AUTONOMIC MODULATION OF ISCHEMIC ARRHYTHMIAS

许多临床和动物研究表明， 系统在一些心律失常的起源负责 心源性猝死，这一事件几乎占所有死亡的25%， 我们研究的长期目标是 是研究自主神经系统 系统调节心脏可兴奋特性， 通过局部缺血/梗塞调节，以促进、沉淀或 预防冠心病后心律失常的发生 闭塞 尽管人们对生理和 刺激自主神经受体的生化后果，以及 事实上，一些受体已经被克隆，数据整合， 并将细胞和亚细胞研究的发现与 在动物模型中体内和体内心律失常的发展 缺乏心律失常患者。 我们计划一系列 研究的总体假设是， 梗塞和/或局部缺血改变神经轴突的功能 穿过缺血/梗塞区域，产生急性 （功能性）和慢性（解剖性）去神经支配， 超敏反应和神经再生 这些自主神经的影响 调节心脏可兴奋特性，导致抑制， 促进或引发心律失常。 具体 目的是调查负责职能的机制 急性心肌缺血后去神经支配，确定是否 预处理缺血改变了随后的程度和时间 急性去神经过程，确定传入神经的一致性， 和传出缺血性去神经支配，确定是否有些类型的 心肌梗死比其他心肌梗死更易发生， 确定去极化后是否负责一些 心律失常，确定是否暴露于奎尼丁和洋地黄 在交感神经失神经支配的心脏中更易致心律失常， 超敏反应，确定肾上腺素能和 胆碱能超敏反应，并确定是否交感神经或 迷走神经去神经发生在心肌梗死后的患者中， 梗塞和致血栓性。 自主神经刺激将是 由传出迷走神经的电刺激产生， 交感神经，传入心肌反射的激发 与缓激肽和尼古丁以及输注各种药物一起使用。 将使用间碘苄胍进行非侵入性成像， 确定患者的传出心肌交感神经支配 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.