Effects of Voluntary Exercise on Viability and Electrical Remodeling in DCN Model Mice

Abstract

A moderate amount of exercise has been reported to improve the symptom of heart failure (HF). Dilated cardiomyopathy (DCM) is one of major causes of HF characterized by ventricular dilatation and contractile dysfunction, and often associated with sudden death (SD) by lethal arrhythmia. Applicability of exercise to DCM patients is not established yet. In this study, we evaluated effects of voluntary exercise on arrhythmogenic changes in a mouse model of inherited DCM that closely mimics human phenotype. Mice with a deletion mutation of K210 (ΔK210) in cardiac troponin T, which decreases Ca2+ sensitivity in myofilaments, were used as DCM model. Wild type (WT) and DCM mice at various ages were housed with free access to a running wheel and their voluntary running activity was measured. Ventricular muscles were excised and gene expressions of ion channels were determined by real-time PCR analysis.Membrane potential signals were optically determined to detect functional changes in myocardium. Homozygous ΔK210 mice developed cardiac enlargement and showed frequent SD with t1/2 of 70 days. Down regulation of multiple types of K+ channels was detected in DCM mice. In parallel, prolongation of action potential duration and frequent spontaneous activity were observed. At 2-month of age, DCM mice showed similar wheel-running activity to WT. Some of DCM mice at 3 months or later decreased running activity with lung edema. In DCM mice with high activity, down-regulation of K+ channels was less marked. The DCM mice that started running at a young age showed significantly improved survival rate. These results indicate that (1) running wheel was useful to detect sign of HF, and that (2) voluntary exercise is beneficial to DCM mice. Potential mechanisms contributing to the improved survival rate will be discussed.