Integrative Effect of Carvedilol and Aerobic Exercise Training Therapies on Improving Cardiac Contractility and Remodeling in Heart Failure Mice

Integrative Effect of Carvedilol and Aerobic Exercise Training Therapies on Improving Cardiac Contractility and Remodeling in Heart Failure Mice

Author Vanzelli, Andrea S. Google Scholar
Medeiros, Alessandra Autor UNIFESP Google Scholar
Rolim, Natale Google Scholar
Bartholomeu, Jan B. Google Scholar
Cunha, Telma F. Google Scholar
Bechara, Luiz G. Google Scholar
Gomes, Eneas R. M. Google Scholar
Mattos, Katt C. Google Scholar
Sirvente, Raquel Google Scholar
Salemi, Vera Google Scholar
Mady, Charles Google Scholar
Negrao, Carlos E. Google Scholar
Guatimosim, Silvia Google Scholar
Brum, Patricia C. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Dept Circulat & Med Imaging
KG Jebsen Ctr Exercise Med
Universidade Federal de Minas Gerais (UFMG)
Abstract The use of b-blockers is mandatory for counteracting heart failure (HF)-induced chronic sympathetic hyperactivity, cardiac dysfunction and remodeling. Importantly, aerobic exercise training, an efficient nonpharmacological therapy to HF, also counteracts sympathetic hyperactivity in HF and improves exercise tolerance and cardiac contractility; the latter associated with changes in cardiac Ca2+ handling. This study was undertaken to test whether combined b-blocker and aerobic exercise training would integrate the beneficial effects of isolated therapies on cardiac structure, contractility and cardiomyocyte Ca2+ handling in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha 2C(-)adrenergic receptor knockout mice, KO). We used a cohort of 5-7 mo male wild-type (WT) and congenic mice (KO) with C57Bl6/J genetic background randomly assigned into 5 groups: control (WT), saline-treated KO (KOS), exercise trained KO (KOT), carvedilol-treated KO (KOC) and, combined carvedilol-treated and exercise-trained KO (KOCT). Isolated and combined therapies reduced mortality compared with KOS mice. Both KOT and KOCT groups had increased exercise tolerance, while groups receiving carvedilol had increased left ventricular fractional shortening and reduced cardiac collagen volume fraction compared with KOS group. Cellular data confirmed that cardiomyocytes from KOS mice displayed abnormal Ca2+ handling. KOT group had increased intracellular peak of Ca2+ transient and reduced diastolic Ca2+ decay compared with KOS group, while KOC had increased Ca2+ decay compared with KOS group. Notably, combined therapies re-established cardiomyocyte Ca2+ transient paralleled by increased SERCA2 expression and SERCA2: PLN ratio toward WT levels. Aerobic exercise trained increased the phosphorylation of PLN at Ser16 and Thr17 residues in both KOT and KOCT groups, but carvedilol treatment reduced lipid peroxidation in KOC and KOCT groups compared with KOS group. the present findings provide evidence that the combination of carvedilol and aerobic exercise training therapies lead to a better integrative outcome than carvedilol or exercise training used in isolation.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
Conselho Nacional de Pesquisa e Desenvolvimento
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: FAPESP:2010/50048-1
FAPESP: 06/56123-0
CNPq: 302201/2011-4
Date 2013-05-01
Published in Plos One. San Francisco: Public Library Science, v. 8, n. 5, 8 p., 2013.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 8
Origin http://dx.doi.org/10.1371/journal.pone.0062452
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000319167000045
URI http://repositorio.unifesp.br/handle/11600/36250

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