Aït Mou Younss, Reboul Cyril, Andre Lucas, Lacampagne Alain, Cazorla Olivier
INSERM U637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, Montpellier, France.
Cardiovasc Res. 2009 Feb 15;81(3):555-64. doi: 10.1093/cvr/cvn229. Epub 2008 Aug 14.
The exercise-induced beneficial mechanisms after long-term myocardial infarction (MI) are incompletely understood. The present study evaluated the effect of treadmill exercise training (5 weeks), started at a late stage of heart failure (HF) (13 weeks post-MI), on rat left ventricle remodelling and dysfunction of the regional global and cellular contractile functions.
In vivo echocardiography confirmed that sub-endocardial (ENDO) layers contract more (+86%) and faster (+50%) than the sub-epicardial (EPI) layers. This gradient was lost in MI rats due to a predominant reduction in the ENDO layer contractility. Exercise partially restored the amplitude and velocity of ENDO contraction, resulting in a partial recovery of the pump function indexed by the aortic blood-flow velocity time integral. At the cellular level, MI impaired ENDO contractile properties by reducing cell shortening (10-7%), calcium transient, and myofilament Ca(2+) sensitivity. These alterations were normalized by exercise. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA)2a expression and myosin light chain (MLC)-2 phosphorylation in ENDO cells were significantly reduced after MI and were restored by exercise. The EPI layer was only slightly reduced in vivo without cellular alterations.
This study shows that exercise performed at a late stage after MI restored a transmural non-uniformity of myocardium lost during HF. Recoveries of Ca(2+) homeostasis and myofilament function of cardiomyocytes contribute to this beneficial effect.
长期心肌梗死（MI）后运动诱导的有益机制尚未完全明确。本研究评估了在心力衰竭（HF）晚期（MI后13周）开始的跑步机运动训练（5周）对大鼠左心室重构以及局部、整体和细胞收缩功能障碍的影响。
体内超声心动图证实，心内膜下层（ENDO）的收缩幅度（增加86%）和速度（增加50%）均高于心外膜下层（EPI）。由于ENDO层收缩力显著降低，MI大鼠中这种梯度消失。运动部分恢复了ENDO收缩的幅度和速度，导致以主动脉血流速度时间积分表示的泵功能部分恢复。在细胞水平上，MI通过减少细胞缩短（10 - 7%）、钙瞬变和肌丝Ca(2+)敏感性来损害ENDO的收缩特性。这些改变通过运动得以正常化。MI后ENDO细胞中的肌浆网Ca(2+)-ATP酶（SERCA）2a表达和肌球蛋白轻链（MLC）-2磷酸化显著降低，并通过运动得以恢复。EPI层在体内仅略有降低，无细胞改变。
本研究表明，MI后晚期进行的运动恢复了HF期间丧失的心肌跨壁不均匀性。心肌细胞Ca(2+)稳态和肌丝功能的恢复有助于这种有益效果。
