Cardiac Arrhythmogenic Remodeling in a Rat Model of Long-Term Intensive Exercise Training
Cardiac Arrhythmogenic Remodeling in a Rat Model of Long-Term Intensive Exercise Training
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DOI：
10.1161/circulationaha.110.938282
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发表时间：
2011-01-04
期刊：
影响因子：
37.8
通讯作者：
Mont, Lluis
中科院分区：
文献类型：
--
作者：
Benito, Begona;Gay-Jordi, Gemma;Mont, Lluis
背景-最近的临床研究表明，耐力运动可能会促进心律失常。本研究的目的是使用动物模型，以评估是否持续的高强度运动训练诱导潜在的不利心肌重塑，从而创造了一个潜在的基板为arrhythmia.Methods和Results-Male Wistar大鼠进行了空调运行大力为4，8，和16周;时间匹配的久坐不动的大鼠作为对照。在两组中获得了16周时的系列超声心动图和体内电生理研究。安乐死后，通过组织学和生物化学研究定量心室胶原沉积，并在所有4个心腔中评价转化生长因子β 1、纤连蛋白1、基质金属蛋白酶2、金属蛋白酶组织抑制剂1、前胶原-I和前胶原-III的信使RNA和蛋白表达。在16周时，运动大鼠出现离心性肥大和舒张功能障碍，以及心房扩张。此外，16周时，运动时右心室胶原蛋白沉积以及心房和右心室纤维化标记物的信使RNA和蛋白质表达均显着高于久坐大鼠。12只运动大鼠中有5只（42%）可诱发室性心动过速，而16只安静大鼠中只有1只（6%; P = 0.05）可诱发室性心动过速。16周的高强度运动引起的纤维化的变化被逆转后，8周的exercise ceasing. Conclusions，在这个动物模型中，我们记录了心脏纤维化后，长期的高强度运动训练，以及心室功能的变化和增加心律失常inductives。如果我们的发现在人类中得到证实，结果将支持长期剧烈耐力运动训练在某些情况下可能促进不良重塑并产生心律失常的底物的观点。（循环。2011;123：13-22.）
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-beta 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%; P = 0.05). 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, together with 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.)