Chronic therapy with metoprolol attenuates cardiomyocyte apoptosis in dogs with heart failure

Sabbah, Hani N.; Sharov, Victor G.; Gupta, Ramesh C.; Todor, Anastassia; Singh, Vijay; Goldstein, Sidney

doi:10.1016/s0735-1097(00)00913-x

Cited by 98 publications

(56 citation statements)

References 25 publications

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“…The slight amount of apoptotic cardiomyocyte nuclei, which is unlikely to account for the observed dysfunction, is consistent with prior studies. 27 In addition, sphingosine contents were increased, consistent with prior studies that found increased sphingosine content in myocardium on TNF-␣ stimulation. 12,28,29 Intracoronary pretreatment with L-NAME completely prevented the progressive myocardial contractile dysfunction, and TNF-␣ and sphingosine contents were no longer increased, indicating that NO acted upstream from TNF-␣ and sphingosine.…”

Section: Discussionsupporting

confidence: 88%

Myocardial Dysfunction With Coronary Microembolization

Thielmann

Dörge

Martin

et al. 2002

Circulation Research

171

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Abstract-Coronary microembolization results in progressive myocardial dysfunction, with causal involvement of tumor necrosis factor-␣ (TNF-␣). TNF-␣ uses a signal transduction involving nitric oxide (NO) and/or sphingosine. Therefore, we induced coronary microembolization in anesthetized dogs and studied the role and sequence of NO, TNF-␣, and sphingosine for the evolving contractile dysfunction. Four sham-operated dogs served as controls (group 1). Eleven dogs received placebo (group 2), 6 dogs received the NO synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME, group 3), and 6 dogs received the ceramidase inhibitor N-oleoylethanolamine (NOE, group 4) before microembolization was induced by infusion of 3000 microspheres (42-m diameter) per milliliter inflow into the left circumflex coronary artery. Posterior systolic wall thickening (PWT) remained unchanged in group 1 but decreased progressively in group 2 from 20.6Ϯ4.9% (meanϮSD) at baseline to 4.1Ϯ3.7% at 8 hours after microembolization. Leukocyte count, TNF-␣, and sphingosine contents were increased in the microembolized posterior myocardium. In group 3, PWT remained unchanged (20.3Ϯ2.6% at baseline) with intracoronary administration of L-NAME (20.8Ϯ3.4%) and 17.7Ϯ2.3% at 8 hours after microembolization; TNF-␣ and sphingosine contents were not increased. In group 4, PWT also remained unchanged (20.7Ϯ4.6% at baseline) with intravenous administration of NOE (19.5Ϯ5.7%) and 16.4Ϯ6.3% at 8 hours after microembolization; TNF-␣, but not sphingosine content, was increased. In all groups, systemic hemodynamics, anterior systolic wall thickening, and regional myocardial blood flow remained unchanged throughout the protocols. A signal transduction cascade of NO, TNF-␣, and sphingosine is causally involved in the coronary microembolizationinduced progressive contractile dysfunction.

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Section: Discussionsupporting

confidence: 88%

Myocardial Dysfunction With Coronary Microembolization

Thielmann

Dörge

Martin

et al. 2002

Circulation Research

171

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“…In support of this hypothesis, a previous study of patients with dilated cardiomyopathy taking ␤-blockers showed an inverse relationship between the amount of replacement fibrosis present on endomyocardial biopsy and amount of improvement in LVEF with therapy. 18 In addition to improvement in energetics, reduction in ischemia, and a shift in phenotype, which may lead to improved function, ␤-blockers may slow the rate of myocyte apoptosis, 19 thus preserving myocardial contractile reserve.…”

Section: Discussionmentioning

confidence: 99%

Myocardial Contractile Reserve by Dobutamine Stress Echocardiography Predicts Improvement in Ejection Fraction With β-Blockade in Patients With Heart Failure

et al. 2003

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MS; for the BEST InvestigatorsBackground-␤-Blockers improve survival and reduce hospitalization in chronic heart failure (CHF) by biologically improving left ventricular ejection fraction (LVEF). However, a good predictor of improvement with this therapy has not been identified. This substudy of BEST examined whether myocardial contractile reserve, as determined by dobutamine stress echocardiography, predicts improvement in LVEF. Methods and Results-Seventy-nine patients with class III/IV CHF underwent dobutamine stress echocardiography before treatment with bucindolol (nϭ41) or placebo (nϭ38). Regional wall motion score index (WMSI) was calculated as the sum of the scores in each segment divided by the total number of segments visualized. WMSI was compared with change in LVEF after 3 months of therapy as determined by gated radionuclide scan. Change in WMSI correlated inversely with change in LVEF after 3 months of bucindolol (rϭϪ0.72, PϽ0.0001) and was the most significant multivariate predictor of change in LVEF (Pϭ0.0002). Patients with contractile reserve had demographics similar to those of patients without contractile reserve, including RVEF, LVEF, systolic blood pressure, and CHF duration. However, patients without contractile reserve had higher baseline plasma norepinephrine levels (687Ϯ333 versus 420Ϯ246 pg/mL, PϽ0.05) and greater decrease in plasma norepinephrine in response to bucindolol (Ϫ249Ϯ171 versus Ϫ35Ϯ277 pg/mL, PϽ0.05). Conclusions-This study suggests a direct relationship between contractile reserve and improvement in LVEF with ␤-blocker therapy in patients with advanced CHF. Patients without contractile reserve have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may experience greater sympatholytic effects from bucindolol.

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“…However, beta-blockers also had various side effects and limitations and it is not easy to increase the dose of a beta-blocker for HR reduction. In addition, betablockade has other protective effects for HF such as attenuating apoptosis 39,40) and improving adrenergic signal transduction. 41,42) Thus, decreased HR in beta-blocker use may be an epiphenomenon or the consequence of an improved status of HF.…”

Section: Discussionmentioning

confidence: 99%

Incidence and Predictors of Rehospitalization of Acute Heart Failure Patients

et al. 2015

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SummaryRepeated hospitalization due to acute decompensated heart failure (HF) is a pandemic health problem in Japan. However, it is difficult to predict rehospitalization after discharge for acute decompensated HF. We used a single hospital-based cohort from the Shinken Database 2004Database -2012 who visited the Cardiovascular Institute Hospital. A total of 282 patients discharged after their first acute HF admission were included in the analysis. The median follow-up period was 908 ± 865 days. Of these patients, rehospitalization due to worsening HF occurred in 55 patients. The cumulative rate of rehospitalization was 17.5% at 1 year, 21.4% at 2 years, and 25.5% at 3 years. Patients with rehospitalization were older than those without rehospitalization. Prevalence of diabetes mellitus (DM) was more common in patients with rehospitalization. Average heart rate (HR) tended to be higher in patients with rehospitalization. Loop diuretics were more commonly used at hospital discharge in patients with rehospitalization. Multivariate Cox regression analysis revealed that age ≥ 75 years, DM, HR ≥ 75 bpm at discharge, and use of loop diuretics at discharge were independent predictors for rehospitalization. The number of these independent risk factors could be used to clearly discriminate between the HF rehospitalization low-, middle-and high-risk patients. HF rehospitalization commonly occurred in patients who were discharged after their first acute HF admission. Older age, DM, increased HR, and loop diuretics use at discharge were independently associated with HF rehospitalization. By simply counting these risk factors, we might be able to predict the risk of HF rehospitalization after discharge. (Int Heart J 2015; 56: 219-225)

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Chronic therapy with metoprolol attenuates cardiomyocyte apoptosis in dogs with heart failure

Abstract: Chronic therapy with MET attenuates cardiomyocyte apoptosis in dogs with moderate HF. Attenuation of ongoing cardiomyocyte loss through apoptosis may be one mechanism through which beta-blockers elicit their benefits in HF.

Cited by 98 publications

References 25 publications

Myocardial Dysfunction With Coronary Microembolization

Myocardial Dysfunction With Coronary Microembolization

Myocardial Contractile Reserve by Dobutamine Stress Echocardiography Predicts Improvement in Ejection Fraction With β-Blockade in Patients With Heart Failure

Incidence and Predictors of Rehospitalization of Acute Heart Failure Patients

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