Early exercise training after myocardial infarction prevents contractile but not electrical remodelling or hypertrophy

Aims: Exercise started early after myocardial infarction (MI) improves in vivo cardiac function and myofilament responsiveness to Ca2+. We investigated whether this represents partial or complete reversal of cellular remodelling. Methods and results: Mice with MI following left coronary ligation were given free access to a running wheel (MIEXE, N = 22) or housed sedentary (MISED, N = 18) for 8 weeks and compared with sedentary sham-operated animals (SHAM, N = 11). Myocytes were enzymatically isolated from the non-infarcted left ventricle. Myocytes in MI were significantly longer and even more so with exercise (165 ± 3 μm in MIEXEvs. 148 ± 3 μm in MISEDand 136 ± 2 μm in SHAM; P < 0.05, mean ± SEM); cell width was not different. Contraction was measured during electrical field stimulation at 1, 2, and 4 Hz. Unloaded cell shortening was significantly reduced in MISED(at 1 Hz, L/L0=4.4 ± 0.3% vs. 6.7 ± 0.4% in SHAM; P < 0.05, also at 2 and 4 Hz). Exercise restored cell shortening to SHAM values (MIEXE, L/L0=6.4 ± 0.5%). Membrane currents and [Ca2+]iwere measured via whole-cell patch clamping, with Fluo-3 as Ca2+indicator, all at 30°C. Ca2+transient amplitude, ICaLand sarcoplasmic reticulum Ca2+content were not different between the three groups. Diastolic Ca2+levels at 4 Hz were significantly elevated in MISEDonly, with a trend to increased spontaneous Ca2+release events (sparks). Action potential duration was increased and transient outward K+currents significantly reduced after MI; this was unaffected by exercise. Conclusions: Early voluntary exercise training after MI restores cell contraction to normal values predominantly because of changes in the myofilament Ca2+response and has a beneficial effect on diastolic Ca2+handling. However, the beneficial effect is not a complete reversal of remodelling as hypertrophy and loss of repolarizing K+currents are not affected.

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