Background-Recent clinical studies suggest that endurance sports may promote cardiac arrhythmias. The aim of this study was to use an animal model to evaluate whether sustained intensive exercise training induces potentially adverse myocardial remodeling and thus creates a potential substrate for arrhythmias. Methods and Results-Male Wistar rats were conditioned to run vigorously for 4, 8, and 16 weeks; time-matched sedentary rats served as controls. Serial echocardiograms and in vivo electrophysiological studies at 16 weeks were obtained in both groups. After euthanasia, ventricular collagen deposition was quantified by histological and biochemical studies, and messenger RNA and protein expression of transforming growth factor-1, fibronectin-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I, and procollagen-III was evaluated in all 4 cardiac chambers. At 16 weeks, exercise rats developed eccentric hypertrophy and diastolic dysfunction, together with atrial dilation. In addition, collagen deposition in the right ventricle and messenger RNA and protein expression of fibrosis markers in both atria and right ventricle were significantly greater in exercise than in sedentary rats at 16 weeks. Ventricular tachycardia could be induced in 5 of 12 exercise rats (42%) and only 1 of 16 sedentary rats (6%; Pϭ0.05). The fibrotic changes caused by 16 weeks of intensive exercise were reversed after an 8-week exercise cessation.
Conclusions-In this animal model, we documented cardiac fibrosis after long-term intensive exercise training, togetherwith changes in ventricular function and increased arrhythmia inducibility. If our findings are confirmed in humans, the results would support the notion that long-term vigorous endurance exercise training may in some cases promote adverse remodeling and produce a substrate for cardiac arrhythmias. (Circulation. 2011;123:13-22.)Key Words: arrhythmia Ⅲ exercise Ⅲ fibrosis R egular physical activity confers benefits that are widely recognized such as improved cardiovascular risk profiles and prevention of coronary heart disease and diabetes mellitus. 1,2 Regular exercise also directly and positively affects cardiac physiology (eg, increased myocardial oxygen supply and enhanced myocardial contractility), both in the general population 3 and in patients with cardiovascular disease. 4
Editorial see p 5 Clinical Perspective on p 22Long-term exercise induces hemodynamic changes and alters the loading conditions of the heart, with specific effects depending on the type of sport and intensity, that are most evident among athletes. 5 Cardiac adaptations in highly trained subjects include increased left ventricular (LV) and right ventricular (RV) diameters, enlarged left atrial (LA) dimensions, and increased cardiac mass and LV wall thickness. 5,6 These changes, together with a preserved ejection fraction, have classically characterized the physiology of the "athlete's heart." 5 Despite the evident benefits of an active lifestyle, 1-4 numerous observation...
