CARDIAC DYSFUNCTION & SUDDEN DEATH MODIFIED BY EXERCISE

现在有越来越多的临床证据表明， 左心功能不全与心脏性猝死的关系 在从心肌梗塞中恢复的患者中。其作用机制 这种联系背后的原因仍有待确定。内部更改 自主神经系统可能是连接心脏的一个因素。 功能导致死亡率增加。因为心功能不全会 倾向于减少每搏量，交感神经增加和/或减少 副交感神经活动可能通过以下方式补偿心搏量的下降 增加心率和/或变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 更新期，事实上，众所周知，这会增加 室颤(VF)。在初步实验中，它已经被 有可能开发出一种动物模型，在该模型中VF可以可靠地和 可重复地诱导的。该模型结合了前壁心肌 运动中伴有心肌缺血的心肌梗死及停药。 在接受测试的动物中，大约有60%-70%发生了室颤。使用这个 模型，这一系列拟议的实验的目的是 调查：a)心功能和心功能的关系 对室颤的敏感性，以及b)自主神经的作用 从系统到猝死。此外，如果假设将脑室 对猝死的功能是正确的，然后是改善的干预 心功能应可减少猝死的发生率。这 假设将使用两种方法进行检验：耐力训练 训练和强心药物治疗。脑室不同之处 函数在静止时可能是微妙的，但当 心脏承受着压力。次极量运动，后负荷和 静息状态下的心肌缺血将被用作生理学相关 压力源。心功能的评估将使用区域和 全球心脏收缩功能指数。具体地说，细分 长度收缩性、每搏输出量和收缩期室壁 将调查压力-体积关系。舒张期特性 也将对心脏进行调查。以类似的方式，自主的 活动将使用药理学干预措施进行间接评估。

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.