms. The present review elucidates these and other implications of passive electrical properties for cardiac rhythm and arrhythmogenesis. PMID:25404918

  6. Simulated Microgravity and Recovery-Induced Remodeling of the Left and Right Ventricle

    PubMed Central

    Zhong, Guohui; Li, Yuheng; Li, Hongxing; Sun, Weijia; Cao, Dengchao; Li, Jianwei; Zhao, Dingsheng; Song, Jinping; Jin, Xiaoyan; Song, Hailin; Yuan, Xinxin; Wu, Xiaorui; Li, Qi; Xu, Qing; Kan, Guanghan; Cao, Hongqing; Ling, Shukuan; Li, Yingxian

    2016-01-01

    Physiological adaptations to microgravity involve alterations in cardiovascular systems. These adaptations result in cardiac remodeling and orthostatic hypotension. However, the response of the left ventricle (LV) and right ventricle (RV) following hindlimb unloading (HU) and hindlimb reloading (HR) is not clear and the underlying mechanism remains to be understood. In this study, three groups of mice were subjected to HU by tail suspension for 28 days. Following this, two groups were allowed to recover for 7 or 14 days. The control group was treated equally, with the exception of tail suspension. Echocardiography was performed to detect the structure and function changes of heart. Compared with the control, the HU group of mice showed reduced LV-EF (ejection fraction), and LV-FS (fractional shortening). However, mice that were allowed to recover for 7 days after HU (HR-7d) showed increased LVIDs (systolic LV internal diameter) and LV Vols (systolic LV volume). Mice that recovered for 14 days (HR-14d) returned to the normal state. In comparison, RV-EF and RV-FS didn't recover to the normal conditions till being reloaded for 14 days. Compared with the control, RVIDd (diastolic RV internal diameter), and RV Vold (diastolic RV volume) were reduced in HU group and recovered to the normal conditions in HR-7d and HR-14d groups, in which groups RVIDs (systolic RV internal diameter) and RV Vols (systolic RV volume) were increased. Histological analysis and cardiac remodeling gene expression results indicated that HU induces left and right ventricular remodeling. Western blot demonstrated that the phosphorylation of HDAC4 and ERK1/2 and the ratio of LC3-II / LC3-I, were increased following HU and recovered following HR in both LV and RV, and the phosphorylation of AMPK was inhibited in both LV and RV following HU, but only restored in LV following HR for 14 days. These results indicate that simulated microgravity leads to cardiac remodeling, and the remodeling changes can

  7. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

  8. Outpatient Outcomes of Pediatric Patients with Left Ventricular Assist Devices.

    PubMed

    Chen, Sharon; Lin, Aileen; Liu, Esther; Gowan, Maryalice; May, Lindsay J; Doan, Lan N; Almond, Christopher S; Maeda, Katsuhide; Reinhartz, Olaf; Hollander, Seth A; Rosenthal, David N

    2016-01-01

    Outpatient experience of children supported with continuous-flow ventricular assist devices (CF-VAD) is limited. We reviewed our experience with children discharged with CF-VAD support. All pediatric patients <18 years old with CF-VADs implanted at our institution were included. Discharge criteria included a stable medication regimen, completion of a VAD education program and standardized rehabilitation plan, and presence of a caregiver. Hospital readmissions (excluding scheduled admissions) were reviewed. Adverse events were defined by Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria. Of 17 patients with CF-VADs, 8 (47%) were discharged from the hospital (1 HeartWare ventricular assist device (Heartware Inc., Framingham, MA), 7 HeartMate II (Thoratec Corp, Pleasanton, CA)). Median age was 15.3 (range 9.6-17.1) years and weight was 50.6 (33.6-141) kg. Device strategies were destination therapy (DT; n = 4) and bridge to transplant (n = 4). Patients spent a median 49 (26-107) days hospitalized postimplant and had 2 (1-5) hospital readmissions. Total support duration was 3,154 patient-days, with 2,413 as outpatient. Most frequent adverse events were device malfunction and arrhythmias. There was one death because of pump thrombosis and no bleeding or stroke events. Overall adverse event rate was 15.22 per 100 patient-months. Early experience suggests that children with CF-VADs can be safely discharged. Device malfunction and arrhythmia were the most common adverse events but were recognized quickly with structured outpatient surveillance. PMID:26720740

  9. Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing

    NASA Technical Reports Server (NTRS)

    Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.

    1996-01-01

    OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular

  10. Hydrogen sulfide improves cardiomyocytes electrical remodeling post ischemia/reperfusion injury in rats.

    PubMed

    Sun, Ying-Gang; Wang, Xin-Yan; Chen, Xiu; Shen, Cheng-Xing; Li, Yi-Gang

    2015-01-01

    Hydrogen sulfide (H2S), produced by cystanthionine-γ-lysase (CSE) in the cardiovascular system, is an endogenous gaseous mediator exerting pronounced physiological effects as the third gasotransmitter in addition to nitric oxide (NO) and carbon monoxide (CO). Accumulating evidence indicated that H2S could mediate the cardioprotective effects in myocardial ischemia model. Ventricular arrhythmia is the most important risk factor for cardiac mortality and sudden death after acute myocardial infarction (AMI). The potential impact of H2S on cardiomyocytes electrical remodeling post ischemic insult is not fully explored now. Present study investigated the role of H2S on cardiomyocytes electrical remodeling in rats with ischemia/reperfusion injury. H2S concentration was reduced and arrhythmia score was increased in this model. CSE mRNA level was also upregulated in the ischemic myocardium. Exposure to exogenous NaHS reduced the action potential duration (APD), inhibited L-type Ca(2+) channels and activated K(ATP) channels in cardiomyocytes isolated from ischemic myocardium Exogenous H2S application improves electrical remodeling in cardiomyocytes isolated from ischemic myocardium. These results indicated that reduced H2S level might be linked to ischemia/reperfusion induced arrhythmias. PMID:25755736

  11. Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

    PubMed Central

    Li, Shaojun; Han, Dong; Zhang, Yonghong; Xie, Xinming; Ke, Rui; Zhu, Yanting; Liu, Lu; Song, Yang; Yang, Lan; Li, Manxiang

    2016-01-01

    Background The current study was performed to investigate the effect of adenosine monophosphate (AMP) – activated protein kinase (AMPK) activation on the extracellular matrix (ECM) remodeling of pulmonary arteries in pulmonary arterial hypertension (PAH) and to address its potential mechanisms. Material/Methods PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) into Sprague-Dawley rats. Metformin (MET) was administered to activate AMPK. Immunoblotting was used to determine the phosphorylation and expression of AMPK and expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Gelatin zymography was performed to determine the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9. Results Activation of AMPK by MET significantly reduced the right ventricle systolic pressure and the right ventricular hypertrophy in MCT-induced rat PAH model, and partially inhibited the ECM remodeling of pulmonary arteries. These effects were coupled with the decrease of MMP-2/9 activity and TIMP-1 expression. Conclusions This study suggests that activation of AMPK benefits PAH by inhibiting ECM remodeling of pulmonary arteries. Enhancing AMPK activity might have potential value in clinical treatment of PAH. PMID:26978596

  12. Dynamics of the Ethanolamine Glycerophospholipid Remodeling Network

    PubMed Central

    Hermansson, Martin; Somerharju, Pentti; Chuang, Jeffrey

    2012-01-01

    Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE) remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1) sn1 and sn2 acyl positions are independently remodeled; (2) remodeling reaction rates are constant over time; and (3) acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In constrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data. PMID:23251394

  13. Mitochondria, myocardial remodeling, and cardiovascular disease.

    PubMed

    Verdejo, Hugo E; del Campo, Andrea; Troncoso, Rodrigo; Gutierrez, Tomás; Toro, Barbra; Quiroga, Clara; Pedrozo, Zully; Munoz, Juan Pablo; Garcia, Lorena; Castro, Pablo F; Lavandero, Sergio

    2012-12-01

    The process of muscle remodeling lies at the core of most cardiovascular diseases. Cardiac adaptation to pressure or volume overload is associated with a complex molecular change in cardiomyocytes which leads to anatomic remodeling of the heart muscle. Although adaptive at its beginnings, the sustained cardiac hypertrophic remodeling almost unavoidably ends in progressive muscle dysfunction, heart failure and ultimately death. One of the features of cardiac remodeling is a progressive impairment in mitochondrial function. The heart has the highest oxygen uptake in the human body and accordingly it has a large number of mitochondria, which form a complex network under constant remodeling in order to sustain the high metabolic rate of cardiac cells and serve as Ca(2+) buffers acting together with the endoplasmic reticulum (ER). However, this high dependence on mitochondrial metabolism has its costs: when oxygen supply is threatened, high leak of electrons from the electron transport chain leads to oxidative stress and mitochondrial failure. These three aspects of mitochondrial function (Reactive oxygen species signaling, Ca(2+) handling and mitochondrial dynamics) are critical for normal muscle homeostasis. In this article, we will review the latest evidence linking mitochondrial morphology and function with the process of myocardial remodeling and cardiovascular disease. PMID:22972531

  14. Epigenomic regulation of oncogenesis by chromatin remodeling.

    PubMed

    Kumar, R; Li, D-Q; Müller, S; Knapp, S

    2016-08-25

    Disruption of the intricate gene expression program represents one of major driving factors for the development, progression and maintenance of human cancer, and is often associated with acquired therapeutic resistance. At the molecular level, cancerous phenotypes are the outcome of cellular functions of critical genes, regulatory interactions of histones and chromatin remodeling complexes in response to dynamic and persistent upstream signals. A large body of genetic and biochemical evidence suggests that the chromatin remodelers integrate the extracellular and cytoplasmic signals to control gene activity. Consequently, widespread dysregulation of chromatin remodelers and the resulting inappropriate expression of regulatory genes, together, lead to oncogenesis. We summarize the recent developments and current state of the dysregulation of the chromatin remodeling components as the driving mechanism underlying the growth and progression of human tumors. Because chromatin remodelers, modifying enzymes and protein-protein interactions participate in interpreting the epigenetic code, selective chromatin remodelers and bromodomains have emerged as new frontiers for pharmacological intervention to develop future anti-cancer strategies to be used either as single-agent or in combination therapies with chemotherapeutics or radiotherapy. PMID:26804164

  15. An autopsy case of cardiac tamponade caused by a ruptured ventricular aneurysm associated with acute myocarditis.

    PubMed

    Kondo, Takeshi; Nagasaki, Yasushi; Takahashi, Motonori; Nakagawa, Kanako; Kuse, Azumi; Morichika, Mai; Sakurada, Makoto; Asano, Migiwa; Ueno, Yasuhiro

    2016-01-01

    We report an autopsy case of hemopericardium caused by rupture of a ventricular aneurysm associated with acute myocarditis in an infant boy aged 2 years and 10 months. Three days before his death, the patient developed fever. On the day of death, he described an urge to defecate and attempted to do so in an upright position. While straining to defecate without success for a prolonged period, he stopped breathing and collapsed. On autopsy, his heart weighed 91.7 g and cardiac tamponade was evident, the pericardial cavity being filled with 140 mL of blood that had come from a 1.5-cm-long rupture in a 2.7×1.5 cm ventricular aneurysm in the posterior left ventricular wall. Patchy grayish-white discoloration was noted in the myocardium. Histologically, CD3-positive T lymphocytic infiltration accompanied by pronounced macrophage infiltration was observed in the myocardium. Hemorrhagic necrosis was detected in the area of the ventricular aneurysm. Staining for matrix metalloproteinase (MMP) expression revealed abundant MMP-2, MMP-7, and MMP-9. Polymerase chain reaction to detect viruses failed to identify any specific causative viruses in the myocardium. In this case of lymphocytic (viral) and histiocytic myocarditis with pronounced macrophage infiltration and upregulation of MMP expression, myocardial remodeling and associated wall weakening had resulted in formation and rupture of an aneurysm. PMID:26832375

  16. Impact of prehypertension on left ventricular mass and QT dispersion in adult black Nigerians

    PubMed Central

    Ale, OK; Ajuluchukwu, JN; Oke, DA; Mbakwem, AC

    2014-01-01

    Summary Background Prehypertension has been associated with target-organ damage. This study sought to determine the impact of prehypertension (PHT) on QT dispersion and left ventricular hypertrophy (LVH) in adult black Nigerians. Methods One hundred and one subjects with office blood pressure (BP) < 140/90 mmHg were categorised according to their office BP into normotensive (BP < 120/80 mmHg, n = 57) and prehypertensive (BP 120–139/80–89 mmHg, n = 44) groups. Echocardiography and electrocardiography (ECG) were performed on the subjects. Results Thirty-four males aged 53.65 ± 16.33 years and 67 females aged 52.42 ± 12.00 years were studied. The mean QT interval dispersion (QTd) of the normotensive (38.96 ± 11.06 ms) and prehypertensive (38.41 ± 11.81 ms) groups were similar (p = 0.81). Prehypertensive subjects had higher left ventricular mass (LVM) (165.75 ± 33.21 vs 144.54 ± 35.55 g, p = 0.024), left ventricular mass index 1 (LVMI-1) (91.65 ± 16.84 vs 80.45 ± 18.65 g/m2, p = 0.021) and left ventricular mass index 2 (LVMI-2) (54.96 ± 10.84 vs 47.51 ± 12.00 g/m2.7, p = 0.017). QTd was independent of echocardiographic and electrocardiographic LVH (p > 0.05). Conclusion Compared with normotension, prehypertension is associated with higher LVM but similar QTd. This suggests that structural remodelling precedes electrical remodelling in prehypertension. PMID:24844553

  17. Intracellular recording of in situ ventricular cells during ventricular fibrillation.

    PubMed

    Akiyama, T

    1981-04-01

    Transmembrane action potentials (AP) from ventricular cells during ventricular fibrillation (VF) have not been systematically studied. We have recently developed a motion-compensated micropipette holder that holds a micropipette and moves in synchrony with heart motion. AP of subepicardial ventricular cells were recorded in 14 open-chest anesthetized dogs prior to occlusion (control) of left anterior descending artery (LAD) and during first 10 min of reperfusion-induced VF. During control, characteristics (means +/- SE) of AP are: excitation rate (R), 112 +/- 4 beats/min; resting potential (Vr), -79.3 +/- 1.0 mV; overshoot potential (Vov), 17.9 +/- 1.8 mV; 90% AP duration (APD), 251 +/- 8 ms. During VF, AP from the reperfused areas are: R, 173 +/- 27 beats/min; Vr, -60.6 +/- 2.2 mV; Vov, 3.4 +/- 2.9 mV; APD, 134 +/- 9 ms (significantly different from control at P less than 0.001, except R). During VF, cells from the reperfused areas are made inexcitable with verapamil, but not by tetrodotoxin. In conclusion, during VF accurate AP recording is possible from in situ heart, and subepicardial cells in reperfused areas seem to have AP of slow-channel type. PMID:7223899

  18. Circulating Annexin A5 Levels after Atrial Switch for Transposition of the Great Arteries: Relationship with Ventricular Deformation and Geometry

    PubMed Central

    Lai, Clare T. M.; Chow, Pak-cheong; Wong, Sophia J.; Chan, Koon-wing; Cheung, Yiu-fai

    2012-01-01

    Background Inflammatory cytokines, cardiomyocyte apoptosis, and altered collagen turnover may contribute to unfavourable ventricular remodeling. This unfavourable ventricular remodelling is well documented in patients after atrial switch operation for complete transposition of the great arteries. We therefore tested if levels of circulating markers of inflammation, apoptosis, collagen synthesis, and extracellular matrix degradation are altered in patients after atrial switch operation for transposition of the great arteries. Methods and Results Circulating tumour necrosis factor (TNF)-α, annexin A5 (AnxA5), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined in 27 patients aged 25.2±3.1 years and 20 controls. Ventricular myocardial deformation and left ventricular eccentricity index (EI) were determined by speckle tracking and two-dimensional echocardiography, respectively. Compared with controls, patients had significantly higher circulating AnxA5 (p<0.001) and TNF-α (p = 0.018) levels, but similar PICP, PIIINP, MMP-1 and TIMP-1 levels. For the whole cohort, plasma AnxA5 correlated with serum TNF-α (p = 0.002), systemic ventricular global longitudinal strain (GLS) and systolic and early diastolic strain rate (all p<0.001), and subpulmonary ventricular GLS and early diastolic strain rate (both p<0.001). In patients, plasma AnxA5 level correlated positively with subpulmonary ventricular EI (p = 0.027). Multiple linear regression analysis identified systemic ventricular GLS (β = −0.50, p<0.001) and serum TNF-α (β = 0.29, p = 0.022) as significant correlates of plasma AnxA5. Conclusions Elevated plasma AnxA5 level in patients after atrial switch operation is associated with impaired systemic myocardial deformation, increased subpulmonary ventricular

  19. Ethical challenges with the left ventricular assist device as a destination therapy

    PubMed Central

    Rizzieri, Aaron G; Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan L

    2008-01-01

    The left ventricular assist device was originally designed to be surgically implanted as a bridge to transplantation for patients with chronic end-stage heart failure. On the basis of the REMATCH trial, the US Food and Drug Administration and the US Centers for Medicare & Medicaid Services approved permanent implantation of the left ventricular assist device as a destination therapy in Medicare beneficiaries who are not candidates for heart transplantation. The use of the left ventricular assist device as a destination therapy raises certain ethical challenges. Left ventricular assist devices can prolong the survival of average recipients compared with optimal medical management of chronic end-stage heart failure. However, the overall quality of life can be adversely affected in some recipients because of serious infections, neurologic complications, and device malfunction. Left ventricular assist devices alter end-of-life trajectories. The caregivers of recipients may experience significant burden (e.g., poor physical health, depression, anxiety, and posttraumatic stress disorder) from destination therapy with left ventricular assist devices. There are also social and financial ramifications for recipients and their families. We advocate early utilization of a palliative care approach and outline prerequisite conditions so that consenting for the use of a left ventricular assist device as a destination therapy is a well informed process. These conditions include: (1) direct participation of a multidisciplinary care team, including palliative care specialists, (2) a concise plan of care for anticipated device-related complications, (3) careful surveillance and counseling for caregiver burden, (4) advance-care planning for anticipated end-of-life trajectories and timing of device deactivation, and (5) a plan to address the long-term financial burden on patients, families, and caregivers. Short-term mechanical circulatory devices (e.g. percutaneous cardiopulmonary

  20. Ventricular assist devices: initial orientation

    PubMed Central

    Dave, Hitendu; Lemme, Frithjof; Romanchenko, Olga; Hofmann, Michael; Hübler, Michael

    2013-01-01

    Ventricular assist device (VAD) technology has come from large pulsatile-flow devices with a high rate of technical malfunctions to small continuous flow (cf) devices. Mechanical circulatory support (MCS) systems may be used as short-, mid- or long-term support. Especially if mid- or long-term support is anticipated left VADs (LVADs) have been reported with excellent one and two year survival rates and improved quality of life (QoL). Timing of implantation, patient selection, assessing function of the right ventricular and surgical considerations regarding surgical access side, valve pathology and exit side of the percutaneous lead remain crucial issues for the outcome. In contrast VADs designed for children especially for all age groups, are still underrepresented but increased experience with existing pediatric VADs as well as introduction of second and third generation VADs into in the pediatric age group, offer new perspectives. PMID:23991317

  1. Dabigatran for left ventricular thrombus.

    PubMed

    Kolekar, Satishkumar; Munjewar, Chandrashekhar; Sharma, Satyavan

    2015-01-01

    Male patient in dilated phase of hypertrophic cardiomyopathy had multiple hospitalizations during the past 2 years either due to congestive heart failure, stroke, scar epilepsy, or atrial fibrillation and ventricular tachycardia. Medication included evidence based therapy for heart failure, cordarone and warfarin. Anticoagulation had to be discontinued due to marked fluctuations in INR. Transthoracic Echocardiography (TTE) revealed a mobile mass in the left ventricle. He was treated with Dabigatran 110mg twice a day for 4 months without any bleeding or embolic episode and complete resolution of thrombus. Dabigatran is a reversible direct thrombin inhibitor and currently approved for the prevention of thromboembolic episodes in non-valvar atrial fibrillation. This case demonstrates possible thrombolytic properties of dabigatran in resolution of left ventricular thrombus. PMID:26432747

  2. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

    There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin. PMID:6995091

  3. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR. PMID:19967009

  4. Significance of Late Gadolinium Enhancement at Right Ventricular Attachment to Ventricular Septum in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Chan, Raymond H; Maron, Barry J; Olivotto, Iacopo; Assenza, Gabriele E; Haas, Tammy S; Lesser, John R; Gruner, Christiane; Crean, Andrew M; Rakowski, Harry; Rowin, Ethan; Udelson, James; Lombardi, Massimo; Tomberli, Benedetta; Spirito, Paolo; Formisano, Francesco; Marra, Martina P; Biagini, Elena; Autore, Camillo; Manning, Warren J; Appelbaum, Evan; Roberts, William C; Basso, Cristina; Maron, Martin S

    2015-08-01

    Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death (SD) in patients with hypertrophic cardiomyopathy (HC). Small focal areas of LGE confined to the region of right ventricular (RV) insertion to ventricular septum (VS) have emerged as a frequent and highly visible CMR imaging pattern of uncertain significance. The aim of this study was to evaluate the prognostic significance of LGE confined to the RV insertion area in patients with HC. CMR was performed in 1,293 consecutive patients with HC from 7 HC centers, followed for 3.4 ± 1.7 years. Of 1,293 patients (47 ± 14 years), 134 (10%) had LGE present only in the anterior and/or inferior areas of the RV insertion to VS, occupying 3.7 ± 2.9% of left ventricular myocardium. Neither the presence nor extent of LGE in these isolated areas was a predictor of adverse HC-related risk, including SD (adjusted hazard ratio 0.82, 95% confidence interval 0.45 to 1.50, p = 0.53; adjusted hazard ratio 1.16/10% increase in LGE, 95% confidence interval 0.29 to 4.65, p = 0.83, respectively). Histopathology in 20 HC hearts show the insertion areas of RV attachment to be composed of a greatly expanded extracellular space characterized predominantly by interstitial-type fibrosis and interspersed disorganized myocyte patterns and architecture. In conclusion, LGE confined to the insertion areas of RV to VS was associated with low risk of adverse events (including SD). Gadolinium pooling in this region of the left ventricle does not reflect myocyte death and repair with replacement fibrosis or scarring. PMID:26026863

  5. Echocardiographic Predictors of Ventricular Tachycardia

    PubMed Central

    Catanzaro, John N; Makaryus, John N; Makaryus, Amgad N; Sison, Cristina; Vavasis, Christos; Fan, Dali; Jadonath, Ram

    2014-01-01

    BACKGROUND Patients with structural heart disease are prone to ventricular tachycardia (VT) and ventricular fibrillation (VF), which account for the majority of sudden cardiac deaths (SCDs). We sought to examine echocardiographic parameters that can predict VT as documented by implantable cardioverter-defibrillator (ICD) appropriate discharge. We examine echocardiographic parameters other than ejection fraction that may predict VT as recorded via rates of ICD discharge. METHODS Analysis of 586 patients (469 males; mean age = 68 ± 3 years; mean follow-up time of 11 ± 14 months) was undertaken. Echo parameters assessed included left ventricular (LV) internal end diastolic/systolic dimension (LVIDd, LVIDs), relative wall thickness (RWT), and left atrial (LA) size. RESULTS The incidence of VT was 0.22 (114 VT episodes per 528 person-years of follow-up time). Median time-to-first VT was 3.8 years. VT was documented in 79 patients (59 first VT incidence, 20 multiple). The echocardiographic parameter associated with first VT was LVIDs >4 cm (P = 0.02). CONCLUSION The main echocardiographic predictor associated with the first occurrence of VT was LVIDs >4 cm. Patients with an LVIDs >4 cm were 2.5 times more likely to have an episode of VT. Changes in these echocardiographic parameters may warrant aggressive pharmacologic therapy and implantation of an ICD. PMID:25861227

  6. [THE RELATIONSHIP BETWEEN DISORDERS-OF EXTERNAL RESPIRATION AND RIGHT HEART REMODELING IN PATIENTS WITH ATOPIC BRONCHIAL ASTHMA].

    PubMed

    Solov'eva, I A; Sobko, E A; Ryazanova, N G; Krapohsina, A Yu; Gorgeeva, N V; Demko, I V

    2015-01-01

    This study aimed at the evaluation of the state of the respiratory system and its possible influence on the structural and functional characteristics of the right heart in patients with atopic bronchial asthma (BA) with a view to optimizing diagnostics and prevention of cardiovascular complications. The study included 189 subjects of whom 148 with BA were divided into 3 groups depending on the severity of the disease. Forty practically healthy volunteers comprised the control group. The external respiration function and right ventricle functional parameters were the main variables measured in all the participants of the study. It was shown that disorders of external respiration and pulmonary hyperinflation progressed with severity of BA and thereby promoted right ventricular myocardium remodeling and dysfunction that in turn led to chronic cardiac insufficiency. It is concluded that functional changes in the right heart in of patients with BA of different severity are associated with remodeling of the respiratory tract. PMID:26964462

  7. Obesity and carotid artery remodeling

    PubMed Central

    Kozakova, M; Palombo, C; Morizzo, C; Højlund, K; Hatunic, M; Balkau, B; Nilsson, P M; Ferrannini, E

    2015-01-01

    Background/Objective: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions characterized by body size-dependent increase in stroke volume (SV) and blood pressure (BP). Subjects/Methods: Common carotid artery (CCA) luminal diameter (LD), IMT and CWS were measured in three different populations in order to study: (A) cross-sectional associations between SV, BP, anthropometric parameters and CCA LD (266 healthy subjects with wide range of body weight (24–159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects without CV complications and 88 non-obese subjects matched for gender and age). Results: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was significantly higher (28±3 μm) as compared with those in the lower quartiles (8±3, 16±4 and 16±3 μm, P=0.001, P<0.05 and P=0.01, respectively). In addition, CCA CWS decreased during the observational period in the highest LD quartile (from 54.2±8.6 to 51.6±7.4 kPa, P<0.0001). As compared with gender- and age-matched lean individuals, obese subjects had highly increased CCA LD and BP (P<0.0001 for both), but only slightly higher CWS (P=0.05) due to a significant increase in IMT (P=0.005 after adjustment for confounders). Conclusions: Our findings suggest that in obese subjects, the CCA wall thickens to compensate the luminal enlargement caused by body size-induced increase in SV, and therefore, to normalize the wall stress. CCA diameter in obesity could

  8. Electrotonic remodeling following myocardial infarction in dogs susceptible and resistant to sudden cardiac death.

    PubMed

    Del Rio, Carlos L; McConnell, Patrick I; Kukielka, Monica; Dzwonczyk, Roger; Clymer, Bradley D; Howie, Michael B; Billman, George E

    2008-02-01

    Passive electrical remodeling following myocardial infarction (MI) is well established. These changes can alter electrotonic loading and trigger the remodeling of repolarization currents, a potential mechanism for ventricular fibrillation (VF). However, little is known about the role of passive electrical markers as tools to identify VF susceptibility post-MI. This study investigated electrotonic remodeling in the post-MI ventricle, as measured by myocardial electrical impedance (MEI), in animals prone to and resistant to VF. MI was induced in dogs by a two-stage left anterior descending (LAD) coronary artery ligation. Before infarction, MEI electrodes were placed in remote (left circumflex, LCX) and infarcted (LAD) myocardium. MEI was measured in awake animals 1, 2, 7, and 21 days post-MI. Subsequently, VF susceptibility was tested by a 2-min LCX occlusion during exercise; 12 animals developed VF (susceptible, S) and 12 did not (resistant, R). The healing infarct had lower MEI than the normal myocardium. This difference was stable by day 2 post-MI (287 +/- 32 Omega vs. 425 +/- 62 Omega, P < 0.05). Significant differences were observed between resistant and susceptible animals 7 days post-MI; susceptible dogs had a wider electrotonic gradient between remote and infarcted myocardium (R: 89 +/- 60 Omega vs. S: 180 +/- 37 Omega). This difference increased over time in susceptible animals (252 +/- 53 Omega at 21 days) due to post-MI impedance changes on the remote myocardium. These data suggest that early electrotonic changes post-MI could be used to assess later arrhythmia susceptibility. In addition, passive-electrical changes could be a mechanism driving active-electrical remodeling post-MI, thereby facilitating the induction of arrhythmias. PMID:18048585

  9. Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model

    PubMed Central

    Chen, Yu-cai; Yuan, Tian-yi; Zhang, Hui-fang; Wang, Dan-shu; Yan, Yu; Niu, Zi-ran; Lin, Yi-huang; Fang, Lian-hua; Du, Guan-hua

    2016-01-01

    Aim: The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg−1·d−1) or a positive control bosentan (30 mg·kg−1·d−1) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Results: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. Conclusion: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH. PMID:27180980

  10. Oral administration of veratric acid, a constituent of vegetables and fruits, prevents cardiovascular remodelling in hypertensive rats: a functional evaluation.

    PubMed

    Saravanakumar, Murugesan; Raja, Boobalan; Manivannan, Jeganathan; Silambarasan, Thangarasu; Prahalathan, Pichavaram; Kumar, Subramanian; Mishra, Santosh Kumar

    2015-11-14

    In our previous studies, veratric acid (VA) shows beneficial effect on hypertension and its associated dyslipidaemia. In continuation, this study was designed to investigate the effect of VA, one of the major benzoic acid derivatives from vegetables and fruits, on cardiovascular remodelling in hypertensive rats, primarily assessed by functional studies using Langendorff isolated heart system and organ bath system. Hypertension was induced in male albino Wistar rats by oral administration of N ω -nitro-l-arginine methyl ester hydrochloride (l-NAME) (40 mg/kg body weight (b.w.)) in drinking water for 4 weeks. VA was orally administered at a dose of 40 mg/kg b.w. l-NAME-treated rats showed impaired cardiac ventricular and vascular function, evaluated by Langendorff isolated heart system and organ bath studies, respectively; a significant increase in the lipid peroxidation products such as thiobarbituric acid-reactive substances and lipid hydroperoxides in aorta; and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and levels of GSH, vitamin C and vitamin E in aorta. Fibrotic remodelling of the aorta and heart were assessed by Masson's Trichrome staining and Van Gieson's staining, respectively. In addition, l-NAME rats showed increased heart fibronectin expression assessed by immunohistochemical analysis. VA supplementation throughout the experimental period significantly normalised cardiovascular function, oxidative stress, antioxidant status and fibrotic remodelling of tissues. These results of the present study conclude that VA acts as a protective agent against hypertension-associated cardiovascular remodelling. PMID:26346559

  11. A fly's view of neuronal remodeling.

    PubMed

    Yaniv, Shiri P; Schuldiner, Oren

    2016-09-01

    Developmental neuronal remodeling is a crucial step in sculpting the final and mature brain connectivity in both vertebrates and invertebrates. Remodeling includes degenerative events, such as neurite pruning, that may be followed by regeneration to form novel connections during normal development. Drosophila provides an excellent model to study both steps of remodeling since its nervous system undergoes massive and stereotypic remodeling during metamorphosis. Although pruning has been widely studied, our knowledge of the molecular and cellular mechanisms is far from complete. Our understanding of the processes underlying regrowth is even more fragmentary. In this review, we discuss recent progress by focusing on three groups of neurons that undergo stereotypic pruning and regrowth during metamorphosis, the mushroom body γ neurons, the dendritic arborization neurons and the crustacean cardioactive peptide peptidergic neurons. By comparing and contrasting the mechanisms involved in remodeling of these three neuronal types, we highlight the common themes and differences as well as raise key questions for future investigation in the field. WIREs Dev Biol 2016, 5:618-635. doi: 10.1002/wdev.241 For further resources related to this article, please visit the WIREs website. PMID:27351747

  12. The role of midkine in skeletal remodelling

    PubMed Central

    Liedert, A; Schinke, T; Ignatius, A; Amling, M

    2014-01-01

    Bone tissue is subjected to continuous remodelling, replacing old or damaged bone throughout life. In bone remodelling, the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts ensure the maintenance of bone mass and strength. In early life, the balance of these cellular activities is tightly regulated by various factors, including systemic hormones, the mechanical environment and locally released growth factors. Age-related changes in the activity of these factors in bone remodelling can result in diseases with low bone mass, such as osteoporosis. Osteoporosis is a systemic and age-related skeletal disease characterized by low bone mass and structural degeneration of bone tissue, predisposing the patient to an increased fracture risk. The growth factor midkine (Mdk) plays a key role in bone remodelling and it is expressed during bone formation and fracture repair. Using a mouse deficient in Mdk, our group have identified this protein as a negative regulator of bone formation and mechanically induced bone remodelling. Thus, specific Mdk antagonists might represent a therapeutic option for diseases characterized by low bone mass, such as osteoporosis. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:24102259

  13. Moderate Physical Activity in Healthy Adults Is Associated With Cardiac Remodeling

    PubMed Central

    Dawes, Timothy J.W.; Corden, Ben; Cotter, Sorcha; de Marvao, Antonio; Walsh, Roddy; Ware, James S.; Cook, Stuart A.

    2016-01-01

    Background— Cardiac mass and volumes are often elevated in athletes, but it is not known whether moderate physical activity is also associated with cardiac dilatation and hypertrophy in a healthy adult population. Methods and Results— In total, 1096 adults (54% female, median age 39 years) without cardiovascular disease or cardiomyopathy-associated genetic variants underwent cardiac magnetic resonance imaging to determine biventricular volumes and function. Physical activity was assessed using a validated activity questionnaire. The relationship between cardiac parameters and activity was assessed using multiple linear regression adjusting for age, sex, race, and systolic blood pressure. Logistic regression was performed to determine the effect of activity on the likelihood of subjects having cardiac dilatation or hypertrophy according to standard cardiac magnetic resonance normal ranges. Increasing physical activity was associated with greater left ventricular (LV) mass (β=0.23; P<0.0001) and elevated LV and right ventricular volumes (LV: β=0.26, P<0.0001; right ventricular: β=0.26, P<0.0001). Physical activity had a larger effect on cardiac parameters than systolic blood pressure (0.06≤β≤0.21) and a similar effect to age (−0.20≤β≤−0.31). Increasing physical activity was a risk factor for meeting imaging criteria for LV hypertrophy (adjusted odds ratio 2.1; P<0.0001), LV dilatation (adjusted odds ratio 2.2; P<0.0001), and right ventricular dilatation (adjusted odds ratio 2.2; P<0.0001). Conclusions— Exercise-related cardiac remodeling is not confined to athletes, and there is a risk of overdiagnosing cardiac dilatation or hypertrophy in a proportion of active, healthy adults. PMID:27502059

  14. Practical applicability of landiolol, an ultra-short-acting β1-selective blocker, for rapid atrial and ventricular tachyarrhythmias with left ventricular dysfunction

    PubMed Central

    Wada, Yuko; Aiba, Takeshi; Tsujita, Yasuyuki; Itoh, Hideki; Wada, Mitsuru; Nakajima, Ikutaro; Ishibashi, Kohei; Okamura, Hideo; Miyamoto, Koji; Noda, Takashi; Sugano, Yasuo; Kanzaki, Hideaki; Anzai, Toshihisa; Kusano, Kengo; Yasuda, Satoshi; Horie, Minoru; Ogawa, Hisao

    2015-01-01

    Background Landiolol effectively controls rapid heart rate in atrial fibrillation or flutter (AF/AFL) patients with left ventricular (LV) dysfunction. However, predicting landiolol Responders and Non-Responders and patients who will experience adverse effects remains a challenge. The aim of this study was to clarify the potential applicability of landiolol for rapid AF/AFL and refractory ventricular tachyarrhythmias (VTs) in patients with heart failure. Methods A total of 39 patients with AF/AFL with ventricular response ≥120 bpm and 12 VTs were retrospectively enrolled. Landiolol Responders for rapid AF/AFL were defined as patients whose ventricular response was suppressed to less than 110 bpm or decreased by ≥20% from the initial heart rate after administration of landiolol. Responders for VTs were defined as patients with no recurrent VTs during the 24 h after the initiation of landiolol. Results For AF/AFL, 29 patients (74%) were Responders. In nine patients (31%), AF was spontaneously terminated after starting landiolol. Eight Non-Responders (80%) needed to have AF terminated by cardioversion. Left ventricular ejection fraction (LVEF) at baseline was significantly associated with landiolol efficacy. For VTs, seven patients (58%) were Responders, and smaller LV diastolic and systolic diameters were associated with landiolol efficacy. Hypotension after landiolol treatment occurred in 5 of 51 patients, and lower LV systolic function was associated with the development of adverse events. Conclusions Landiolol is effective in patients with heart failure not only due to rapid AF/AFL but also due to VTs. However, preserved LVEF is important for efficacy and safety in landiolol treatment. PMID:27092187

  15. Left ventricular pseudoaneurysm after reimplantation procedure.

    PubMed

    Inoue, Takahiro; Hashimoto, Kazuhiro; Sakamoto, Yoshimasa; Yoshitake, Michio; Matsumura, Yoko; Kinami, Hiroo; Takagi, Tomomitsu

    2016-04-01

    Postoperative left ventricular pseudoaneurysm is a rare, but potentially lethal, complication because of the high risk of rupture and high mortality of repair. We report a 64-year-old man with Marfan syndrome who underwent the reimplantation valve-sparing aortic root replacement complicated by a postoperative left ventricular pseudoaneurysm that required urgent repair. Careful handling of the aortic root is required to avoid a left ventricular pseudoaneurysm, particularly in patients with connective tissue disorder. PMID:24917204

  16. Scar remodeling after strabismus surgery.

    PubMed Central

    Ludwig, I H

    1999-01-01

    limitation of versions, less separation of the tendons from sclera, and thicker appearance of the scar segments. The use of nonabsorbable sutures in the repair procedure reduced the recurrence rate. Histologic examination of the clinical stretched scar specimens showed dense connective tissue that was less well organized compared with normal tendon. In the tissue culture studies, cells cultured from the stretched scar specimens grew rapidly and were irregularly shaped. A high-molecular-weight protein was identified in the culture medium. By contrast, cells cultured from normal tendon (controls) grew more slowly and regularly, stopped growing at 4 days, and produced less total protein than cultured stretched scar specimens. In the animal model studies, the collagenase-treated sites showed elongated scars with increased collagen between the muscle and the sclera, as well as increased collagen creep rates, compared with the saline-treated controls. The use of nonabsorbable sutures in collagenase-treated animal model surgery sites was associated with shorter, thicker scars compared with similar sites sutured with absorbable sutures. CONCLUSIONS: A lengthened or stretched, remodeled scar between an operated muscle tendon and sclera is a common occurrence and is a factor contributing to the variability of outcome after strabismus repair, even years later. This abnormality may be revealed by careful exploration of previously operated muscles. Definitive repair requires firm reattachment of tendon to sclera with nonabsorbable suture support. Images FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 FIGURE 20 FIGURE 21 FIGURE 22 FIGURE 23 FIGURE 24 FIGURE 25 FIGURE 26 FIGURE 27 FIGURE 28 FIGURE 29 FIGURE 30 FIGURE 31 FIGURE 32 FIGURE 33 FIGURE 34 FIGURE 35 FIGURE 36 FIGURE 37 FIGURE 38 FIGURE 39 FIGURE 40 FIGURE 41 FIGURE 42 FIGURE 43 FIGURE 44 FIGURE 45 FIGURE 46 FIGURE 52

  17. Ventricular dilatation in the absence of ACE inhibitors: influence of haemodynamic and neurohormonal variables following myocardial infarction

    PubMed Central

    Walsh, J; Batin, P; Hawkins, M; McEntegart, D; Cowley, A

    1999-01-01

    Objective—To examine the relation between patterns of ventricular remodelling and haemodynamic and neurohormonal variables, at rest and during symptom limited exercise, in the year following acute myocardial infarction in patients not receiving angiotensin converting enzyme (ACE) inhibitors.
Design—A prospective observational study.
Patients—65 patients recruited following hospital admission with a transmural anterior myocardial infarction.
Methods—Central haemodynamics and neurohormonal activation at rest and during symptom limited treadmill exercise were measured at baseline before hospital discharge, one month later, and at three monthly intervals thereafter. Patients were classified according to individual patterns of change in left ventricular end diastolic volumes at rest, assessed at each visit using transthoracic echocardiography.
Results—In most patients (n = 43, 66%) ventricular volumes were unchanged or reduced. Mean (SEM) treadmill exercise capacity and peak exercise cardiac index increased at month 12 by 200 (24) seconds (p < 0.001 v baseline) and by 0.8 (0.4) l/min/m2 (p<0.05 v baseline), respectively, in this group. In patients with limited ventricular dilatation (n = 11, 17%) exercise capacity increased by 259 (52) seconds (p < 0.001 v baseline) and peak exercise cardiac index improved by 0.8 (0.7) l/min/m2 (NS). In the remaining 11 patients with progressive left ventricular dilatation, exercise capacity increased by 308 (53) seconds (p< 0.001 v baseline) and peak exercise cardiac index similarly improved by 1.3 (0.7) l/min/m2 (NS). There were trends towards increased atrial natriuretic factor (ANF) secretion at rest and at peak exercise in this group.
Conclusions—Ventricular dilatation after acute myocardial infarction is a heterogeneous process that is progressive in only a minority of patients. Compensatory mechanisms, including ANF release, appear capable of maintaining and improving exercise capacity in

  18. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  19. Right ventricular failure after left ventricular assist devices.

    PubMed

    Lampert, Brent C; Teuteberg, Jeffrey J

    2015-09-01

    Most patients with advanced systolic dysfunction who are assessed for a left ventricular assist device (LVAD) also have some degree of right ventricular (RV) dysfunction. Hence, RV failure (RVF) remains a common complication of LVAD placement. Severe RVF after LVAD implantation is associated with increased peri-operative mortality and length of stay and can lead to coagulopathy, altered drug metabolism, worsening nutritional status, diuretic resistance, and poor quality of life. However, current medical and surgical treatment options for RVF are limited and often result in significant impairments in quality of life. There has been continuing interest in developing risk models for RVF before LVAD implantation. This report reviews the anatomy and physiology of the RV and how it changes in the setting of LVAD support. We will discuss proposed mechanisms and describe biochemical, echocardiographic, and hemodynamic predictors of RVF in LVAD patients. We will describe management strategies for reducing and managing RVF. Finally, we will discuss the increasingly recognized and difficult to manage entity of chronic RVF after LVAD placement and describe opportunities for future research. PMID:26267741

  20. Prospective study of left ventricular function after radiofrequency ablation of atrioventricular junction in patients with atrial fibrillation.

    PubMed Central

    Edner, M.; Caidahl, K.; Bergfeldt, L.; Darpö, B.; Edvardsson, N.; Rosenqvist, M.

    1995-01-01

    BACKGROUND--In patients with drug resistant incessant supraventricular tachycardia, radiofrequency induced ablation of the atrioventricular junction and pacemaker implantation have hitherto been considered a treatment of last resort. OBJECTIVE--To assess the short and long term effects of ablation of the atrioventricular junction on systolic and diastolic left ventricular function in patients with atrial fibrillation with and without impaired left ventricular function. PATIENTS--29 patients (19 men; mean age 65 (SD 7) years (range 50-76)) undergoing ablation of the atrioventricular junction for drug refractory atrial fibrillation were examined a mean of 2, 65, and 216 days after ablation of the bundle of His. MAIN OUTCOME MEASURES--Left ventricular ejection fraction and early filling deceleration times (Edec) were assessed by Doppler echocardiography after 1 to 2 hours of ventricular pacing at a rate of 80 beats/minute. RESULTS--In 14 patients with a left ventricular ejection fraction < 50% left ventricular ejection fraction increased significantly from 32% (11%) to 39% (11%) (65 days) and 45% (11%) (216 days) (P < 0.001); Edec increased from 142 (46) ms to 169 (57) ms (65 days) and 167 (56) ms (216 days) (P < 0.05). In 15 patients with an ejection fraction > or = 50% at the initial examination no significant change in systolic function was observed. CONCLUSIONS--In patients with left ventricular dysfunction long term improvement of systolic and diastolic left ventricular function was seen after ablation of the atrioventricular junction for rate control of atrial fibrillation. This procedure had no adverse effects on normal left ventricular function. PMID:7547020

  1. Reverse remodeling and recovery from cachexia in rats with aldosteronism.

    PubMed

    Cheema, Yaser; Zhao, Wenyuan; Zhao, Tieqiang; Khan, M Usman; Green, Kelly D; Ahokas, Robert A; Gerling, Ivan C; Bhattacharya, Syamal K; Weber, Karl T

    2012-08-15

    The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca(2+), coupled to oxidative stress with increased H(2)O(2) production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal. PMID:22730385

  2. Reverse remodeling and recovery from cachexia in rats with aldosteronism

    PubMed Central

    Cheema, Yaser; Zhao, Wenyuan; Zhao, Tieqiang; Khan, M. Usman; Green, Kelly D.; Ahokas, Robert A.; Gerling, Ivan C.; Bhattacharya, Syamal K.

    2012-01-01

    The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca2+, coupled to oxidative stress with increased H2O2 production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal. PMID:22730385

  3. Idiopathic left ventricular apical hypoplasia.

    PubMed

    Raza, Ali; Waleed, Mohammad; Balerdi, Matthew; Bragadeesh, Thanjavur; Clark, Andrew L

    2014-01-01

    A 46-year-old man was found to have an abnormal ECG taken during a routine health and blood pressure check. His only symptom was non-specific central chest discomfort, unrelated to exertion. His ECG showed sinus rhythm, a normal axis and poor R wave progression across the chest leads and lateral T wave flattening. An echocardiogram showed a dilated left ventricle with a thin and hypokinetic septum bulging to the right. The apex was 'not well seen' but also appeared thin and hypokinetic. The right heart and valves were normal. The patient was further investigated for left ventricular hypoplasia. PMID:24585345

  4. Epicardial Ablation For Ventricular Tachycardia

    PubMed Central

    Maccabelli, Giuseppe; Mizuno, Hiroya; Della Bella, Paolo

    2012-01-01

    Epicardial ablation has lately become a necessary tool to approach some ventricular tachycardias in different types of cardiomyopathy. Its diffusion is now limited to a few high volume centers not because of the difficulty of the pericardial puncture but since it requires high competence not only in the VT ablation field but also in knowing and recognizing the possible complications each of which require a careful treatment. This article will review the state of the art of epicardial ablation with special attention to the procedural aspects and to the possible selection criteria of the patients PMID:23233758

  5. Right Ventricular Outflow Tract Tachycardia with Structural Abnormalities of the Right Ventricle and Left Ventricular Diverticulum

    PubMed Central

    Martini, Bortolo; Trevisi, Nicola; Martini, Nicolò; Zhang, Li

    2015-01-01

    A 43-year-old woman presented to the emergency room with a sustained ventricular tachycardia (VT). ECG showed a QRS in left bundle branch block morphology with inferior axis. Echocardiography, ventricular angiography, and cardiac magnetic resonance imaging (CMRI) revealed a normal right ventricle and a left ventricular diverticulum. Electrophysiology studies with epicardial voltage mapping identified a large fibrotic area in the inferolateral layer of the right ventricular wall and a small area of fibrotic tissue at the anterior right ventricular outflow tract. VT ablation was successfully performed with combined epicardial and endocardial approaches. PMID:26509086

  6. Outflow Tract Premature Ventricular Contractions and Ventricular Tachycardia: The Typical and the Challenging.

    PubMed

    John, Roy M; Stevenson, William G

    2016-09-01

    The ventricular outflow tracts are the most common sites of origin for ventricular arrhythmias that occur in the absence of structural heart disease. Drug therapy with β-blockers and calcium blockers has limited efficacy for control. In the presence of marked symptoms or frequent arrhythmia causing left ventricular (LV) dysfunction, catheter ablation is a consideration. The right ventricular outflow tract, aortic root, LV outflow endocardium, and epicardium are potential sites for ablation for these arrhythmias. In intractable cases of highly symptomatic ventricular arrhythmias originating from the LV summit, surgical ablation is an option. PMID:27521088

  7. Physical Activity and Right Ventricular Structure and Function

    PubMed Central

    Aaron, Carrie P.; Tandri, Harikrishna; Barr, R. Graham; Johnson, W. Craig; Bagiella, Emilia; Chahal, Harjit; Jain, Aditya; Kizer, Jorge R.; Bertoni, Alain G.; Lima, João A. C.; Bluemke, David A.; Kawut, Steven M.

    2011-01-01

    Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown. Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent–minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity. Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes. Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications. PMID:20813888

  8. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    SciTech Connect

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  9. Hyperpulsatile pressure, systemic inflammation and cardiac stress are associated with cardiac wall remodeling in an African male cohort: the SABPA study.

    PubMed

    van Vuren, Esmé Jansen; Malan, Leoné; von Känel, Roland; Cockeran, Marike; Malan, Nicolaas T

    2016-09-01

    Inflammation may contribute to an increase in cardiac wall stress through pathways related to cardiac remodeling. Cardiac remodeling is characterized by myocyte hypertrophy, myocyte death and modifications of the extracellular matrix. We sought to explore associations among cardiac remodeling, inflammation and myocardial cell injury in a bi-ethnic cohort of South African men and women. We included 165 men (76 African and 89 Caucasian) and 174 women (80 African and 94 Caucasian) between 20 and 65 years of age. Inflammatory markers used were C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-α), whereas troponin T (Trop T) and the N-terminal of pro B-type natriuretic peptide (NT-proBNP) were used as cardiac markers. The frequency of ischemic events (ST segment depression) and left ventricular strain (left ventricular hypertrophy: LVH) were monitored by a 24-h recording of ambulatory blood pressure (BP), ECG and 12-lead standard ECG. Hypertension diagnosed with ambulatory monitoring was more frequent in Africans (53.85 vs. 24.59%; P<0.001), as was the number of ischemic events (6±15 (1; 5) vs. 3±6 (0; 3)). Inflammatory markers (CRP, IL-6 and TNF-α) and the degree of LVH were all significantly higher in Africans (P<0.05). BP was associated (P<0.05) with Trop T in men across ethnic groups. In African men, cardiac stress (NT-proBNP) was associated with TNF-alpha (P<0.001), Trop T (P<0.001) and pulse pressure (P=0.048; adjusted R(2)=0.45). The susceptibility for cardiac wall remodeling appears to increase with hyperpulsatile pressure, low-grade systemic inflammation and ventricular stress, and may lead to the development of future cardiovascular events in African men. PMID:27169396

  10. Ventricular-Fold Dynamics in Human Phonation

    ERIC Educational Resources Information Center

    Bailly, Lucie; Bernardoni, Nathalie Henrich; Müller, Frank; Rohlfs, Anna-Katharina; Hess, Markus

    2014-01-01

    Purpose: In this study, the authors aimed (a) to provide a classification of the ventricular-fold dynamics during voicing, (b) to study the aerodynamic impact of these motions on vocal-fold vibrations, and (c) to assess whether ventricular-fold oscillations could be sustained by aerodynamic coupling with the vocal folds. Method: A 72-sample…

  11. An Unusual Etiology for Bidirectional Ventricular Tachycardia.

    PubMed

    Zhao, Yun-Tao; Wang, Lei; Yi, Zhong

    2016-03-01

    Bidirectional ventricular tachycardia is a rare variety of tachycardia with a morphologically distinct presentation. The QRS axis and/or morphology alternate in the frontal plane leads. We report a patient with bidirectional ventricular tachycardia in association with aconitine poisoning. PMID:26604120

  12. Bidirectional ventricular tachycardia of unusual etiology

    PubMed Central

    Chakraborty, Praloy; Kaul, Bhavna; Mandal, Kausik; Isser, H.S.; Bansal, Sandeep; Subramanian, Anandaraja

    2016-01-01

    Bidirectional ventricular tachycardia (BDVT) is a rare form of ventricular arrhythmia, characterized by changing QRS axis of 180 degrees. Digitalis toxicity is considered as commonest cause of BDVT; other causes include aconite toxicity, myocarditis, myocardial infarction, metastatic cardiac tumour and cardiac channelopathies. We describe a case of BDVT in a patient with Anderson-Tawil syndrome.

  13. 21 CFR 882.4060 - Ventricular cannula.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ventricular cannula. 882.4060 Section 882.4060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Identification. A ventricular cannula is a device used to puncture the ventricles of the brain for aspiration...

  14. 21 CFR 882.4060 - Ventricular cannula.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ventricular cannula. 882.4060 Section 882.4060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Identification. A ventricular cannula is a device used to puncture the ventricles of the brain for aspiration...

  15. 21 CFR 882.4060 - Ventricular cannula.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ventricular cannula. 882.4060 Section 882.4060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Identification. A ventricular cannula is a device used to puncture the ventricles of the brain for aspiration...

  16. 21 CFR 882.4060 - Ventricular cannula.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ventricular cannula. 882.4060 Section 882.4060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Identification. A ventricular cannula is a device used to puncture the ventricles of the brain for aspiration...

  17. 21 CFR 882.4060 - Ventricular cannula.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ventricular cannula. 882.4060 Section 882.4060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Identification. A ventricular cannula is a device used to puncture the ventricles of the brain for aspiration...

  18. What Is a Ventricular Assist Device?

    MedlinePlus

    ... basic types of VADs are a left ventricular assist device (LVAD) and a right ventricular assist device (RVAD). If both types are used at the same time, they're called a biventricular assist device (BIVAD). The LVAD is the most common type of VAD. It ...

  19. Subdural hygroma after craniosynostosis remodeling surgery.

    PubMed

    Ganesh, Praveen; Nagarjuna, Muralidhara; Shetty, Samarth; Salins, Paul C

    2015-01-01

    Craniosynostosis is defined as the premature fusion of the cranial sutures and can cause functional impairment or cosmetic deformity. Surgical techniques for the correction of craniosynostosis have changed overtime, as so have the intraoperative and postoperative complications. Extensive surgeries involving fronto-orbital unit repositioning and cranial vault remodeling are associated with various complications. Intraoperative and postoperative hemorrhage, venous infarct, air embolism, hydrocephalus, cerebrospinal fluid leak, as well as meningitis are a few complications associated with cranial vault remodeling surgery. Postoperative complications can increase the morbidity and mortality associated with these procedures. Identification of the complications and their timely management should be a part of every craniofacial reconstruction team's training program.In this article, we report a case of subdural hygroma in an infant after cranial vault remodeling procedure. Subdural hygroma is a known complication following head injuries and represents 5% to 20% of posttraumatic intracranial mass lesions. However, subdural hygroma developing after a cranial procedure is rare and has not been reported in the literature. Identification of the complication, close monitoring of the change in subdural fluid volume, and tapping of the fluid through the craniotomy site if indicated form the mainstay of management of subdural hygroma that develops after cranial vault remodeling surgery. PMID:25469899

  20. Interleukin-20 promotes airway remodeling in asthma.

    PubMed

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

  1. Chromatin-modifying and -remodeling complexes.

    PubMed

    Kornberg, R D; Lorch, Y

    1999-04-01

    Nucleosomes have long been known to inhibit DNA transactions on chromosomes and a remarkable abundance of multiprotein complexes that either enhance or relieve this inhibition have been described. Most is known about chromatin-remodeling complexes that perturb nucleosome structure. PMID:10322131

  2. Challenging Modernization: Remodelling the Education Workforce

    ERIC Educational Resources Information Center

    Butt, Graham; Gunter, Helen

    2005-01-01

    This special edition enables an in-depth look at the process of modernization of education in England, in relation to other international developments. In particular we focus on the reform of teachers? work by examining the antecedence of the current policy of remodelling through three articles based on the Evaluation of the Department for…

  3. Re-Modelling as De-Professionalisation

    ERIC Educational Resources Information Center

    Thompson, Meryl

    2006-01-01

    The article sets out the consequences of the British Government's remodelling agenda and its emphasis on less demarcation, for the professional status of teachers in England. It describes how the National Agreement on Raising Standards and Tackling Workload, reached between five of the six trade unions for teachers and headteachers paves the way…

  4. Arterial Remodeling Associates with CKD Progression

    PubMed Central

    Collin, Cédric; Karras, Alexandre; Laurent, Stéphane; Bozec, Erwan; Jacquot, Christian; Stengel, Bénédicte; Houillier, Pascal; Froissart, Marc; Boutouyrie, Pierre

    2011-01-01

    In CKD, large arteries remodel and become increasingly stiff. The greater pulsatile pressure reaching the glomerulus as a result of increased aortic stiffness could induce renal damage, suggesting that the stiffening and remodeling of large arteries could affect the progression of CKD. We measured carotid-femoral pulse wave velocity, aortic pressure and carotid remodeling and stiffness parameters in 180 patients with CKD (mean measured GFR, 32 ml/min per 1.73 m2) and followed them prospectively for a mean of 3.1 years. During follow-up, carotid stiffness significantly increased (+0.28 ± 0.05 m/s; P < 0.0001) but aortic stiffness did not. Carotid intima-media thickness decreased significantly during follow-up and the internal diameter of the carotid increased, producing increased circumferential wall stress (+2.08 ± 0.43 kPa/yr; P < 0.0001). In a linear mixed model, circumferential wall stress significantly associated with faster GFR decline after adjustment for risk factors of cardiovascular disease and progression of CKD. In a multivariable Cox model, carotid circumferential wall stress and pulse pressure independently associated with higher risk for ESRD. None of the arterial stiffness parameters associated with progression of CKD. In conclusion, maladaptive remodeling of the carotid artery and increased pulse pressure independently associate with faster decline of renal function and progression to ESRD. PMID:21493771

  5. Revealing remodeler function: Varied and unique

    NASA Astrophysics Data System (ADS)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  6. New therapy, new challenges: The effects of long-term continuous flow left ventricular assist device on inflammation.

    PubMed

    Grosman-Rimon, Liza; Billia, Filio; Fuks, Avi; Jacobs, Ira; A McDonald, Michael; Cherney, David Z; Rao, Vivek

    2016-07-15

    Surgically implanted continuous flow left ventricular assist devices (CF-LVADs) are currently used in patients with end-stage heart failure (HF). However, CF-LVAD therapy introduces a new set of complications and adverse events in these patients. Major adverse events with the CF-LVAD include right heart failure, vascular dysfunction, stroke, hepatic failure, and multi-organ failure, complications that may have inflammation as a common etiology. Our aim was to review the current evidence showing a relationship between these adverse events and elevated levels of inflammatory biomarkers in CF-LVAD recipients. PMID:27131263

  7. Effect of culprit-lesion remodeling versus plaque rupture on three-year outcome in patients with acute coronary syndrome.

    PubMed

    Okura, Hiroyuki; Kobayashi, Yoshio; Sumitsuji, Satoru; Terashima, Mitsuyasu; Kataoka, Toru; Masutani, Motomaru; Ohyanagi, Mitsumasa; Shimada, Kenei; Taguchi, Haruyuki; Yasuga, Yuji; Takeda, Yoshihiro; Ohashi, Yoshitaka; Awano, Kojiro; Fujii, Kenichi; Mintz, Gary S

    2009-03-15

    To investigate intravascular ultrasound predictors of long-term clinical outcome in patients with acute coronary syndrome, 94 patients with a first acute coronary syndrome with both preintervention intravascular ultrasound imaging and long-term follow-up were enrolled in this study. Remodeling index was defined as external elastic membrane cross-sectional area at the target lesion divided by that at the proximal reference. Arterial remodeling was defined as either positive (PR: remodeling index >1.05) or intermediate/negative remodeling (remodeling index < or =1.05). Clinical events were death, myocardial infarction, and target-lesion revascularization. Patients were followed up for a mean of 3 years. PR was observed in 50 (53%), and intermediate/negative remodeling, in 44 (47%). During the 3-year follow-up, there were 20 target-lesion revascularization events and 5 deaths (2 cardiac and 3 noncardiac), but no myocardial infarctions. Patients with PR showed significantly lower major adverse cardiac event (MACE; death, myocardial infarction, and target-lesion revascularization)-free survival (log-rank p = 0.03). However, patients with plaque rupture showed a nonsignificant trend toward lower MACE-free survival (p = 0.13), but there were no significant differences in MACE-free survival between those with single versus multiple plaque ruptures. Using multivariate logistic regression analysis, only culprit lesion PR was an independent predictor of MACEs (p = 0.04). In conclusion, culprit-lesion remodeling rather than the presence or absence of culprit-lesion plaque rupture was a strong predictor of long-term (3-year) clinical outcome in patients with acute coronary syndrome. PMID:19268733

  8. The Effects of Chemotherapeutic Agents, Bleomycin, Etoposide, and Cisplatin, on Chromatin Remodeling in Male Rat Germ Cells.

    PubMed

    Bagheri-Sereshki, Negar; Hales, Barbara F; Robaire, Bernard

    2016-04-01

    The coadministration of bleomycin, etoposide, and cisplatin (BEP) has increased the survival rate of testicular cancer patients to over 90%. Previous studies have demonstrated that BEP induces germ cell damage during the final stages of spermatogenesis, when major chromatin remodeling occurs. Chromatin remodeling permits histone-protamine exchange, resulting in sperm head chromatin compaction. This process involves different epigenetic modifications of the core histones. The objective of these studies was to investigate the effects of BEP on epigenetic modifications to histones involved in chromatin remodeling. Brown Norway rats were treated with BEP, and their testes were removed to isolate pachytene spermatocytes and round spermatids by unit gravity sedimentation. Western blot analyses were conducted on extracted proteins to detect the expression of key modified histones. In a second cohort testes were prepared for immunohistochemical analysis. The stage-specific expression of each modified histone mark in rat spermatogenesis suggests the involvement of these modifications in chromatin remodeling. BEP treatment significantly increased expression of H3K9m and decreased that of tH2B (or Hist1h2ba) in pachytene spermatocytes, suggesting that nucleosomes were not destabilized to allow for transcription of genes involved in chromatin remodeling. Moreover, BEP treatment altered the expression of H4K8ac in round and elongating spermatids, suggesting that histone eviction was compromised, leading to a looser chromatin structure in mature spermatozoa. Less-compacted sperm chromatin, with alterations to the sperm epigenome, may have an adverse effect on male fertility. PMID:26911428

  9. Right Ventricular Dysfunction in Chronic Lung Disease

    PubMed Central

    Kolb, Todd M.; Hassoun, Paul M.

    2012-01-01

    Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

  10. Right ventricular dysfunction in children and adolescents conceived by assisted reproductive technologies.

    PubMed

    von Arx, Robert; Allemann, Yves; Sartori, Claudio; Rexhaj, Emrush; Cerny, David; de Marchi, Stefano F; Soria, Rodrigo; Germond, Marc; Scherrer, Urs; Rimoldi, Stefano F

    2015-05-15

    Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity. PMID:25979934

  11. THE IMPACT OF CHEMOTHERAPY AND RADIATION ON THE REMODELING OF ACELLULAR DERMAL MATRICES IN STAGED, PROSTHETIC BREAST RECONSTRUCTION

    PubMed Central

    Myckatyn, Terence M.; Cavallo, Jaime A.; Sharma, Ketan; Gangopadhyay, Noopur; Dudas, Jason R.; Roma, Andres A.; Baalman, Sara; Tenenbaum, Marissa M.; Matthews, Brent D.; Deeken, Corey R.

    2015-01-01

    Background An acellular dermal matrix (ADM) used in prosthetic breast reconstruction will typically incorporate, in time, with the overlying mastectomy skin flap. This remodeling process may be adversely impacted in patients that require chemotherapy and radiation therapies that influence neovascularization and cellular proliferation. Methods Multiple biopsies of the submuscular capsule and ADM were procured from 86 women (N=94 breasts) undergoing exchange of a tissue expander for a breast implant. These were divided by biopsy location : submuscular capsule (control) as well as superiorly, centrally and inferiorly along the ADM. Specimens were assessed grossly for incorporation and semi-quantitatively for cellular infiltration, cell type, fibrous encapsulation, scaffold degradation, extracellular matrix deposition, neovascularization, mean composite remodeling score, as well as Type I and III collagen area and ratio. Five oncologic treatment groups were compared : no adjuvant therapy (untreated), neoadjuvant chemotherapy ± radiation ; and chemotherapy ± radiation. Results ADM and submuscular capsule biopsies were procured 45 to 1805 days after ADM insertion and demonstrated a significant reduction in Type I collagen over time. Chemotherapy adversely impacted fibrous encapsulation relative to the untreated group (p=0.03). Chemotherapy with or without radiation adversely impacted Type I collagen area (p=0.02), cellular infiltration (p<0.01), extracellular matrix deposition (p<0.04), and neovascularization (p<0.01). Radiation exacerbated the adverse impact of chemotherapy for gross incorporation as well as several remodeling parameters. Neoadjuvant chemotherapy also caused a reduction in Type I (p=0.01) and III collagen (p=0.05), extracellular matrix deposition (p=0.03), and scaffold degradation (p=0.02). Conclusions Chemotherapy and radiation therapy limit ADM remodeling. PMID:25539350

  12. Optimized multisite ventricular pacing in postoperative single-ventricle patients.

    PubMed

    Havalad, Vinod; Cabreriza, Santos E; Cheung, Eva W; Aponte-Patel, Linda; Wang, Alice; Cheng, Bin; Wang, Daniel Y; Silver, Eric; Bacha, Emile A; Spotnitz, Henry M

    2014-10-01

    Ventricular dyssynchrony is associated with morbidity and mortality after palliation of a single ventricle. The authors hypothesized that resynchronization with optimized temporary multisite pacing postoperatively would be safe, feasible, and effective. Pacing was assessed in the intensive care unit within the first 24 h after surgery. Two unipolar atrial pacing leads and four bipolar ventricular pacing leads were placed at standardized sites intraoperatively. Pacing was optimized to maximize mean arterial pressure. The protocol tested 11 combinations of the 4 different ventricular lead sites, 6 atrioventricular delays (50-150 ms), and 14 intraventricular delays. Optimal pacing settings were thus determined and ultimately compared in four configurations: bipolar, unipolar, single-site atrioventricular pacing, and intrinsic rhythm. Each patient was his or her own control, and all pacing comparisons were implemented in random sequence. Single-ventricle palliation was performed for 17 children ages 0-21 years. Pacing increased mean arterial pressure (MAP) versus intrinsic rhythm, with the following configurations: bipolar multisite pacing increased MAP by 2.2 % (67.7 ± 2.4 to 69.2 ± 2.4 mmHg; p = 0.013) and unipolar multisite pacing increased MAP by 2.8 % (67.7 ± 2.4 to 69.6 ± 2.7 mmHg; p = 0.002). Atrioventricular single-site pacing increased MAP by 2.1 % (67.7 ± 2.4 to 69.1 ± 2.5 mmHg: p = 0.02, insignificant difference under Bonferroni correction). The echocardiographic fractional area change in nine patients increased significantly only with unipolar pacing (32 ± 3.1 to 36 ± 4.2 %; p = 0.02). No study-related adverse events occurred. Multisite pacing optimization is safe and feasible in the early postoperative period after single-ventricle palliation, with improvements in mean arterial pressure and fractional area shortening. Further study to evaluate clinical benefits is required. PMID:24827078

  13. Adverse possession of subsurface minerals

    SciTech Connect

    Bowles, P.N.

    1983-01-01

    Concepts applicable to adverse possession of subsurface minerals are generally the same as those that apply to adverse possession of all real estate. However, special requirements must be satisfied in order to perfect title to subsurface minerals by adverse possession, particularly when there has been a severance of the true title between surface and subsurface minerals. In those jurisdictions where senior and junior grants came from the state or commonwealth covering the same or some of the same land and in those areas where descriptions of land were vague or not carefully drawn, adverse possession serves to solidify land and mineral ownership. There may be some public, social, and economic justification in rewarding, with good title, those who take possession and use real estate for its intended use, including the extraction of subsurface minerals. 96 refernces.

  14. Aortic Stenosis, a Left Ventricular Disease: Insights from Advanced Imaging.

    PubMed

    Badiani, Sveeta; van Zalen, Jet; Treibel, Thomas A; Bhattacharyya, Sanjeev; Moon, James C; Lloyd, Guy

    2016-08-01

    Aortic stenosis (AS) is the most common primary valve disorder in the elderly with an increasing prevalence. It is increasingly clear that it is also a disease of the left ventricle (LV) rather than purely the aortic valve. The transition from left ventricular hypertrophy to fibrosis results in the eventual adverse effects on systolic and diastolic function. Appropriate selection of patients for aortic valve intervention is crucial, and current guidelines recommend aortic valve replacement in severe AS with symptoms or in asymptomatic patients with left ventricular ejection fraction (LVEF) <50 %. LVEF is not a sensitive marker and there are other parameters used in multimodality imaging techniques, including longitudinal strain, exercise stress echo and cardiac MRI that may assist in detecting subclinical and subtle LV dysfunction. These findings offer potentially better ways to evaluate patients, time surgery, predict recovery and potentially offer targets for specific therapies. This article outlines the pathophysiology behind the LV response to aortic stenosis and the role of advanced multimodality imaging in describing it. PMID:27384950

  15. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  16. Low cardiac output due to acute right ventricular dysfunction and cardiopulmonary interactions in congenital heart disease (2013 Grover Conference series)

    PubMed Central

    2014-01-01

    Abstract The importance of right ventricular dysfunction, as a driver of symptoms and outcomes in the normal biventricular circulation, is increasingly recognized. However, the pathophysiologic mechanisms underlying the role of the right ventricle in acute and chronic hemodynamic deterioration are less well understood. This review aims to clarify the impact of acute right ventricular dysfunction on biventricular interactions and, in turn, to discuss the role of cardiopulmonary interactions in the normal circulation and when modified by the presence of associated structural malformations. Such interactions may be adverse or beneficial, and a more complete understanding of their importance may result in novel therapeutic strategies and improved outcomes. PMID:25006438

  17. Homocysteine enriched diet leads to prolonged QT interval and reduced left ventricular performance in telemetric monitored mice

    PubMed Central

    Rosenberger, D; Gargoum, R; Tyagi, N; Metreveli, N; Sen, U; Maldonado, C; Tyagi, S

    2009-01-01

    Background and Aims Homocysteine (Hcy) is a sulfur-containing, non-protein amino acid produced in the metabolic pathway of methionine. Hyperhomocysteinemia is associated with cerebro- and cardiovascular disease in industrialized countries mostly resulting from protein rich diet and sedentary life style. Matrix metalloproteinases are involved in cardiac remodeling, leading to degradation of intercellular junctions, cardiac connexins and basement membranes. The study was designed to investigate the relationship between Hcy, cardiac remodeling, cardiac performance, and rhythm disturbances in an animal model of hyperhomocysteinemia. We tested the hypothesis that induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 leads to connexin 40, connexin 43, connexin 45 expression changes contributing to decreased cardiac performance and disturbed atrioventricular conduction. Methods and Results Hcy was added to drinking water of male C57/BL6J mice to achieve moderate Hcy blood levels. ECG was monitored in conscious mice with a telemetric ECG device; echocardiography was used for assessment of left ventricular function. Immunoblotting was used to evaluate matrix metalloproteinase-2, matrix metalloproteinase-9, connexin 40, connexin 43, and connexin 45 expression in cardiac tissue. Animals fed Hcy showed significant prolongation of QRS, QTc, and PR intervals along with reduced left ventricular function. Western blotting showed increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and decreased expression of connexin 40, 43, and 45. Conclusion Hcy has been identified as a nutritional factor contributing to cardiovascular disease. Cardiac remodelling induced by matrix metalloproteinase-2 and matrix metalloproteinase-9 and decreased expression of connexin 40, 43, and 45 appears to play a role in the pathomechansim of atrioventricular conduction delay and ventricular dilatation in hyperhomocysteinemia. PMID:20227264

  18. Coronary haemodynamics in left ventricular hypertrophy.

    PubMed Central

    Wallbridge, D. R.; Cobbe, S. M.

    1996-01-01

    BACKGROUND: Left ventricular hypertrophy is associated with an increased risk of cardiovascular morbidity and mortality. Previous studies have shown that patients with left ventricular hypertrophy develop electrocardiographic changes and left ventricular dysfunction during acute hypotension, and suggest that the lower end of autoregulation may be shifted upwards. AIM: To measure coronary blood flow (velocity) and flow reserve during acute hypotension in patients with left ventricular hypertrophy. PATIENTS: Eight patients with atypical chest pain and seven with hypertensive left ventricular hypertrophy; all with angiographically normal epicardial vessels. SETTING: Tertiary referral centre. METHODS: The physiological range of blood pressure was determined by previous ambulatory monitoring. Left ventricular mass was determined by echocardiography. At cardiac catheterisation, left coronary blood flow velocity was measured using a Judkins style Doppler tipped catheter. During acute hypotension with sodium nitroprusside, coronary blood flow velocity was recorded at rest and during maximal hyperaemia induced by intracoronary injection of adenosine. Quantitative coronary angiography was performed manually. RESULTS: For both groups coronary blood flow velocity remained relatively constant over a range of physiological diastolic blood pressures and showed a steep relation with diastolic blood pressure during maximal hyperaemia with intracoronary adenosine. Absolute coronary blood flow (calculated from quantitative angiographic data), standardised for left ventricular mass, showed reduced flow in the hypertensive group at rest and during maximal vasodilatation. CONCLUSION: The results are consistent with an inadequate blood supply to the hypertrophied heart, but no upward shift of the lower end of the autoregulatory range was observed. PMID:8705764

  19. Transdifferentiation of endothelial cells to smooth muscle cells play an important role in vascular remodelling.

    PubMed

    Coll-Bonfill, Núria; Musri, Melina Mara; Ivo, Victor; Barberà, Joan Albert; Tura-Ceide, Olga

    2015-01-01

    Pulmonary artery remodelling it is a major feature of pulmonary hypertension (PH). It is characterised by cellular and structural changes of the pulmonary arteries causing higher pulmonar vascular resistance and right ventricular failure. Abnormal deposition of smooth muscle-like (SM-like) cells in normally non-muscular, small diameter vessels and a deregulated control of endothelial cells are considered pathological features of PH. The origin of the SM-like cells and the mechanisms underlying the development and progression of this remodelling process are not understood. Endothelial cells within the intima may migrate from their organised layer of cells and transition to mesenchymal or SM-like phenotype in a process called endothelial-mesenchymal transition (EnMT). Traditionally, Waddington's epigenetic landscape illustrates that fates of somatic cells are progressively determined to compulsorily follow a downhill differentiation pathway. EnMT induces the transformation of cells with stem cell traits, therefore contrasting Waddington's theory and confirming that cell fate seems to be far more flexible than previously thought. The prospect of therapeutic inhibition of EnMT to delay or prevent PH may represent a promising new treatment modality. PMID:25973327

  20. TLR4 regulates pulmonary vascular homeostasis and remodeling via redox signaling

    PubMed Central

    Ma, Liping; Ambalavanan, Namasivayam; Liu, Hui; Sun, Yong; Jhala, Nirag; Bradley, Wayne E.; Dell’Italia, Louis J.; Michalek, Sue; Wu, Hui; Steele, Chad; Benza, Raymond L; Chen, Yabing

    2016-01-01

    Pulmonary arterial hypertension (PAH) contributes to morbidity and mortality of patients with lung and heart diseases. We demonstrated that hypoxia induced PAH and increased pulmonary arterial wall thickness in wild-type mice. Mice deficient in toll-like receptor 4 (TLR4−/−) spontaneously developed PAH, which was not further enhanced by hypoxia. Echocardiography determined right ventricular hypertrophy and decreased pulmonary arterial acceleration time were associated with the development of PAH in TLR4−/− mice. In pulmonary arterial smooth muscle cells (PASMC), hypoxia decreased TLR4 expression and induced reactive oxygen species (ROS) and Nox1/Nox4. Inhibition of NADPH oxidase decreased hypoxia-induced proliferation of wild-type PASMC. PASMC derived from TLR4−/− mice exhibited increased ROS and Nox4/Nox1 expression. Our studies demonstrate an important role of TLR4 in maintaining normal pulmonary vasculature and in hypoxia-induced PAH. Inhibition of TLR4, by genetic ablation or hypoxia, increases the expression of Nox1/Nox4 and induces PASMC proliferation and vascular remodeling. These results support a novel function of TLR4 in regulating the development of PAH and reveal a new regulatory axis contributing to TLR4 deficiency-induced vascular hypertrophy and remodeling. PMID:26709781

  1. Analyzing Remodeling of Cardiac Tissue: A Comprehensive Approach Based on Confocal Microscopy and 3D Reconstructions.

    PubMed

    Seidel, Thomas; Edelmann, J-C; Sachse, Frank B

    2016-05-01

    Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 µm. This allowed extensive analyzes revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control vs. infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale. PMID:26399990

  2. A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance

    PubMed Central

    Helfer, Gisela; Ross, Alexander W.; Thomson, Lynn M.; Mayer, Claus D.; Stoney, Patrick N.; McCaffery, Peter J.; Morgan, Peter J.

    2016-01-01

    Long-term and reversible changes in body weight are typical of seasonal animals. Thyroid hormone (TH) and retinoic acid (RA) within the tanycytes and ependymal cells of the hypothalamus have been implicated in the photoperiodic response. We investigated signalling downstream of RA and how this links to the control of body weight and food intake in photoperiodic F344 rats. Chemerin, an inflammatory chemokine, with a known role in energy metabolism, was identified as a target of RA. Gene expression of chemerin (Rarres2) and its receptors were localised within the tanycytes and ependymal cells, with higher expression under long (LD) versus short (SD) photoperiod, pointing to a physiological role. The SD to LD transition (increased food intake) was mimicked by 2 weeks of ICV infusion of chemerin into rats. Chemerin also increased expression of the cytoskeletal protein vimentin, implicating hypothalamic remodelling in this response. By contrast, acute ICV bolus injection of chemerin on a 12 h:12 h photoperiod inhibited food intake and decreased body weight with associated changes in hypothalamic neuropeptides involved in growth and feeding after 24 hr. We describe the hypothalamic ventricular zone as a key site of neuroendocrine regulation, where the inflammatory signal, chemerin, links TH and RA signaling to hypothalamic remodeling. PMID:27225311

  3. Ventricular Aneurysm Following Myocardial Infarction

    PubMed Central

    Walters, M. B.

    1966-01-01

    Cineradiographic examination appears to be the best method for the study of cardiac pulsations. Fifty consecutive patients, who had sustained transmural myocardial infarction at least six months previously, were studied by this technique. Thirty-six had some abnormality of pulsation and eight had dynamic ventricular aneurysm. Six of the eight had suffered severe infarct. Functional recovery in those with aneurysm was not as complete as in the rest of the group. Two made a poor functional recovery, two a fair recovery, and four a moderately good recovery. Clinically, there were no systemic emboli in the patients with dynamic aneurysms. Five of the 50 had persistent ST-segment elevation and “coving” of the T waves; three of these patients had aneurysms. There was no good correlation between the electrocardiographic site of the infarct and the site of the abnormal pulsation. ImagesFig. 1 PMID:5928534

  4. Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche.

    PubMed Central

    Kuo, Chay T.; Mirzadeh, Zaman; Soriano-Navarro, Mario; Rašin, Mladen; Wang, Denan; Shen, Jie; Šestan, Nenad; Garcia-Verdugo, Jose; Alvarez-Buylla, Arturo; Jan, Lily Y.; Jan, Yuh-Nung

    2007-01-01

    SUMMARY Neural stem cells are retained in the postnatal subventricular zone (SVZ), a specialized neurogenic niche with unique cytoarchitecture and cell-cell contacts. Although the SVZ stem cells continuously regenerate, how they and the niche respond to local changes is unclear. Here we generated nestin-creERtm transgenic mice with inducible Cre recombinase in the SVZ, and removed Numb/Numblike, key regulators of embryonic neurogenesis from postnatal SVZ progenitors and ependymal cells. This resulted in severe damage to brain lateral ventricle integrity, and identified previously unknown roles for Numb/Numblike in regulating ependymal wall integrity and SVZ neuroblast survival. Surprisingly, the ventricular damage was eventually repaired: SVZ reconstitution and ventricular wall remodeling were mediated by progenitors that escaped Numb deletion. Our results show a self-repair mechanism in the mammalian brain, and may have implications for niche plasticity in other areas of stem cell biology, and for the therapeutic use of neural stem cells in neurodegenerative diseases. PMID:17174898

  5. Green tea attenuates cardiovascular remodelling and metabolic symptoms in high carbohydrate-fed rats.

    PubMed

    Rickman, Celestine; Iyer, Abishek; Chan, Vincent; Brown, Lindsay

    2010-12-01

    Excess carbohydrate in the diet may initiate a chronic state of oxidative stress exacerbating the clinical and biochemical symptoms of diet-induced type 2 diabetes, especially glucose intolerance, lipid abnormalities and cardiovascular complications. This study has tested whether green tea, rich in antioxidants, improves both cardiovascular symptoms and glucose intolerance and also reduces oxidative stress in rats fed a high carbohydrate diet. Male 8 week old Wistar rats were fed a diet including fructose and condensed milk (each 40%) for 16 weeks (112 days); control rats were fed corn starch. Green tea-containing food was started from day 1 for the prevention protocol and from day 56 for the reversal protocol. High carbohydrate diet-fed rats showed glucose intolerance, hypertension, mild left ventricular hypertrophy, approximate doubling of cardiac interstitial and perivascular collagen deposition, increased passive diastolic stiffness and increased plasma malondialdehyde concentrations. Administration of green tea to high carbohydrate diet-fed rats prevented and reversed glucose intolerance and the increased systolic blood pressure, left ventricular wet weight, interstitial collagen and passive diastolic stiffness. Plasma malondialdehyde concentrations were also normalized. In summary, treatment with green tea both prevented and reversed the cardiovascular remodelling and metabolic changes seen in high carbohydrate-fed rats suggesting a chronic state of oxidative stress plays a key role in the symptom initiation and progression. Further, green tea may be a useful complementary therapy in diet-induced type 2 diabetes. PMID:20874683

  6. Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling

    PubMed Central

    Paradis, Pierre; Dali-Youcef, Nassim; Paradis, François W.; Thibault, Gaétan; Nemer, Mona

    2000-01-01

    Angiotensin II (AII) is a major determinant of arterial pressure and volume homeostasis, mainly because of its vascular action via the AII type 1 receptor (AT1R). AII has also been implicated in the development of cardiac hypertrophy because angiotensin I-converting enzyme inhibitors and AT1R antagonists prevent or regress ventricular hypertrophy in animal models and in human. However, because these treatments impede the action of AII at cardiac as well as vascular levels, and reduce blood pressure, it has been difficult to determine whether AII action on the heart is direct or a consequence of pressure-overload. To determine whether AII can induce cardiac hypertrophy directly via myocardial AT1R in the absence of vascular changes, transgenic mice overexpressing the human AT1R under the control of the mouse α-myosin heavy chain promoter were generated. Cardiomyocyte-specific overexpression of AT1R induced, in basal conditions, morphologic changes of myocytes and nonmyocytes that mimic those observed during the development of cardiac hypertrophy in human and in other mammals. These mice displayed significant cardiac hypertrophy and remodeling with increased expression of ventricular atrial natriuretic factor and interstitial collagen deposition and died prematurely of heart failure. Neither the systolic blood pressure nor the heart rate were changed. The data demonstrate a direct myocardial role for AII in the development of cardiac hypertrophy and failure and provide a useful model to elucidate the mechanisms of action of AII in the pathogenesis of cardiac diseases. PMID:10639182

  7. Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling.

    PubMed

    Paradis, P; Dali-Youcef, N; Paradis, F W; Thibault, G; Nemer, M

    2000-01-18

    Angiotensin II (AII) is a major determinant of arterial pressure and volume homeostasis, mainly because of its vascular action via the AII type 1 receptor (AT1R). AII has also been implicated in the development of cardiac hypertrophy because angiotensin I-converting enzyme inhibitors and AT1R antagonists prevent or regress ventricular hypertrophy in animal models and in human. However, because these treatments impede the action of AII at cardiac as well as vascular levels, and reduce blood pressure, it has been difficult to determine whether AII action on the heart is direct or a consequence of pressure-overload. To determine whether AII can induce cardiac hypertrophy directly via myocardial AT1R in the absence of vascular changes, transgenic mice overexpressing the human AT1R under the control of the mouse alpha-myosin heavy chain promoter were generated. Cardiomyocyte-specific overexpression of AT1R induced, in basal conditions, morphologic changes of myocytes and nonmyocytes that mimic those observed during the development of cardiac hypertrophy in human and in other mammals. These mice displayed significant cardiac hypertrophy and remodeling with increased expression of ventricular atrial natriuretic factor and interstitial collagen deposition and died prematurely of heart failure. Neither the systolic blood pressure nor the heart rate were changed. The data demonstrate a direct myocardial role for AII in the development of cardiac hypertrophy and failure and provide a useful model to elucidate the mechanisms of action of AII in the pathogenesis of cardiac diseases. PMID:10639182

  8. Cardiac fibrosis in myocardial infarction-from repair and remodeling to regeneration.

    PubMed

    Talman, Virpi; Ruskoaho, Heikki

    2016-09-01

    Ischemic cell death during a myocardial infarction leads to a multiphase reparative response in which the damaged tissue is replaced with a fibrotic scar produced by fibroblasts and myofibroblasts. This also induces geometrical, biomechanical, and biochemical changes in the uninjured ventricular wall eliciting a reactive remodeling process that includes interstitial and perivascular fibrosis. Although the initial reparative fibrosis is crucial for preventing rupture of the ventricular wall, an exaggerated fibrotic response and reactive fibrosis outside the injured area are detrimental as they lead to progressive impairment of cardiac function and eventually to heart failure. In this review, we summarize current knowledge of the mechanisms of both reparative and reactive cardiac fibrosis in response to myocardial infarction, discuss the potential of inducing cardiac regeneration through direct reprogramming of fibroblasts and myofibroblasts into cardiomyocytes, and review the currently available and potential future therapeutic strategies to inhibit cardiac fibrosis. Graphical abstract Reparative response following a myocardial infarction. Hypoxia-induced cardiomyocyte death leads to the activation of myofibroblasts and a reparative fibrotic response in the injured area. Right top In adult mammals, the fibrotic scar formed at the infarcted area is permanent and promotes reactive fibrosis in the uninjured myocardium. Right bottom In teleost fish and newts and in embryonic and neonatal mammals, the initial formation of a fibrotic scar is followed by regeneration of the cardiac muscle tissue. Induction of post-infarction cardiac regeneration in adult mammals is currently the target of intensive research and drug discovery attempts. PMID:27324127

  9. Ventricular capture by anodal pacemaker stimulation.

    PubMed

    Occhetta, Eraldo; Bortnik, Miriam; Marino, Paolo

    2006-05-01

    This report describes the case of an 86-year-old male with syncopal paroxysmal 2:1 atrioventricular block and a single chamber VVI pacemaker programmed to bipolar sensing and unipolar pacing. After recurrence of syncope, a complete loss of ventricular capture with regular ventricular sensing was observed on ECG; fluoroscopic examination suggested perforation of the right ventricle by the helix of the implanted screw-in lead. Reprogramming the pacemaker to bipolar pacing/sensing resulted in regular ventricular capture and sensing, suggesting effective anodal stimulation from the ring electrode permitting complete non-invasive palliation. PMID:16636000

  10. Ventricular-Vascular Interaction in Heart Failure

    PubMed Central

    Borlaug, Barry A.; Kass, David A.

    2008-01-01

    Synopsis Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF). HFpEF patients tend to be older, female, and hypertensive, and characteristically display increased ventricular and arterial stiffening. In this review, we discuss the pathophysiology of abnormal ventriculoarterial stiffening and how the latter affects ventricular function, cardiovascular hemodynamics, reserve capacity, and symptoms. We conclude by exploring how novel treatment strategies targeting abnormal ventricular-arterial interaction might prove useful in the treatment of patients with HFpEF. PMID:18313622

  11. Memory and ventricular size in alcoholics.

    PubMed

    Acker, C; Jacobson, R R; Lishman, W A

    1987-05-01

    The relationship between memory performance and CT scan measures of ventricular size was investigated in a sample of 39 chronic alcoholics and 39 controls. Measures of verbal, non-verbal, recognition and recall memory were derived from the tests administered and were viewed in relation to the lateral ventricle and third ventricular size measurements. The results showed that the memory performance of male alcoholics was significantly related to measures of third ventricular size, but probably not to measures of the lateral ventricles. An association between verbal memory performance and CT scan measures was found in the male controls. PMID:3602226

  12. Functional annulus remodelling using a prosthetic ring in tricuspid aortic valve repair: mid-term results†

    PubMed Central

    Fattouch, Khalil; Castrovinci, Sebastiano; Murana, Giacomo; Nasso, Giuseppe; Guccione, Francesco; Dioguardi, Pietro; Salardino, Massimo; Bianco, Giuseppe; Speziale, Giuseppe

    2014-01-01

    OBJECTIVES The functional aortic valve annulus (FAVA) is a complex unit with proximal (aorto-ventricular junction) and distal (sinotubular junction) components. The aim of our study was to evaluate the impact of the total FAVA remodelling, using a prosthetic ring, on mid-term clinical and echocardiographic results after aortic valve repair. METHODS Since February 2003, 250 patients with tricuspid aortic valve insufficiency (AI) underwent aortic valve repair. FAVA dilatation was treated by prosthetic ring in 52 patients, by isolated subcommissural plasty in 62, by subcommissural plasty plus ascending aortic replacement in 57 and by David's reimplantation procedure in 79. Survival rate and freedom from recurrent AI greater than or equal to moderate were evaluated by Kaplan–Meier. RESULTS Overall late survival was 90.4%. Late cardiac-related deaths occurred in 15 patients. At follow-up, 36 (16%) patients had recurrent AI greater than or equal to moderate because of cusp reprolapse and/or FAVA redilatation. Freedom from recurrent AI was significantly higher for patients who underwent David's procedure or FAVA remodelling by prosthetic ring than those who underwent isolated subcommissural plasty (P < 0.01) or subcommissural plasty plus ascending aortic replacement (P = 0.02). There was no statistical difference between David's procedure and prosthetic ring annuloplasty (P = 0.26). CONCLUSION FAVA remodelling using a prosthetic ring is a safe procedure in aortic valve repair surgery thanks to long-term annulus stabilization and it is a pliable alternative to David's procedure in selected patients. This technique may be used in all patients with slight root dilatation to avoid aggressive root reimplantation. We also recommended total FAVA annuloplasty in all patients who underwent aortic valve repair to improve long-term repair results. PMID:24065345

  13. Asiatic acid alleviates cardiovascular remodelling in rats with L-NAME-induced hypertension.

    PubMed

    Bunbupha, Sarawoot; Prachaney, Parichat; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Welbat, Jariya Umka; Pakdeechote, Poungrat

    2015-11-01

    A previous study demonstrated the antihypertensive effect of asiatic acid. The current study investigates the effect of asiatic acid on cardiovascular remodelling and possible mechanisms involved in Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg per day) for 3 weeks in order to induce hypertension. Hypertensive rats were administered asiatic acid (20 mg/kg per day) or vehicle for a further 2 weeks. It was found that hypertensive rats showed high systolic blood pressure, left ventricular (LV) hypertrophy, increases in LV fibrosis, aortic wall thickness and aortic collagen deposition (P < 0.05). Moreover, decreased plasma nitrate and nitrite (NOx) and increased plasma tumor necrosis factor alpha (TNF-α) were observed in hypertensive rats (P < 0.05). This was consistent with downregulation of endothelial nitric oxide synthase (eNOS) expression and upregulation of inducible nitric oxide synthase (iNOS) expression in heart and aortic tissues (P < 0.05). Levels of malondialdehyde (MDA) in plasma, aortic and heart tissues were significantly increased in hypertensive rats (P < 0.05). Asiatic acid markedly reduced blood pressure, alleviated cardiovascular remodelling, and restored plasma NOx and TNF-α as well as eNOS/iNOS expression in heart and aortic tissues (P < 0.05). Additionally, there was a significant reduction of MDA levels in the tissues of treated hypertensive rats. In conclusion, this study demonstrates the therapeutic effects of asiatic acid on blood pressure and cardiovascular remodelling, which is possibly related to the restoration of eNOS/iNOS expression, and the resulting anti-inflammatory and antioxidant activities. PMID:26234646

  14. TRPV1 gene deletion exacerbates inflammation and atypical cardiac remodeling after myocardial infarction

    PubMed Central

    Huang, Wei; Rubinstein, Jack; Prieto, Alejandro R.; Thang, Loc Vinh; Wang, Donna H.

    2009-01-01

    The transient receptor potential vanilloid (TRPV1) channels expressed in sensory afferent fibers innervating the heart may be activated by proton or endovanilloids released during myocardial ischemia (MI), leading to angina. Although our previous in vitro data indicate that TRPV1 activation may preserve cardiac function after ischemia-reperfusion (I/R) injury, the underlying mechanisms are largely unknown. To test the hypothesis that TRPV1 modulates inflammatory and early remodeling processes to prevent cardiac functional deterioration after myocardial infarction, TRPV1-null mutant (TRPV1-/-) and wild-type (WT) mice were subjected to left anterior descending coronary ligation or sham operation. The infarct size was greater in TRPV1-/- than in WT mice (P < 0.001) 3 days after MI, and the mortality rate was higher in TRPV1-/- than in WT mice (P < 0.05) 7 days after MI. The levels of plasma cardiac troponin I; cytokines including TNF-α, IL-1β, and IL-6; chemokines including MCP-1 and MIP-2; infiltration of inflammatory cells including neutrophil, macrophage, and myofibroblast; as well as collagen contents were greater in TRPV1-/- than in WT mice (P < 0.05) in the infarct area on day 3 and 7 after MI. Changes in left ventricular (LV) geometry led to increased end-systolic and -diastolic diameters and reduced contractile function in TRPV1-/- compared to WT mice. These data show that TRPV1 gene deletion results in excessive inflammation, disproportional LV remodeling, and deteriorated cardiac function after MI, indicating that TRPV1 may prevent infarct expansion and cardiac injury by inhibiting inflammation and abnormal tissue remodeling. PMID:19114647

  15. Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats

    PubMed Central

    Junqueira, Adriana; Cicogna, Antônio Carlos; Engel, Letícia Estevam; Aldá, Maiara Almeida; de Tomasi, Loreta Casquel; Giuffrida, Rogério; Giometti, Inês Cristina; Freire, Ana Paula Coelho Figueira; Aguiar, Andreo Fernando; Pacagnelli, Francis Lopes

    2016-01-01

    Background Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. Objective To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Methods Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). Results There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). Conclusion GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport. PMID:26647722

  16. Inhibition of Histone Deacetylases Preserves Myocardial Performance and Prevents Cardiac Remodeling through Stimulation of Endogenous Angiomyogenesis

    PubMed Central

    Zhang, Ling; Qin, Xin; Zhao, Yu; Fast, Loren; Zhuang, Shougang; Liu, Paul; Cheng, Guangmao

    2012-01-01

    We have previously shown that the inhibition of histone deacetylases (HDACs) protects the heart against acute myocardial ischemia and reperfusion injury. We also demonstrated that HDAC inhibition stimulates myogenesis and angiogenesis in a cultured embryonic stem cell model. We investigate whether in vivo inhibition of HDAC preserves cardiac performance and prevents cardiac remodeling in mouse myocardial infarction (MI) through the stimulation of endogenous regeneration. MI was created by ligation of the left descending artery. Animals were divided into three groups: 1) sham group, animals that underwent thoracotomy without MI; 2) MI, animals that underwent MI; and 3) MI + trichostatin A (TSA), MI animals that received a daily intraperitoneal injection of TSA. In addition, infarcted mice received a daily intraperitoneal injection of TSA (0.1 mg/kg), a selective HDAC inhibitor. 5-Bromo-2-deoxyuridine (50 mg/kg) was delivered every other day to pulse-chase label in vivo endogenous cardiac replication. Eight weeks later, the MI hearts showed a reduction in ventricular contractility. HDAC inhibition increased the improvement of myocardial functional recovery after MI, which was associated with the prevention of myocardial remodeling and reduction of myocardial and serum tumor necrosis factor α. HDAC inhibition enhanced the formation of new myocytes and microvessels, which was consistent with the robust increase in proliferation and cytokinesis in the MI hearts. An increase in angiogenic response was demonstrated in MI hearts receiving TSA treatment. It is noteworthy that TSA treatment significantly inhibited HDAC activity and increased phosphorylation of Akt-1, but decreased active caspase 3. Taken together, our results indicate that HDAC inhibition preserves cardiac performance and mitigates myocardial remodeling through stimulating cardiac endogenous regeneration. PMID:22271820

  17. Intravenous disopyramide phosphate and ventricular overdrive pacing in the termination of paroxysmal ventricular tachycardia.

    PubMed

    Camm, J; Ward, D; Washington, H G; Spurrell, R A

    1979-07-01

    Both antiarrhythmic drugs and bursts of rapid ventricular pacing provide alternatives to DC cardioversion for the treatment of paroxysmal ventricular tachycardia. This report considers the individual and combined success of burst ventricular pacing and intravenous disopyramide phosphate in the tretment of 11 examples of paroxysmal ventricular tachycardia. Rapid ventricular pacing, at a rate of up to 50 beats/min faster than the tachycardia rate terminated 7 of the tachycardias. Intravenous disopyramide resulted in increased tachycardiac cycle length (342 +/- 34 ms-385 +/- 56 ms), increased QRS complex width (147 +/- 42 ms-180 +/- 41 ms) and termination of 8 the tachycardias. The remaining 3 tachycardias could be terminated by bursts of ventricular pacing following the infusion of disopyramide. Of these, 2 could not be terminated prior to disopyramide. The use of both techniques allowed the extinction of all 11 tachycardias and prevented the need to proceed to DC conversion. PMID:95308

  18. Remodeling of Calcium Entry Pathways in Cancer.

    PubMed

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2016-01-01

    Ca(2+) entry pathways play important roles in control of many cellular functions, including long-term proliferation, migration and cell death. In recent years, it is becoming increasingly clear that, in some types of tumors, remodeling of Ca(2+) entry pathways could contribute to cancer hallmarks such as excessive proliferation, cell migration and invasion as well as resistance to cell death or survival. In this chapter we briefly review findings related to remodeling of Ca(2+) entry pathways in cancer with emphasis on the mechanisms that contribute to increased store-operated Ca(2+) entry (SOCE) and store-operated currents (SOCs) in colorectal cancer cells. Finally, since SOCE appears critically involved in colon tumorogenesis, the inhibition of SOCE by aspirin and other NSAIDs and its possible contribution to colon cancer chemoprevention is reviewed. PMID:27161240

  19. Chromatin Remodeling, DNA Damage Repair and Aging

    PubMed Central

    Liu, Baohua; Yip, Raymond KH; Zhou, Zhongjun

    2012-01-01

    Cells are constantly exposed to a variety of environmental and endogenous conditions causing DNA damage, which is detected and repaired by conserved DNA repair pathways to maintain genomic integrity. Chromatin remodeling is critical in this process, as the organization of eukaryotic DNA into compact chromatin presents a natural barrier to all DNA-related events. Studies on human premature aging syndromes together with normal aging have suggested that accumulated damages might lead to exhaustion of resources that are required for physiological functions and thus accelerate aging. In this manuscript, combining the present understandings and latest findings, we focus mainly on discussing the role of chromatin remodeling in the repair of DNA double-strand breaks (DSBs) and regulation of aging. PMID:23633913

  20. REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING

    PubMed Central

    Aggarwal, Saurabh; Gross, Christine M.; Sharma, Shruti; Fineman, Jeffrey R.; Black, Stephen M.

    2014-01-01

    The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell (SMC) hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the anti-oxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphate-oxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting co-factor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension. PMID:23897679

  1. Perspectives on biological growth and remodeling

    PubMed Central

    Ambrosi, D.; Ateshian, G. A.; Arruda, E. M.; Cowin, S. C.; Dumais, J.; Goriely, A.; Holzapfel, G. A.; Humphrey, J. D.; Kemkemer, R.; Kuhl, E.; Olberding, J. E.; Taber, L. A.; Garikipati, K.

    2011-01-01

    The continuum mechanical treatment of biological growth and remodeling has attracted considerable attention over the past fifteen years. Many aspects of these problems are now well-understood, yet there remain areas in need of significant development from the standpoint of experiments, theory, and computation. In this perspective paper we review the state of the field and highlight open questions, challenges, and avenues for further development. PMID:21532929

  2. Polymorphic Ventricular Tachycardia/Ventricular Fibrillation and Sudden Cardiac Death in the Normal Heart.

    PubMed

    Shah, Ashok J; Hocini, Meleze; Denis, Arnaud; Derval, Nicolas; Sacher, Frederic; Jais, Pierre; Haissaguerre, Michel

    2016-09-01

    Primary electrical diseases manifest with polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) and along with idiopathic VF contribute to about 10% of sudden cardiac deaths (SCDs) overall. These disorders include long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, and early repolarization syndrome. This article reviews the clinical electrophysiological management of PMVT/VF in a structurally normal heart affected with these disorders. PMID:27521091

  3. Link between vitamin D and airway remodeling

    PubMed Central

    Berraies, Anissa; Hamzaoui, Kamel; Hamzaoui, Agnes

    2014-01-01

    In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma. PMID:24729717

  4. Tissue Remodelling following Resection of Porcine Liver

    PubMed Central

    Nygård, Ingvild Engdal; Mortensen, Kim Erlend; Hedegaard, Jakob; Conley, Lene Nagstrup; Bendixen, Christian; Sveinbjørnsson, Baldur; Revhaug, Arthur

    2015-01-01

    Aim. To study genes regulating the extracellular matrix (ECM) and investigate the tissue remodelling following liver resection in porcine. Methods. Four pigs with 60% partial hepatectomy- (PHx-) induced liver regeneration were studied over six weeks. Four pigs underwent sham surgery and another four pigs were used as controls of the normal liver growth. Liver biopsies were taken upon laparotomy, after three and six weeks. Gene expression profiles were obtained using porcine-specific oligonucleotide microarrays. Immunohistochemical staining was performed and a proliferative index was assessed. Results. More differentially expressed genes were associated with the regulation of ECM in the resection group compared to the sham and control groups. Secreted protein acidic and rich in cysteine (SPARC) and collagen 1, alpha 2 (COL1A2) were both upregulated in the early phase of liver regeneration, validated by immunopositive cells during the remodelling phase of liver regeneration. A broadened connective tissue was demonstrated by Masson's Trichrome staining, and an immunohistochemical staining against pan-Cytokeratin (pan-CK) demonstrated a distinct pattern of migrating cells, followed by proliferating cell nuclear antigen (PCNA) positive nuclei. Conclusions. The present study demonstrates both a distinct pattern of PCNA positive nuclei and a deposition of ECM proteins in the remodelling phase of liver regeneration. PMID:26240819

  5. Stepwise nucleosome translocation by RSC remodeling complexes.

    PubMed

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-01-01

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1-2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome. PMID:26895087

  6. Stepwise nucleosome translocation by RSC remodeling complexes

    PubMed Central

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-01-01

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1–2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome. DOI: http://dx.doi.org/10.7554/eLife.10051.001 PMID:26895087

  7. Angiotensin-(1–7) attenuates angiotensin II-induced cardiac remodeling associated with upregulation of dual-specificity phosphatase 1

    PubMed Central

    McCollum, LaTronya T.; Gallagher, Patricia E.

    2012-01-01

    Chronic hypertension induces cardiac remodeling, including left ventricular hypertrophy and fibrosis, through a combination of both hemodynamic and humoral factors. In previous studies, we showed that the heptapeptide ANG-(1–7) prevented mitogen-stimulated growth of cardiac myocytes in vitro, through a reduction in the activity of the MAPKs ERK1 and ERK2. In this study, saline- or ANG II-infused rats were treated with ANG-(1–7) to determine whether the heptapeptide reduces myocyte hypertrophy in vivo and to identify the signaling pathways involved in the process. ANG II infusion into normotensive rats elevated systolic blood pressure >50 mmHg, in association with increased myocyte cross-sectional area, ventricular atrial natriuretic peptide mRNA, and ventricular brain natriuretric peptide mRNA. Although infusion with ANG-(1–7) had no effect on the ANG II-stimulated elevation in blood pressure, the heptapeptide hormone significantly reduced the ANG II-mediated increase in myocyte cross-sectional area, interstitial fibrosis, and natriuretic peptide mRNAs. ANG II increased phospho-ERK1 and phospho-ERK2, whereas cotreatment with ANG-(1–7) reduced the phosphorylation of both MAPKs. Neither ANG II nor ANG-(1–7) altered the ERK1/2 MAPK kinase MEK1/2. However, ANG-(1–7) infusion, with or without ANG II, increased the MAPK phosphatase dual-specificity phosphatase (DUSP)-1; in contrast, treatment with ANG II had no effect on DUSP-1, suggesting that ANG-(1–7) upregulates DUSP-1 to reduce ANG II-stimulated ERK activation. These results indicate that ANG-(1–7) attenuates cardiac remodeling associated with a chronic elevation in blood pressure and upregulation of a MAPK phosphatase and may be cardioprotective in patients with hypertension. PMID:22140049

  8. MicroRNA and vascular remodelling in acute vascular injury and pulmonary vascular remodelling

    PubMed Central

    McDonald, Robert A.; Hata, Akiko; MacLean, Margaret R.; Morrell, Nicholas W.; Baker, Andrew H.

    2012-01-01

    Vascular remodelling is an integral pathological process central to a number of cardiovascular diseases. The complex interplay between distinct cell populations in the vessel wall following vascular injury leads to inflammation, cellular dysfunction, pro-growth signals in the smooth muscle cell (SMC) compartment, and the acquisition of a synthetic phenotype. Although the signals for vascular remodelling are diverse in different pathological contexts, SMC proliferation and migration are consistently observed. It is therefore critical to elucidate key mechanisms central to these processes. MicroRNAs (miRNAs) are small non-coding sequences of RNA that have the capacity to regulate many genes, pathways, and complex biological networks within cells, acting either alone or in concert with one another. In diseases such as cancer and cardiac disease, the role of miRNA in disease pathogenesis has been documented in detail. In contrast, despite a great deal of interest in miRNA, relatively few studies have directly assessed the role of miRNA in vascular remodelling. The potential for modulation of miRNA to achieve therapeutic benefits in this setting is attractive. Here, we focus on the role of miRNA in vascular inflammation and remodelling associated with acute vascular injury (vein graft disease, angioplasty restenosis, and in-stent restenosis) as well as in vascular remodelling associated with the development of pulmonary arterial hypertension. PMID:22065733

  9. Left ventricular function in patients with ventricular arrhythmias and aortic valve disease

    SciTech Connect

    Santinga, J.T.; Kirsh, M.M.; Brady, T.J.; Thrall, J.; Pitt, B.

    1983-02-01

    Forty patients having aortic valve replacement were evaluated preoperatively for ventricular arrhythmia and left ventricular ejection fraction. Arrhythmias were classified as complex or simple using the Lown criteria on the 24-hour ambulatory electrocardiogram; ejection fractions were determined by radionuclide gated blood pool analysis and contrast angiography. The ejection fractions determined by radionuclide angiography were 59.1 +/- 13.1% for 26 patients with simple or no ventricular arrhythmias, and 43.9 +/- 20.3% for 14 patients with complex ventricular arrhythmias (p less than 0.01). Ejection fractions determined by angiography, available for 31 patients, were also lower in patients with complex ventricular arrhythmias (61.1 +/- 16.3% versus 51.4 +/- 13.4%; p less than 0.05). Seven of 9 patients showing conduction abnormalities on the electrocardiogram had complex ventricular arrhythmias. Eight of 20 patients with aortic stenosis had complex ventricular arrhythmias, while 2 of 13 patients with aortic insufficiency had such arrhythmias. It is concluded that decreased left ventricular ejection fraction, intraventricular conduction abnormalities, and aortic stenosis are associated with an increased frequency of complex ventricular arrhythmias in patients with aortic valve disease.

  10. Rest and exercise ventricular function in adults with congenital ventricular septal defects

    SciTech Connect

    Jablonsky, G.; Hilton, J.D.; Liu, P.P.; Morch, J.E.; Druck, M.N.; Bar-Shlomo, B.Z.; McLaughlin, P.R.

    1983-01-15

    Rest and exercise right and left ventricular function were compared using equilibrium gated radionuclide angiography in 19 normal sedentary control subjects and 34 patients with hemodynamically documented congenital ventricular septal defect (VSD). Gated radionuclide angiography was performed at rest and during each level of graded supine bicycle exercise to fatigue. Heart rate, blood pressure, maximal work load achieved, and right and left ventricular ejection fractions were assessed. The control subjects demonstrated an increase in both the left and right ventricular ejection fractions with exercise. All study groups failed to demonstrate an increase in ejection fraction in either ventricle with exercise. Furthermore, resting left ventricular ejection fraction in Groups 2 and 3 was lower than that in the control subjects and resting right ventricular ejection fraction was lower in Group 3 versus control subjects. Thus left and right ventricular function on exercise were abnormal in patients with residual VSD as compared with control subjects; rest and exercise left ventricular ejection fractions remained abnormal despite surgical closure of VSD in the remote past; resting left and right ventricular function was abnormal in patients with Eisenmenger's complex; lifelong volume overload may be detrimental to myocardial function.

  11. Impact of residual stretch and remodeling on collagen engagement in healthy and pulmonary hypertensive calf pulmonary arteries at physiological pressures.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Albietz, Joseph A; Stenmark, Kurt R; Qi, H Jerry; Shandas, Robin; Hunter, Kendall S

    2012-07-01

    Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries' histological changes, in vivo pressure-diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized. To further understand the mechanical behavior of the proximal PAs under physiological conditions, this study computed the residual stretch and the in vivo circumferential stretch state in the main pulmonary arteries in both control and hypertensive calves by using in vitro and in vivo artery geometry data, and modeled the impact of residual stretch and arterial remodeling on the in vivo circumferential stretch distribution and collagen engagement in the main pulmonary artery. We found that the in vivo circumferential stretch distribution in both groups was nonuniform across the vessel wall with the largest stretch at the outer wall, suggesting that collagen at the outer wall would engage first. It was also found that the circumferential stretch was more uniform in the hypertensive group, partially due to arterial remodeling that occurred during their hypoxic treatment, and that their onset of collagen engagement occurred at a higher pressure. It is concluded that the residual stretch and arterial remodeling have strong impact on the in vivo stretch state and the collagen engagement and thus the mechanical behavior of the main pulmonary artery in calves. PMID:22237861

  12. Biologics in dermatology: adverse effects.

    PubMed

    Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta

    2015-12-01

    Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. PMID:26147909

  13. The proposed role of plasma NT pro-brain natriuretic peptide in assessing cardiac remodelling in hypertensive African subjects

    PubMed Central

    Ojji, Dike B; Opie, Lionel H; Lecour, Sandrine; Lacerda, Lydia; Sliwa, Karen; Adeyemi, Olusoji M

    2014-01-01

    Summary Aim Although plasma NT-proBNP differentiates hypertension (HT) with or without left ventricular hypertrophy (LVH) from hypertensive heart failure (HHF), most of the published data are based on studies in Western populations. Also, most previous studies did not consider left ventricular (LV) diastolic function and right ventricular (RV) function. We therefore examined the relation between NT-proBNP on LV and RV remodelling in an African hypertensive cohort. Methods Subjects were subdivided into three groups after echocardiography: hypertensives without LVH (HT) (n = 83); hypertensives with LVH (HT+LVH) (n = 50); and those with hypertensive heart failure (HHF) (n = 77). Results Subjects with HHF had significantly higher NT-proBNP levels compared to the HT+LVH group (p < 0.0002). NT-proBNP correlated positively with right atrial area, an indirect measure of RV function. Conclusions NT-proBNP is proposed as a useful biomarker in differentiating hypertension with or without LVH from hypertensive heart failure in black hypertensive subjects. PMID:25629540

  14. [Ventricular Septal Perforation after Inferior Myocardial Infarction].

    PubMed

    Sato, Hisashi; Nakayama, Yoshihiro; Tanaka, Hideya; Takahashi, Baku

    2016-07-01

    We report a rare case of ventricular septal perforation (VSP) after inferior myocardial infarction. Surgical repair of VSP after inferior infarction is technically difficult because of its anatomical location. An 81-year-old female presented with dyspnea on the 8th day after percutaneous coronary intervention for acute inferior myocardial infarction. Echocardiography revealed a ventricular septal perforation. Urgent operation was performed. There was a VSP around the base of the ventricular septum. The myocardial infarction extended to the adjacent muscle of the mitral valve annulus. Two bovine pericardial patches were used in the left ventricular cavity. The patches were sewn on the mitral valve annulus which was the only normal tissue in the region. The 1st patch was used to close the VSP directly, and the 2nd patch was sutured to the normal myocardium to exclude the infracted area. No residual shunt flow was observed. The postoperative course was uneventful. PMID:27365060

  15. Ventricular repolarization measures for arrhythmic risk stratification

    PubMed Central

    Monitillo, Francesco; Leone, Marta; Rizzo, Caterina; Passantino, Andrea; Iacoviello, Massimo

    2016-01-01

    Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave (QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice. PMID:26839657

  16. Sequential Notch activation regulates ventricular chamber development

    PubMed Central

    D'Amato, Gaetano; Luxán, Guillermo; del Monte-Nieto, Gonzalo; Martínez-Poveda, Beatriz; Torroja, Carlos; Walter, Wencke; Bochter, Matthew S.; Benedito, Rui; Cole, Susan; Martinez, Fernando; Hadjantonakis, Anna-Katerina; Uemura, Akiyoshi; Jiménez-Borreguero, Luis J.; de la Pompa, José Luis

    2016-01-01

    Ventricular chambers are essential for the rhythmic contraction and relaxation occurring in every heartbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is poorly understood. We show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation, and later coordinates ventricular patterning and compaction with coronary vessel development to generate the mature chamber, through a temporal sequence of ligand signalling determined by the glycosyltransferase manic fringe (MFng). Early endocardial expression of MFng promotes Dll4–Notch1 signalling, which induces trabeculation in the developing ventricle. Ventricular maturation and compaction require MFng and Dll4 downregulation in the endocardium, which allows myocardial Jag1 and Jag2 signalling to Notch1 in this tissue. Perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies. PMID:26641715

  17. Arterial remodeling of basilar atherosclerosis in isolated pontine infarction.

    PubMed

    Feng, Chao; Hua, Ting; Xu, Yu; Liu, Xue-Yuan; Huang, Jing

    2015-04-01

    Isolated pontine infarctions are usually classified as paramedian pontine infarction (PPI) and lacunar pontine infarction (LPI). Although they have different shapes and locations, some recent studies proved that they might both be associated with basilar artery atherosclerosis in pathogenesis. This study aimed to explore the difference of basilar artery remodeling between two subtypes of pontine infarctions. Patients with PPI or LPI were scanned by High-resolution MRI (HR-MRI). The MR images of patients with basilar artery atherosclerosis were further analyzed to measure the vessel, lumen and wall areas at different segments of basilar arteries. Stenosis rate and remodeling index were calculated according to which arterial remodeling was divided into positive, intermediate and negative remodeling. Vascular risk factors and remodeling-related features were compared between PPI and LPI, and also between patients with and without positive remodeling. 34 patients with PPI and 21 patients with LPI had basilar artery atherosclerosis identified by HR-MRI. Positive remodeling was dominant in LPI group while in PPI group, three subtypes of remodeling were equal. Patients with positive remodeling had higher levels of low-density lipoprotein and homocysteine. Positive remodeling of basilar artery might reflect the low stability of basilar atherosclerotic plaques, which was more closely associated with LPI than PPI. PMID:25367406

  18. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling

    PubMed Central

    Broide, David H.

    2008-01-01

    Although histologic features of airway remodeling have been well characterized in asthma, the immunologic and inflammatory mechanisms that drive progression of asthma to remodeling are still incompletely understood. Conceptually, airway remodeling may be due to persistent inflammation and/or aberrant tissue repair mechanisms. It is likely that several immune and inflammatory cell types and mediators are involved in mediating airway remodeling. In addition, different features of airway remodeling are likely mediated by different inflammatory pathways. Several important candidate mediators of remodeling have been identified including TGF-β and Th2 cytokines (including IL-5 and IL-13), as well as VEGF, ADAM-33, and MMP-9. Mouse models of airway remodeling have provided important insight into potential mechanisms by which TGF-β activation of the Smad 2/3 signaling pathway may contribute to airway remodeling. Human studies have demonstrated that anti-IL-5 reduces levels of airway eosinophils expressing TGF-β, as well as levels of airway remodeling as assessed by bronchial biopsies. Further such studies confirming these observations, as well as alternate studies targeting additional individual cell types, cytokines, and mediators are needed in human subjects with asthma to determine the role of candidate mediators of inflammation on the development and progression of airway remodeling. PMID:18328887

  19. Ventricular Septal Defect from Takotsubo Syndrome

    PubMed Central

    Caplow, Julie; Quatromoni, Neha

    2016-01-01

    Takotsubo Syndrome is a transient condition characterized by left ventricular systolic dysfunction with apical akinesis/dyskinesis and ballooning. Although the prognosis with medical management is excellent in most cases, rare cases of serious complications can occur. We present here a case of a 71-year-old woman presenting with acute decompensated heart failure with initial findings consistent with a myocardial infarction, who was found instead to have an acute ventricular septal defect as a complication of Takotsubo Syndrome. PMID:27563471

  20. [Ventricular contractility: Physiology and clinical projection].

    PubMed

    Domenech, Raúl J; Parra, Víctor M

    2016-06-01

    The contractile state of the heart is the result of myocardial contractility, the intrinsic mechanism that regulates the force and the shortening of the ventricle and determines the ventricular ejection volume. However, the ejection volume is also modulated by ventricular preload (diastolic ventricular volume) and afterload (resistance to ejection). Accordingly, a decrease in contractility may be masked by changes in preload or afterload, maintaining a normal ejection volume and delaying the diagnosis of myocardial damage. Thus, it is necessary to develop a non-invasive method to measure contractility in the clinical practice. We review in this article the basic principles of cardiac contraction, the concept of contractility and its measurement with the ventricular pressure-volume loop, an experimental method that also measures most of the hemodynamic variables of the cardiac cycle including preload, afterload, ventricular work, ventricular lusitropy and arterial elastance. This method has been recently validated in cardiac patients and allows to evaluate the evolution of contractility in heart failure in a non invasive way. Although some modifications are still necessary, it will probably have an extensive use in practical cardiology in the near future. PMID:27598497

  1. Targeted disruption of the heat shock protein 20-phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy.

    PubMed

    Martin, Tamara P; Hortigon-Vinagre, Maria P; Findlay, Jane E; Elliott, Christina; Currie, Susan; Baillie, George S

    2014-01-01

    Phosphorylated heat shock protein 20 (HSP20) is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20-phosphodiesterase 4D (PDE4D) complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20-PDE4D interaction leads to attenuation of pathological cardiac remodelling. PMID:25426411

  2. Adversity and advancing nursing knowledge.

    PubMed

    Reed, Pamela G

    2008-04-01

    This column reports the theme of adversity addressed in reference to theoretical and metatheoretical considerations for advancing nursing knowledge. The development and content of three classic nursing theories are presented by Neuman representatives, and by theorists King and Roy. Topics for continued dialogue are identified as derived from the interface between philosophy of science issues and these theories. PMID:18378823

  3. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  4. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  5. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  6. Antidepressants and cardiovascular adverse events: A narrative review

    PubMed Central

    Nezafati, Mohammad Hassan; Vojdanparast, Mohammad; Nezafati, Pouya

    2015-01-01

    BACKGROUND Major depression or deterioration of previous mood disorders is a common adverse consequence of coronary heart disease, heart failure, and cardiac revascularization procedures. Therefore, treatment of depression is expected to result in improvement of mood condition in these patients. Despite demonstrated effects of anti-depressive treatment in heart disease patients, the use of some antidepressants have shown to be associated with some adverse cardiac and non-cardiac events. In this narrative review, the authors aimed to first assess the findings of published studies on beneficial and also harmful effects of different types of antidepressants used in patients with heart diseases. Finally, a new categorization for selecting antidepressants according to their cardiovascular effects was described. METHODS Using PubMed, Web of Science, SCOPUS, Index Copernicus, CINAHL, and Cochrane Database, we identified studies designed to evaluate the effects of depression and also using antidepressants on cardiovascular outcome. A 40 studies were finally assessed systematically. Among those eligible studies, 14 were cohort or historical cohort studies, 15 were randomized clinical trial, 4 were retrospective were case-control studies, 3 were meta-analyses and 2 animal studies, and 2 case studies. RESULTS According to the current review, we recommend to divide antidepressants into three categories based on the severity of cardiovascular adverse consequences including (1) the safest drugs including those drugs with cardio-protective effects on ventricular function, as well as cardiac conductive system including selective serotonin reuptake inhibitors, (2) neutralized drugs with no evidenced effects on cardiovascular system including serotonin-norepinephrine reuptake inhibitors, and (3) harmful drugs with adverse effects on cardiac function, hemodynamic stability, and heart rate variability including tricyclic antidepressants, serotonin antagonist and reuptake inhibitors

  7. Short-term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats

    PubMed Central

    LI, YAN; XUAN, YAN-HUA; LIU, SHUANG-SHUANG; DONG, JING; LUO, JIA-YING; SUN, ZHI-JUN

    2015-01-01

    Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055

  8. A dynamic zone defines interneuron remodeling in the adult neocortex

    PubMed Central

    Lee, Wei-Chung Allen; Chen, Jerry L.; Huang, Hayden; Leslie, Jennifer H.; Amitai, Yael; So, Peter T.; Nedivi, Elly

    2008-01-01

    The contribution of structural remodeling to long-term adult brain plasticity is unclear. Here, we investigate features of GABAergic interneuron dendrite dynamics and extract clues regarding its potential role in cortical function and circuit plasticity. We show that remodeling interneurons are contained within a “dynamic zone” corresponding to a superficial strip of layers 2/3, and remodeling dendrites respect the lower border of this zone. Remodeling occurs primarily at the periphery of dendritic fields with addition and retraction of new branch tips. We further show that dendrite remodeling is not intrinsic to a specific interneuron class. These data suggest that interneuron remodeling is not a feature predetermined by genetic lineage, but rather, it is imposed by cortical laminar circuitry. Our findings are consistent with dynamic GABAergic modulation of feedforward and recurrent connections in response to top-down feedback and suggest a structural component to functional plasticity of supragranular neocortical laminae. PMID:19066223

  9. Anaesthesia and right ventricular failure.

    PubMed

    Forrest, P

    2009-05-01

    Acute right ventricular (RV) failure has until recently received relatively little attention in the cardiology, critical care or anaesthesia literature. However, it is frequently encountered in cardiac surgical cases and is a significant cause of mortality in patients with severe pulmonary hypertension who undergo non-cardiac surgery. RV dysfunction may be primarily due to impaired RV contractility, or volume or pressure overload. In these patients, an increased pulmonary vascular resistance (PVR) or a decreased aortic root pressure may lead to RV ischaemia, resulting in a rapid, downward haemodynamic spiral. The key aspects of 'RV protection' in patients who are at risk of perioperative decompensation are prevention, detection and treatment aimed at reversing the underlying pathophysiology. Minimising PVR and maintaining systemic blood pressure are of central importance in the prevention of RV decompensation, which is characterised by a rising central venous pressure and a falling cardiac output. Although there are no outcome data to support any therapeutic strategy for RV failure when PVR is elevated, the combination of inhaled iloprost or intravenous milrinone with oral sildenafil produces a synergistic reduction in PVR, while sparing systemic vascular resistance. Levosimendan is a promising new inotrope for the treatment of RV failure, although its role in comparison to older agents such as dobutamine, adrenaline and milrinone has yet to be determined. This is also the case for the use of vasopressin as an alternative pressor to noradrenaline. If all else has failed, mechanical support of the RV should be considered in selected cases. PMID:19499856

  10. Electrohydraulic ventricular assist device development.

    PubMed

    Diegel, P D; Mussivand, T; Holfert, J W; Juretich, J T; Miller, J A; Maclean, G K; Szurmak, Z; Santerre, J P; Rajagopalan, K; Dew, P A

    1992-01-01

    An electrohydraulic ventricular assist device has been developed. An axial flow pump driven by a brushless DC motor provides actuation. Energy is supplied by internal Ni/Cd batteries and by external Ag/Zn batteries, both rechargeable. Electromagnetic induction is used to pass energy through the skin with a transcutaneous energy transfer (TET) system. Physiologic control, battery management, motor commutation, and communication functions are performed by a surface mount internal controller. An infrared data link within the TET coils provides bidirectional communication between the external and internal controllers. A computer model was developed to predict system performance. The dimensions are 180 mm x 116 mm x 40 mm. An in vitro system pumped 5.7 L/min at 10 mmHg inflow and 100 mmHg outflow pressure. The internal battery can provide the projected energy requirements for 40 min after 540 charge/discharge cycles, and the external battery is capable of 4 hr of operation after 150 cycles. The TET system can deliver 60 W of power and exceeds 80% efficiency between 15 and 30 W. The device configuration is based on human cadaver and intraoperative fit trials. The device is being modified for calf implantation by redirecting the blood ports, increasing the output, and incorporating the internal controller in the unified device base. PMID:1457871

  11. Synchronized defibrillation for ventricular fibrillation

    PubMed Central

    Manoharan, Ganesh; Navarro, Cesar; Walsh, Simon J; Allen, John D; Anderson, John McC; Adgey, AA Jennifer

    2012-01-01

    Objective: Optimization of defibrillation success is important to improve efficacy and minimize post-shock sequelae. Previous work has suggested an improvement in shock success when an intracardiac shock is delivered synchronized to the upslope of a VF wave. We investigated the efficacy of transthoracic defibrillation success using a novel external biphasic defibrillator which delivers shocks synchronized to the upslope of the surface ECG. Methods: A prospective, controlled, randomized study in a research institute laboratory of male and female pigs (54.2±1.8 kg). Ventricular fibrillation (VF) was induced in 10 anaesthetized and ventilated pigs. Shocks were delivered randomly from a biphasic defibrillator in synchronized or non-synchronized mode via self-adhesive electrode pads following 30 s of VF. Energy settings at 50, 70, 80, and 100J were randomly tested. VF amplitude, impedance, and shock outcome were recorded and analysed digitally. Results: A total of 300 shocks were delivered. Synchronized shocks were delivered on the upslope of the VF wave in 99% of cases. There was no significant difference in shock success between shocks delivered in synchronized or non-synchronized modes (p=0.695). There was no significant difference in the amplitude of VF between successful and unsuccessful shocks (p=0.163). Furthermore, there was no association between shock success and transthoracic impedance. Conclusion: The novel defibrillator used in this study was able to consistently deliver shocks on the upslope portion of the VF wave but did not show an improvement in shock success. PMID:24062919

  12. Implication of Right Ventricular Dysfunction on Long-term Outcome in Patients with Ischemic Cardiomyopathy Undergoing Coronary Artery Bypass Grafting with or without Surgical Ventricular Reconstruction

    PubMed Central

    Kukulski, Tomasz; She, Lilin; Racine, Normand; Gradinac, Sinisa; Panza, Julio A.; Velazquez, Eric J.; Chan, Kwan; Petrie, Mark C.; Lee, Kerry L.; Pellikka, Patricia A.; Romanov, Alexander; Biernat, Jolanta; Rouleau, Jean L.; Batlle, Carmen; Rogowski, Jan; Ferrazzi, Paolo; Zembala, Marian; Oh, Jae K.

    2014-01-01

    Background Whether right ventricular (RV) dysfunction affects clinical outcome after CABG with or without SVR is still unknown. Thus, the aim of the study was to assess the impact of RV dysfunction on clinical outcome in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG) with or without surgical ventricular reconstruction (SVR). Methods and Results Of 1,000 STICH patients with coronary artery disease (CAD), left ventricular (LV) ejection fraction (EF) ≤35% and anterior dysfunction randomized to undergo CABG or CABG + SVR, baseline RV function could be assessed by echocardiography in 866 patients. Patients were followed for a median of 48 months. All-cause mortality or cardiovascular hospitalization was the primary endpoint, and all-cause mortality alone was a secondary endpoint. RV dysfunction was mild in 102 (12%) patients and moderate or severe in 78 (9%) patients. Moderate to severe RV dysfunction was associated with larger LV, lower EF, more severe mitral regurgitation, higher filling pressure, and higher pulmonary artery systolic pressure (all p<0.0001) compared to normal or mildly reduced RV function. A significant interaction between RV dysfunction and treatment allocation was observed. Patients with moderate or severe RV dysfunction who received CABG + SVR had significantly worse outcomes compared to patients who received CABG alone on both the primary (HR=1.86; CI=1.06–3.26; p=0.028) and the secondary endpoint (HR=3.37; CI=1.36–8.37; p=0.005). After adjusting for all other prognostic clinical factors, the interaction remained significant with respect to all-cause mortality (p=0.022). Conclusion Adding SVR to CABG may worsen long-term survival in ischemic cardiomyopathy patients with moderate to severe RV dysfunction, which reflects advanced LV remodeling. PMID:25451487

  13. Left ventricular function: time-varying elastance and left ventricular aortic coupling.

    PubMed

    Walley, Keith R

    2016-01-01

    Many aspects of left ventricular function are explained by considering ventricular pressure-volume characteristics. Contractility is best measured by the slope, Emax, of the end-systolic pressure-volume relationship. Ventricular systole is usefully characterized by a time-varying elastance (ΔP/ΔV). An extended area, the pressure-volume area, subtended by the ventricular pressure-volume loop (useful mechanical work) and the ESPVR (energy expended without mechanical work), is linearly related to myocardial oxygen consumption per beat. For energetically efficient systolic ejection ventricular elastance should be, and is, matched to aortic elastance. Without matching, the fraction of energy expended without mechanical work increases and energy is lost during ejection across the aortic valve. Ventricular function curves, derived from ventricular pressure-volume characteristics, interact with venous return curves to regulate cardiac output. Thus, consideration of ventricular pressure-volume relationships highlight features that allow the heart to efficiently respond to any demand for cardiac output and oxygen delivery. PMID:27613430

  14. Cardiac Metastasis of Leiomyosarcoma Complicated with Complete Atrio-Ventricular Block and Ventricular Tachycardia

    PubMed Central

    Shin, Jae Ouk; Kim, Minsu; Kang, Woong Chol; Moon, Jeonggeun; Chung, Wook-Jin; Sung, Yon Mi

    2016-01-01

    We described a case of a 54-year-old male who presented with dizziness and dyspnea due to cardiac metastasis of leiomyosarcoma. Cardiac metastasis of leiomyosarcoma caused both bradyarrhythmia and tachyarrhythmia in the patient. He was treated with implantation of a permanent pacemaker for management of complete atrio-ventricular block and anti-arrhythmic drug that suppressed ventricular tachycardia successfully. PMID:27014358

  15. Mitral subannular left ventricular aneurysm. A case presenting with ventricular tachycardia.

    PubMed Central

    Fitchett, D H; Kanji, M

    1983-01-01

    A young African immigrant presented with ventricular tachycardia in association with two mitral subannular left ventricular aneurysms. Although an unusual finding, the recognition of such aneurysms is important as prophylactic measures may prevent complications. Furthermore, they are a surgically treatable cause of heart failure and arrhythmias. Images PMID:6652004

  16. In Brief: Picturing the complex world of chromatin remodelling families.

    PubMed

    Witkowski, Leora; Foulkes, William D

    2015-12-01

    Over the past decade, chromatin remodelling emerged as one of the most important causes of both abnormal development and cancer. Although much has been written about one or another of the complexes, no recent concise summary of the chromatin remodelling families as a whole is available. In this short review, we introduce the family members, briefly summarize their role in developmental abnormalities and neoplasia, and outline the different ways in which these families remodel chromatin. PMID:26174723

  17. Control of bone remodelling by applied dynamic loads

    NASA Technical Reports Server (NTRS)

    Lanyon, L. E.; Rubin, C. T.

    1984-01-01

    The data showing the relationship between bone mass and peak strain magnitude prepared and submitted for publication. The data from experiments relating remodelling activity with static or dynamic loads were prepared and submitted for publication. Development of programs to relate the location of remodelling activity with he natural and artificial dynamic strain distributions continued. Experiments on the effect of different strain rates on the remodelling response continued.

  18. Pregnancy-induced remodeling of heart valves.

    PubMed

    Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M

    2015-11-01

    Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves. PMID:26371175

  19. Exercise thallium testing in ventricular preexcitation

    SciTech Connect

    Archer, S.; Gornick, C.; Grund, F.; Shafer, R.; Weir, E.K.

    1987-05-01

    Ventricular preexcitation, as seen in Wolff-Parkinson-White syndrome, results in a high frequency of positive exercise electrocardiographic responses. Why this occurs is unknown but is not believed to reflect myocardial ischemia. Exercise thallium testing is often used for noninvasive assessment of coronary artery disease in patients with conditions known to result in false-positive electrocardiographic responses. To assess the effects of ventricular preexcitation on exercise thallium testing, 8 men (aged 42 +/- 4 years) with this finding were studied. No subject had signs or symptoms of coronary artery disease. Subjects exercised on a bicycle ergometer to a double product of 26,000 +/- 2,000 (+/- standard error of mean). All but one of the subjects had at least 1 mm of ST-segment depression. Tests were terminated because of fatigue or dyspnea and no patient had chest pain. Thallium test results were abnormal in 5 patients, 2 of whom had stress defects as well as abnormally delayed thallium washout. One of these subjects had normal coronary arteries on angiography with a negative ergonovine challenge, and both had normal exercise radionuclide ventriculographic studies. Delayed thallium washout was noted in 3 of the subjects with ventricular preexcitation and normal stress images. This study suggests that exercise thallium testing is frequently abnormal in subjects with ventricular preexcitation. Ventricular preexcitation may cause dyssynergy of ventricular activation, which could alter myocardial thallium handling, much as occurs with left bundle branch block. Exercise radionuclide ventriculography may be a better test for noninvasive assessment of coronary artery disease in patients with ventricular preexcitation.

  20. Bacterial genome remodeling through bacteriophage recombination.

    PubMed

    Menouni, Rachid; Hutinet, Geoffrey; Petit, Marie-Agnès; Ansaldi, Mireille

    2015-01-01

    Bacteriophages co-exist and co-evolve with their hosts in natural environments. Virulent phages lyse infected cells through lytic cycles, whereas temperate phages often remain dormant and can undergo lysogenic or lytic cycles. In their lysogenic state, prophages are actually part of the host genome and replicate passively in rhythm with host division. However, prophages are far from being passive residents: they can modify or bring new properties to their host. In this review, we focus on two important phage-encoded recombination mechanisms, i.e. site-specific recombination and homologous recombination, and how they remodel bacterial genomes. PMID:25790500

  1. Impaired Glutathione Redox System Paradoxically Suppresses Angiotensin II-Induced Vascular Remodeling

    PubMed Central

    Izawa, Kazuma; Okada, Motoi; Sumitomo, Kazuhiro; Nakagawa, Naoki; Aizawa, Yoshiaki; Kawabe, Junichi; Kikuchi, Kenjiro; Hasebe, Naoyuki

    2014-01-01

    Background Angiotensin II (AII) plays a central role in vascular remodeling via oxidative stress. However, the interaction between AII and reduced glutathione (GSH) redox status in cardiovascular remodeling remains unknown. Methods In vivo: The cuff-induced vascular injury model was applied to Sprague Dawley rats. Then we administered saline or a GSH inhibitor, buthionine sulfoximine (BSO, 30 mmol/L in drinking water) for a week, subsequently administered 4 more weeks by osmotic pump with saline or AII (200 ng/kg/minute) to the rats. In vitro: Incorporation of bromodeoxyuridine (BrdU) was measured to determine DNA synthesis in cultured rat vascular smooth muscle cells (VSMCs). Results BSO reduced whole blood GSH levels. Systolic blood pressure was increased up to 215±4 mmHg by AII at 4 weeks (p<0.01), which was not affected by BSO. Superoxide production in vascular wall was increased by AII and BSO alone, and was markedly enhanced by AII+BSO. The left ventricular weight to body weight ratio was significantly increased in AII and AII+BSO as compared to controls (2.52±0.08, 2.50±0.09 and 2.10±0.07 mg/g respectively, p<0.05). Surprisingly, the co-treatment of BSO totally abolished these morphological changes. Although the vascular circumferential wall stress was well compensated in AII, significantly increased in AII+BSO. The anti-single-stranded DNA staining revealed increasing apoptotic cells in the neointima of injured arteries in BSO groups. BrdU incorporation in cultured VSMCs with AII was increased dose-dependently. Furthermore it was totally abolished by BSO and was reversed by GSH monoethyl ester. Conclusions We demonstrated that a vast oxidative stress in impaired GSH redox system totally abolished AII-induced vascular, not cardiac remodeling via enhancement of apoptosis in the neointima and suppression of cell growth in the media. The drastic suppression of remodeling may result in fragile vasculature intolerable to mechanical stress by AII. PMID

  2. Structural remodeling of the heart and its premotor cardioinhibitory vagal neurons following T5 spinal cord transection

    PubMed Central

    Lujan, Heidi L.; Janbaih, Hussein

    2014-01-01

    Midthoracic spinal cord injury (SCI) is associated with enhanced cardiac sympathetic activity and reduced cardiac parasympathetic activity. The enhanced cardiac sympathetic activity is associated with sympathetic structural plasticity within the stellate ganglia, spinal cord segments T1–T4, and heart. However, changes to cardiac parasympathetic centers rostral to an experimental SCI are relatively unknown. Importantly, reduced vagal activity is a predictor of high mortality. Furthermore, this autonomic dysregulation promotes progressive left ventricular (LV) structural remodeling. Accordingly, we hypothesized that midthoracic spinal cord injury is associated with structural plasticity in premotor (preganglionic parasympathetic neurons) cardioinhibitory vagal neurons located within the nucleus ambiguus as well as LV structural remodeling. To test this hypothesis, dendritic arborization and morphology (cholera toxin B immunohistochemistry and Sholl analysis) of cardiac projecting premotor cardioinhibitory vagal neurons located within the nucleus ambiguus were determined in intact (sham transected) and thoracic level 5 transected (T5X) rats. In addition, LV chamber size, wall thickness, and collagen content (Masson trichrome stain and structural analysis) were determined. Midthoracic SCI was associated with structural changes within the nucleus ambiguus and heart. Specifically, following T5 spinal cord transection, there was a significant increase in cardiac parasympathetic preganglionic neuron dendritic arborization, soma area, maximum dendritic length, and number of intersections/animal. This parasympathetic structural remodeling was associated with a profound LV structural remodeling. Specifically, T5 spinal cord transection increased LV chamber area, reduced LV wall thickness, and increased collagen content. Accordingly, results document a dynamic interaction between the heart and its parasympathetic innervation. PMID:24610530

  3. Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling

    PubMed Central

    2010-01-01

    Background Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9). Results Molecular modeling and LIGPLOT analysis revealed in silico docking of SalB at the catalytic site of MMP-9. Following this lead, we expressed truncated MMP-9 which contains only the catalytic domain, and used this active protein for in-gel gelatin zymography, enzymatic analysis, and SalB binding by Biacore. Data generated from these assays indicated that SalB functioned as a competitive inhibitor of MMP-9. In our rat model for cardiac remodeling, western blot, echocardiography, hemodynamic measurement and histopathological detection were used to detect the effects and mechanism of SalB on cardio-protection. Our results showed that in MI rat, SalB selectively inhibited MMP-9 activities without affecting MMP-9 expression while no effect of SalB was seen on MMP-2. Moreover, SalB treatment in MI rat could efficiently increase left ventricle wall thickness, improve heart contractility, and decrease heart fibrosis. Conclusions As a competitive inhibitor of MMP-9, SalB presents significant effects on preventing LV structural damage and preserving cardiac function. Further studies to develop SalB and its analogues for their potential for cardioprotection in clinic are warranted. PMID:20735854

  4. Dynamic Changes of QRS Morphology of Premature Ventricular Contractions During Ablation in the Right Ventricular Outflow Tract: A Case Report.

    PubMed

    Yue-Chun, Li; Jia-Feng, Lin; Jia-Xuan, Lin

    2015-10-01

    Electrocardiographic characteristics can be useful in differentiating between right ventricular outflow tract (RVOT) and aortic sinus cusp (ASC) ventricular arrhythmias. Ventricular arrhythmias originating from ASC, however, show preferential conduction to RVOT that may render the algorithms of electrocardiographic characteristics less reliable. Even though there are few reports describing ventricular arrhythmias with ASC origins and endocardial breakout sites of RVOT, progressive dynamic changes in QRS morphology of the ventricular arrhythmias during ablation obtained were rare.This case report describes a patient with symptomatic premature ventricular contractions of left ASC origin presenting an electrocardiogram (ECG) characteristic of right ventricular outflow tract before ablation. Pacing at right ventricular outflow tract reproduced an excellent pace map. When radiofrequency catheter ablation was applied to the right ventricular outflow tract, the QRS morphology of premature ventricular contractions progressively changed from ECG characteristics of right ventricular outflow tract origin to ECG characteristics of left ASC origin.Successful radiofrequency catheter ablation was achieved at the site of the earliest ventricular activation in the left ASC. The distance between the successful ablation site of the left ASC and the site with an excellent pace map of the RVOT was 20 mm.The ndings could be strong evidence for a preferential conduction via the myocardial bers from the ASC origin to the breakout site in the right ventricular outflow tract. This case demonstrates that ventricular arrhythmias with a single origin and exit shift may exhibit QRS morphology changes. PMID:26496347

  5. Arterial load and ventricular-arterial coupling: physiologic relations with body size and effect of obesity.

    PubMed

    Chirinos, Julio A; Rietzschel, Ernst R; De Buyzere, Marc L; De Bacquer, Dirk; Gillebert, Thierry C; Gupta, Amit K; Segers, Patrick

    2009-09-01

    Accurate quantification of arterial function is crucial to distinguishing disease states from normal variants. However, there are little data regarding methods to scale arterial load to body size in humans. We studied 2365 adults aged 35 to 55 years free of overt cardiovascular disease. We assessed arterial hemodynamics and ventricular-vascular coupling with carotid tonometry and Doppler echocardiography. To define normal (physiological) relationships between hemodynamic indices and body size, we used nonlinear regression to analyze a selected reference subsample (n=612) with normal weight (body mass index 18 to 25 kg/m(2)), waist circumference, and metabolic parameters. Most arterial hemodynamic indices demonstrated important relationships with body size, which were frequently allometric (nonlinear). Allometric indexation using appropriate powers (but not ratiometric indexation) effectively eliminated the relationships between indices of arterial load and body size in normal subjects. In the entire sample (n=2365), the adverse effects of obesity on arterial load and end-systolic ventricular stiffening were clearly demonstrated only after appropriate indexation to account for the expected normal relationship to body size. After adjustment for age and sex, a progressive increase in indexed systemic vascular resistance, effective arterial and ventricular end-systolic elastance, and a decrease in total arterial compliance were seen from normal weight to obesity (P<0.0001). Arterial load relates to body size in an allometric fashion, calling for scaling with the use of appropriate powers. Obesity exerts adverse effects on arterial load and ventricular stiffening that go beyond the normal relationship with body size. Allometric normalization should allow more accurate quantification of arterial load in future studies. PMID:19581507

  6. Low-Dose Bisphenol A and Estrogen Increase Ventricular Arrhythmias Following Ischemia-Reperfusion in Female Rat Hearts

    PubMed Central

    Yan, Sujuan; Song, Weizhong; Chen, Yamei; Hong, Kui; Rubinstein, Jack; Wang, Hong-Sheng

    2013-01-01

    Bisphenol A (BPA) is an environmental estrogenic endocrine disruptor that may have adverse health impacts on a range of tissue/systems. In previous studies, we reported that BPA rapidly promoted arrhythmias in female rodent hearts through alteration of myocyte calcium handling. In the present study we investigated the acute effects of BPA on ventricular arrhythmias and infarction following ischemia-reperfusion in rat hearts. Rat hearts were subjected to 20 minutes of global ischemia followed by reperfusion. In female, but not male hearts, acute exposure to 1 nM BPA, either alone or combined with 1 nM 17β-estradiol (E2), during reperfusion resulted in a marked increase in the duration of sustained ventricular arrhythmias. BPA plus E2 increased the duration ventricular fibrillation, and the duration of VF as a fraction of total duration of sustained ventricular arrhythmia. The pro-arrhythmic effects of estrogens were abolished by MPP combined with PHTPP, suggesting the involvements of both ERα and ERβ signaling. In contrast to their pro-arrhythmic effects, BPA and E2 reduced infarction size, agreeing with previously described protective effect of estrogen against cardiac infarction. In conclusion, rapid exposure to low dose BPA, particularly when combined with E2, exacerbates ventricular arrhythmia following IR injury in female rat hearts. PMID:23429042

  7. Advancing knowledge of right ventricular pathophysiology in chronic pressure overload: Insights from experimental studies.

    PubMed

    Guihaire, Julien; Noly, Pierre Emmanuel; Schrepfer, Sonja; Mercier, Olaf

    2015-10-01

    The right ventricle (RV) has to face major changes in loading conditions due to cardiovascular diseases and pulmonary vascular disorders. Clinical experience supports evidence that the RV better compensates for volume than for pressure overload, and for chronic than for acute changes. For a long time, right ventricular (RV) pathophysiology has been restricted to patterns extrapolated from left heart studies. However, the two ventricles are anatomically, haemodynamically and functionally distinct. RV metabolic properties may also result in a different behaviour in response to pathological conditions compared with the left ventricle. In this review, current knowledge of RV pathophysiology is reported in the setting of chronic pressure overload, including recent experimental findings and emerging concepts. After a time-varying compensated period with preserved cardiac output despite overload conditions, RV failure finally occurs, leading to death. The underlying mechanisms involved in the transition from compensatory hypertrophy to maladaptive remodelling are not completely understood. PMID:26184869

  8. Anatomical Substrates and Ablation of Reentrant Atrial and Ventricular Tachycardias in Repaired Congenital Heart Disease.

    PubMed

    Brouwer, Charlotte; Hazekamp, Mark G; Zeppenfeld, Katja

    2016-08-01

    Advances in surgical repair techniques for various types of congenital heart disease have improved survival into adulthood over the past decades, thus exposing these patients to a high risk of atrial and ventricular arrhythmias later in life. These arrhythmias arise from complex arrhythmogenic substrates. Substrate formation may depend on both pathological myocardial remodelling and variable anatomical boundaries, determined by the type and timing of prior corrective surgery. Accordingly, arrhythmogenic substrates after repair have changed as a result of evolving surgical techniques. Radiofrequency catheter ablation offers an important therapeutic option but remains challenging due to the variable anatomy, surgically created obstacles and the complex arrhythmogenic substrates. Recent technical developments including electroanatomical mapping and image integration for delineating the anatomy facilitate complex catheter ablation procedures. The purpose of this review is to provide an update on the changing anatomical arrhythmogenic substrates and their potential impact on catheter ablation in patients with repaired congenital heart disease and tachyarrhythmias. PMID:27617095

  9. Anatomical Substrates and Ablation of Reentrant Atrial and Ventricular Tachycardias in Repaired Congenital Heart Disease

    PubMed Central

    Brouwer, Charlotte; Hazekamp, Mark G

    2016-01-01

    Advances in surgical repair techniques for various types of congenital heart disease have improved survival into adulthood over the past decades, thus exposing these patients to a high risk of atrial and ventricular arrhythmias later in life. These arrhythmias arise from complex arrhythmogenic substrates. Substrate formation may depend on both pathological myocar