Laboratory of Experimental Cardiology, University of Leuven, KUL, Campus Gasthuisberg O/N 7th floor, Herestraat 49, B-3000 Leuven, Belgium.
Cardiovasc Res. 2010 Apr 1;86(1):72-81. doi: 10.1093/cvr/cvp381. Epub 2009 Dec 9.
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+) 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.
心肌梗死（MI）后早期运动可改善心肌功能和肌丝对 Ca(2+)的反应性。我们研究了这是否代表细胞重构的部分或完全逆转。
结扎左冠状动脉后，MI 小鼠可自由使用跑步轮（MI(EXE)，N = 22）或久坐（MI(SED)，N = 18）8 周，并与久坐假手术动物（SHAM，N = 11）进行比较。酶解分离非梗死左心室的心肌细胞。MI 中的心肌细胞明显更长，运动后更长（MI(EXE)为 165 +/- 3 µm，MI(SED)为 148 +/- 3 µm，SHAM 为 136 +/- 2 µm；P < 0.05，平均值 +/- SEM）；细胞宽度无差异。在 1、2 和 4 Hz 时用电场刺激测量收缩。MI(SED)中的空载细胞缩短明显降低（在 1 Hz 时，L/L(0)=4.4 +/- 0.3%，与 SHAM 的 6.7 +/- 0.4%相比；P < 0.05，在 2 和 4 Hz 时也是如此）。运动将细胞缩短恢复到 SHAM 值（MI(EXE)，L/L(0)=6.4 +/- 0.5%）。通过全细胞膜片钳测量膜电流和 Ca(2+)，用 Fluo-3 作为 Ca(2+)指示剂，均在 30°C 下进行。三组间 Ca(2+)瞬变幅度、I(CaL)和肌浆网 Ca(2+)含量无差异。仅在 MI(SED)中，4 Hz 时的舒张 Ca(2+)水平显着升高，自发 Ca(2+)释放事件（火花）呈增加趋势。MI 后动作电位时程延长，瞬时外向 K(+)电流明显减少；运动对其无影响。
MI 后早期进行自愿运动训练可使细胞收缩恢复正常，主要是由于肌丝对 Ca(2+)的反应性发生变化，并对舒张期 Ca(2+)处理有有益影响。然而，这种有益作用并不是重构的完全逆转，因为肥大和复极化 K(+)电流的丧失不受影响。
