Exercise training reduces ventricular arrhythmias through restoring calcium handling and sympathetic tone in myocardial infarction mice

Exercise can improve morbidity and mortality in heart failure patients; however, the underlying mechanisms remain to be fully investigated. Thus, we investigated the effects of exercise on cardiac function and ventricular arrhythmias in myocardial infarction (MI) induced heart failure mice. Wild-type male mice underwent sham-operation or permanent left coronary artery ligation to induce MI. MI mice were divided into a sedentary (MI-Sed) and two intervention groups: MI-Ex (underwent 6-week treadmill exercise training) and MI-βb (oral bisoprolol treatment (1 mg/kg/d) without exercise). Cardiac function and structure were assessed by echocardiography and histology. Exercise capacity and cardiopulmonary function was accepted as oxygen consumption at peak exercise (peak VO₂). Autonomic nervous system function and the incidence of spontaneous ventricular arrhythmia were evaluated via telemetry recording. mRNA and protein expressions in the left ventricle (LV) were investigated by real-time PCR and Western blotting. There were no differences in survival rate, MI size, cardiac function and structure, while exercise training improved peak VO₂. Compared with MI-Sed, MI-Ex, and MI-βb showed decreased sympathetic tone and lower incidence of spontaneous ventricular arrhythmia. By Western blot, the hyperphosphorylation of CaMKII and RyR2 were restored by exercise and β-blocker treatment. Furthermore, elevated expression of miR-1 and decreased expression of its target protein PP2A were recovered by exercise and β-blocker treatment. Continuous intensive exercise training can suppress ventricular arrhythmias in subacute to chronic phase of MI through restoring autonomic imbalance and impaired calcium handling, similarly to that for β-blockers.