Cardiomyocyte Calcium Handling Dysfunction at High Stimulation Frequencies; Increase in Post-Myocardial Infarction Heart Failure and Decrease by Exercise Training

Abstract

Ca2+ transient alternans, ie incomplete 1:2 Ca2+ transients, have been linked to contractile dysfunction at high heart rates in heart failure (HF). We investigated the effect of post-myocardial infarction (MI) HF and the therapeutic effect of exercise training on cardiomyocyte Ca2+ handling during increased electrical twitch-stimulation frequencies, in coronary artery-ligated Wistar rats. 4-weeks post-surgery, aerobic exercise training was initiated, with sham-operated (SHAM) and sedentary MI HF rats as controls. MI HF was confirmed by reduced exercise capacity, pathologic cardiomyocyte hypertrophy, and reduced cardiomyocyte contraction and Ca2+ transient amplitude (all 20-40%; p 0.05 vs MI HF), but it shifted the occurrence of Ca2+ transient alternans to higher twitch-stimulation frequencies (median frequency SHAM: 4Hz, MI HF 2Hz, MI HF after exercise training 4Hz; p<0.05). Finally, Ca2+ transient alternans magnitude (difference 1:2 Ca2+ transient) increased in MI HF cardiomyocytes (25-50% in MI HF vs 10-20% in SHAM; p<0.05); exercise training partly corrected this (20-30%; p<0.05 vs MI HF). In conclusion, exercise training partly reversed cardiomyocyte Ca2+ handling abnormalities observed during increasing twitch-stimulation frequencies in post-MI HF. This suggests a mechanism for improving reserve capacity and reducing arrhythmia susceptibility.