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

Abstract

Exercise started early after myocardial infarction (MI) improves in vivo cardiac function and myofilament responsiveness to Ca(2+). We investigated whether this represents partial or complete reversal of cellular remodelling. Mice with MI following left coronary ligation were given free access to a running wheel (MI(EXE), N = 22) or housed sedentary (MI(SED), 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 microm in MI(EXE) vs. 148 +/- 3 microm in MI(SED) and 136 +/- 2 microm 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 MI(SED) (at 1 Hz, L/L(0)=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 (MI(EXE), L/L(0)=6.4 +/- 0.5%). Membrane currents and [Ca(2+)](i) were measured via whole-cell patch clamping, with Fluo-3 as Ca(2+) indicator, all at 30 degrees C. Ca(2+) transient amplitude, I(CaL) and sarcoplasmic reticulum Ca(2+) content were not different between the three groups. Diastolic Ca(2+) levels at 4 Hz were significantly elevated in MI(SED) only, with a trend to increased spontaneous Ca(2+) release events (sparks). Action potential duration was increased and transient outward K(+) currents significantly reduced after MI; this was unaffected by exercise. Early voluntary exercise training after MI restores cell contraction to normal values predominantly because of changes in the myofilament Ca(2+) response and has a beneficial effect on diastolic Ca(2+) handling. However, the beneficial effect is not a complete reversal of remodelling as hypertrophy and loss of repolarizing K(+) currents are not affected.