The Benefits of Voluntaly Exersice on Cardiac Function in DCM Model Mice

Abstract

Dilated cardiomyopathy (DCM) is a progressive disease characterized by ventricular dilatation and contractile dysfunction. DCM patients often die with chronic heart failure (50%) or lethal arrhythmia (30∼40%). To date, the exercise is considered to be one of therapy for HF, but the effects of exercise on DCM patients are still unclear. In this study, we examined effects of exercise on progression of HF and arrhythmogenicity in DCM using a DCM mouse model that closely mimics human inherited DCM.We used a knock-in mouse model having human DCM mutation, TNNT2 ΔK210, which decreases Ca2+ sensitivity of myofilaments. HomozygousΔK210 (DCM) mice and wild type (WT) mice at 1 month-old were housed with a running wheel (diameter = 12 cm) continuously or intermittently, and daily voluntary running activity was recorded. At 2 and 3 month-old, end-diastolic dimension and ejection fraction (EF) were measured by echocardiography. Heart, lung and lower extremity muscle were excised and their weights were measured together with body weight. Gene expressions of markers for HF and major ion channels were quantified by q-PCR analysis.The control DCM mice without running exercise showed enlarged heart, frequent SD with t1/2 of 70 days, and lowered systolic cardiac function defined by the average EF. DCM mice with running exercise showed significantly improved survival rate and less marked cardiac enlargement with dose dependent manner. Moreover, the average EF was higher in DCM mice with exercise. These beneficial effects seem to be related to the amount of exercise assessed from lower extremity muscle weights. We also found that down-regulation of some K+ channels were partially suppressed in DCM mice with exercise. These results suggest that voluntary exercise started at young age may be beneficial to DCM patients.