CARDIAC DYSFUNCTION & SUDDEN DEATH MODIFIED BY EXERCISE

现在有越来越多的临床证据表明， 心源性猝死与左心室功能不全的关系 在心肌梗死恢复期的患者中。 的机制 这种联系的根本原因尚待确定。 内部变更 自主神经系统可能代表了一个因素， 增加了死亡率。 因为心室功能障碍 倾向于减少每搏输出量，增加交感神经和/或减少 副交感神经活动可以通过以下方式补偿心搏量的下降 增加心率和/或正性肌力状态以维持更正常的 心输出量 这些自主活动的变化会减少 事实上，众所周知， 心室颤动（VF）。 在初步实验中， 有可能开发一种动物模型，其中VF可以可靠地 可重复诱导。 该模型结合了前壁心肌 运动中心肌缺血性梗死及其终止。 大约60-70%的动物发生VF。 使用此 模型，这一系列拟议实验的目的是 研究：a）心室功能与 对VF的易感性，和B）自主神经的贡献 系统突然死亡。 此外，如果假设心室 功能对猝死是正确的，然后干预，改善 心功能应降低猝死的发生率。 这 假设将使用两种方法进行测试：耐力运动 训练和强心药物治疗。 心室肌的差异 功能在静止时可能是微妙的，但在静止时可能会变得更加明显。 心脏有压力。 次极量运动，后负荷改变， 静息时的心肌缺血将被用作生理相关的 压力源 心室功能将使用局部和 心脏收缩功能的总体指数。 具体来说，段 长度收缩性、每搏输出量和收缩期心室 将研究压力-体积关系。 舒张性能 也将对心脏进行研究。 以类似的方式， 将使用药理学干预间接评估活性。

There is now a growing body of clinical evidence that suggests a strong association between left ventricular dysfunction and sudden cardiac death in patients recovering from myocardial infarction. The mechanisms underlying this association remain to be determined. Alterations within the autonomic nervous system may represent one factor that links cardiac function to an increased mortality. Since ventricular dysfunction would tend to reduce stroke volume, an increased sympathetic and/or decreased parasympathetic activity may compensate for this fall in stroke volume by increasing heart rate and/or inotropic state to maintain a more normal cardiac output. These changes in autonomic activity would decrease refactory period and are, in fact, known to increase the vulnerability to ventricular fibrillation (VF). During preliminary experiments, it has been possible to develop an animal model in which VF could be reliably and reproducibly induced. This model combined anterior wall myocardial infarction with myocardial ischemia during exercise and its cessation. Approximately 60-70% of the animals so tested developed VF. Using this model, it is the purpose of this series of proposed experiments to investigate: a) the relationship between ventricular function and susceptibility to VF, and b) the contribution of the autonomic nervous system to sudden death. Furthermore, if the hypothesis linking ventricular function to sudden death is correct, then interventions that improve cardiac function should reduce the incidence of sudden death. This hypothesis will be tested using two approaches: endurance exercise training and cardiotonic drug therapy. The differences in ventricular function are probably subtle at rest but may become more pronounced when the heart is stressed. Submaximal exercise, alterations in afterload and myocardial ischemia at rest will be used as physiological relevant stressors. Ventricular function will be assessed using both regional and global indices of cardiac contractile function. Specifically, segment length contractility, stroke volume, and systolic ventricular pressure-volume relationships will be investigated. Diastolic properties of the heart will also be investigated. In a similar manner, autonomic activity will be indirectly assessed using pharmacological interventions.