Exercise training improves cardiac autonomic control, cardiac function, and arrhythmogenesis in rats with preserved-ejection fraction heart failure

Abstract

Chronic heart failure is characterized by autonomic imbalance, cardiac dysfunction, and arrhythmogenesis. It has been shown that exercise training (ExT) improves central nervous system oxidative stress, autonomic control, and cardiac function in heart failure with reduced ejection fraction; however, to date no comprehensive studies have addressed the effects of ExT, if any, on oxidative stress in brain stem cardiovascular areas, cardiac autonomic balance, arrhythmogenesis, and cardiac function in heart failure with preserved ejection fraction (HFpEF). We hypothesize that ExT reduces brain stem oxidative stress, improves cardiac autonomic control and cardiac function, and reduces arrhythmogenesis in HFpEF rats. Rats underwent sham treatment or volume overload to induce HFpEF. ExT (60 min/day, 25 m/min, 10% inclination) was performed for 6 wk starting at the second week after HFpEF induction. Rats were randomly allocated into Shamsedentary (Sed) (n 8), ShamExT (n 6), HFpEFSed (n 8), and HFpEFExT (n 8) groups. Compared with the HFpEFSed condition, HFpEFExT rats displayed reduced NAD(P)H oxidase activity and oxidative stress in the rostral ventrolateral medulla (RVLM), improved cardiac autonomic balance, and reduced arrhythmogenesis. Furthermore, a threefold improvement in cardiac function was observed in HFpEFExT rats. These novel findings suggest that moderate-intensity ExT is an effective means to attenuate the progression of HFpEF through improvement in RVLM redox state, cardiac autonomic control, and cardiac function.