The Effect of Exercise Training on Ca2+ Wave Probability After Myocardial Infarction Depends on Cardiac Function at Onset of Training.

Abstract

<h3>Background</h3> Altered Ca²⁺ handling in cardiomyocytes contributes to contractile dysfunction and increased risk of arrhythmias in heart failure. Exercise training (ET) can improve Ca²⁺ handling, with potential positive effects on contractile performance and risk of arrhythmias. We hypothesized that the effect of ET on pathological Ca²⁺ handling associated with arrhythmias, depends on the cardiac function at onset of ET. <h3>Method and Results</h3> Myocardial infarction was induced in male Wistar rats by ligation of the left coronary artery. One week after induction of infarction, rats were stratified by echocardiographic parameters to a non-failing group (MI+) and a failing group (CHF). Rats from both groups were randomized into a five-week high-intensity exercise training group (ET) or a sedentary control group (SED). Each training session consisted of five 8 minutes intervals at 80-90% of the running speed at maximal oxygen uptake (VO_2max, ml/kg/min), interspersed with two-minute periods at 60% running speed. After ET, ET-CHF had 24% higher VO_2max compared to SED-CHF (57±3 vs. 44±2, p<0.05), while ET-MI+ had 27% higher VO_2max compared to SED-MI+ (64±5 vs. 47±2, p<0.05). Ca²⁺ wave probability and parameters of Ca²⁺ handling were analyzed by Two-Way ANOVA to give overall values at 1, 2 and 4 Hz stimulation during ISO exposure. Overall Ca²⁺ wave frequency in isolated cardiomyocytes during a 10 seconds pause following field stimulation was reduced by 31% in ET-CHF compared to SED-CHF (69+6 vs. 100+6%, p<0.05). The overall Ca²⁺ reuptake rate in ET-CHF decreased by 16% compared to SED-CHF (84±3 vs. 100±3%, p<0.05). Ca²⁺ transient amplitude was 17% lower in the ET-CHF compared to SED-CHF (p<0.05), with no difference in SR Ca²⁺ content. Interestingly, the opposite effect on Ca²⁺ wave frequency was observed in ET-MI+ rats: Overall Ca²⁺ wave frequency was 35% higher in ET-MI+ compared to SED-MI+ (135+9 vs. 100+8%, p<0.05). Ca²⁺ reuptake rate in ET-MI+ was 7% lower than SED-MI+ (p<0.05), without differences in SR Ca²⁺ content or Ca²⁺ transient amplitude. <h3>Conclusion</h3> ET had opposite effects on Ca²⁺ wave probability in CHF and MI+ rats. These findings indicate that the effect of ET on Ca²⁺ handling after myocardial infarction could depend on the cardiac function at onset of ET.