AUTONOMIC MODULATION OF ISCHEMIC ARRHYTHMIAS

许多临床和动物研究表明，自主神经与 系统在某些心律失常的发生中起作用 心源性猝死，几乎占所有事件的25% 我们研究的长期目标是美国每年的死亡人数 是研究自主神经的作用机制(S) 系统调节心脏的兴奋性特性，进而 受缺血/梗死的调节，促进、沉淀或 预防冠脉术后心律失常的发生 遮挡。尽管人们对生理和心理方面的了解很多 刺激自主神经受体的生化后果，以及 事实上，已经克隆了几个受体，整合了数据 并将细胞和亚细胞研究的结果与 心律失常在体内和体内动物模型中的发展 心律失常的患者是缺乏的。我们计划推出一系列 的研究都是基于这样一种假设 脑梗塞和/或缺血改变神经轴突的功能 穿过缺血/梗死区，产生急性 (功能性)然后慢性(解剖学)去神经，去神经 超敏反应和神经再支配。这些自主神经的影响 调节心脏的兴奋性，导致抑制， 促进或引发心律失常。具体的 目的是调查负责功能的机制 急性心肌缺血后去神经，确定是否 缺血预适应改变随后的程度和时间 急性失神经的病程，判断传入的一致性 以及传出的缺血性去神经，决定了某些类型的 心肌梗死比其他心肌梗死更容易导致心律失常， 确定后去极化是否对某些 心律失常，确定是否暴露于奎尼丁和洋地黄 在交感神经丧失的心脏中更容易导致心律失常 超敏反应，确定肾上腺素能和 胆碱能超敏反应，并确定交感神经或 心肌梗死后患者出现迷走神经失神经 脑梗塞是导致心律失常的原因。自主神经刺激将是 由电刺激传出迷走神经和 交感神经，心肌传入反射的刺激 使用缓激肽和尼古丁，并输注各种药物。 使用间碘苯甲基胍进行无创成像将用于 患者传出心肌交感神经支配的测定 患有冠状动脉疾病。

Many clinical and animal studies implicate the autonomic nervous system in the genesis of some of the arrhythmias responsible for sudden cardiac death, an event that accounts for almost 25% of all deaths annually in the U.S. The long-term objective of our studies is to investigate the mechanism(s) by which the autonomic nervous system modulates cardiac excitable properties and is in turn modulated by the ischemia/infarction, to promote, precipitate or prevent the development of cardiac arrhythmias after coronary occlusion. Although much is known about the physiological and biochemical consequences of stimulating autonomic receptors, and indeed, several of the receptors have been cloned, data integrating and linking findings from cellular and subcellular research to the development of cardiac arrhythmias in animal models in vivo and in patients with cardiac arrhythmias are lacking. We plan a series of studies based on the overall hypothesis that the myocardial infarction and/or ischemia alters the function of nerve axons passing through the ischemic/infarcted area, producing acute (functional) and then chronic (anatomical) denervation, denervation supersensitivity and reinnervation. These autonomic influences modulate cardiac excitable properties, resulting in suppression, facilitation or initiation of cardiac arrhythmias. The specific aims are to investigate mechanisms responsible for the functional denervation following acute myocardial ischemia, determine whether preconditioning ischemia alters the subsequent degree and time course of acute denervation, determine the concordance of afferent and efferent ischemic denervation, determine whether some types of myocardial infarction are more arrhythmogenic than others, determine whether after depolarizations are responsible for some arrhythmias, determine whether exposure to quinidine and digitalis is more arrhythmogenic in hearts with sympathetic denervation and supersensitivity, determine the mechanisms of adrenergic and cholinergic supersensitivity and determine whether sympathetic or vagal denervation occurs in patients following myocardial infarction and is arrhythmogenic. Autonomic stimulation will be produced by electrical stimulation of efferent vagal and sympathetic nerves, provocation of afferent myocardial reflexes with bradykinin and nicotine and infusion of various drugs. Noninvasive imaging with metaiodobenzylguanidine will be done to determine efferent myocardial sympathetic innervation in patients with coronary artery disease.