Exercise After Myocardial Infarction Improves Contractility and Decreases Myofilament Ca 2+ Sensitivity

Abstract

See related article, pages 1079–1088 While myocardial infarction (MI) is the major cause of heart failure, there are conflicting data over the roles of abnormal calcium handling and myofilament function. The acute injury leads to the activation of neurohormones and cytokines, subsequent myocardial remodelling, further decline in heart function, and finally overt heart failure. Depressed myocyte contractility in the remodelled myocardium can largely be explained by Ca2+ handling abnormalities.1 Abnormalities in myofilament function are less well understood. A seminal study in pigs demonstrated that impaired pump function three weeks after MI can also be attributed to decreased maximal isometric tension in skinned cardiomyocytes in areas remote from the ischemic border zone.2 Somewhat paradoxically, the impairment occurred in the context of increased Ca2+ sensitivity of the myofilaments. The authors attributed the increased Ca2+ sensitivity following MI to reduced protein kinase A-mediated troponin I (TnI) phosphorylation.2 Increased myofilament Ca2+ sensitivity has also been reported for end-stage human heart failure, apparently largely because of a reduction of TnI phosphorylation.3 One of the most effective and least expensive therapies for cardiovascular disease is exercise. Clinical studies generally show a benefit of exercise training and a reduction of cardiac mortality after MI by 26%.4 The question remains of how soon to start exercising, especially after a large MI. In several clinical5 and animal6,7 studies, there were detrimental consequences when exercise began immediately after an MI. In the current issue of Circulation Research , de Waard et al8 present remarkable data addressing the question of exercise training early post MI. After a large MI, mice were subjected to 8 weeks of “voluntary” exercise training. Exercise had no detrimental effects on mortality and minimal effects on myocardial hypertrophy and left ventricular remodelling. Furthermore, there …