Aerobic Interval Training Prevents Cardiac Dysfunction and Mortality by Improving Calcium Handling in MI Diabetic Mice

Abstract

Diabetic patients have greater risk of developing congestive heart failure (HF) after myocardium infarction (MI). Exercise training is an effective strategy for preventing the development of cardiomyopathies and the incidence of cardiovascular morbidity and mortality during diabetes.Aim - To study the effects of aerobic interval training (AIT) on cardiac function and the role of calcium handling in a combined experimental model of MI-induced HF and diabetic cardiomyopathy.Methods and Results - A cohort of male diabetic db/db and age-matched nondiabetic control mice was randomly assigned into untrained and trained sham and MI groups. MI was induced by coronary ligation. Exercise tolerance was evaluated by VO2 max. Standard echocardiography and tissue Doppler imaging were performed by high-resolution in-vivo imaging system, and diastolic sarcoplasmic reticulum (SR) calcium leak was measured in isolated cardiomyocytes using fluorescence microscope. MI diabetic mice displayed higher mortality rate compared to MI nondiabetic and sham mice (55% vs. 25% and 0%, respectively). In addition, exercise intolerance, reduced fractional shortening (FS), and cardiomyocyte dysfunction were observed in MI diabetic mice compared to other groups. AIT increased survival rate and exercise tolerance in MI diabetic to diabetic sham levels, paralleled by increased FS. AIT reestablished contractile function of MI diabetic to diabetic sham levels associated with improved SR calcium release synchronicity, T-tubule density and SR calcium leak.Conclusion - These results provide evidence for improvement of calcium handling by AIT in MI-induced HF during diabetes. Therefore, AIT is a potential therapeutic tool for the management of HF associated with diabetes.