SUDDEN CARDIAC DEATH--PREVENTION BY NEURAL MODULATION

主要的目标是评估非药理学的可能性 后来正常人自主神经系统的操作 改变了心源性猝死的风险。这是合乎逻辑的结果 认为心脏交感神经活性高是导致心律失常的 有利于室颤(VF)的发生；心脏高度迷走神经 急性心肌缺血期间的活动是抗纤颤的，可能是 救命之恩。这项研究将使用一种既定的慢性 研究人员建立了心脏性猝死的动物模型。 意识清醒的狗进行次极量运动负荷测试；在开始时 最后一分钟的锻炼，当心 心率210-220b/min，冠状动脉回旋支闭塞两分钟 动脉做了手术。闭塞一分钟后，运动停止一次 遮挡将额外保持一分钟。使用此协议，VF 40%的动物在很大程度上依赖自主神经反射 回应。在本研究中，运动训练将被用来诱导 心脏自主神经反射控制的具体变化，即 增强迷走神经的张力反射。压抑的压力反射敏感性(BRS)， 在很大程度上是迷走神经反射减弱的标志，与 即使在正常人身上也有猝死的风险。因此，首字母 将根据以下三个不同级别执行风险分层 BR(1，小于15；2，介于15和20之间；3，大于20 毫秒/毫米汞)，动物被随机分成两个处理组。一组 将接受为期六周的运动训练，而另一个将担任 凯奇让对照组休息了相当的一段时间。六周后， 猝死的风险将根据明显的 患有抑郁BRS的狗。运动训练对儿童心理健康的影响 心脏的电生理学特征及其易感性 室性心动过速将通过测定心室不应性和 重复性早搏的阈值。阿托品的自主神经阻断作用 和/或心得安，或由毒扁豆碱对羟甲喋呤的刺激， 将用于划分主要涉及 具体结果：室性心动过速与生存。将会有明显和重大的健康 健康个体的运动训练应减少相关影响 在缺血事件中发生心源性猝死的风险。

The primary objective is to evaluate the possibility that non-pharmacologic manipulation of the autonomic nervous system in normal individuals later modifies the risk for sudden cardiac death. This is a logical consequence of the concept that high cardiac sympathetic activity is arrhythmogenic and favors the onset of ventricular fibrillation (VF); high cardiac vagal activity during acute myocardial ischemia is antifibrillatory and may be life-saving. The study will be performed using an established chronic animal model for sudden cardiac death developed by the investigators. Conscious dogs perform a sub-maximal exercise stress test; at the beginning of the last minute of exercise, when heart rate os 210-220 b/min, a two minute occlusion of the circumflex coronary artery is performed. After on e minute of occlusion, exercise stops an occlusion is maintained for an additional minute. With this protocol, VF occurs in 40% of the animals being largely dependent on autonomic reflex responses. In the present study, exercise training will be used to induce specific changes in the autonomic reflex control of the heart, i.e. to augment vagal tone reflexes. A depressed baroreflex sensitivity (BRS), largely a marker of weak vagal reflexes, is associated with an increased risk for sudden death even in normal individuals. Accordingly, an initial risk stratification will be performed based on three different levels of BRS (one, less that 15; two, between 15 and 20; and three, greater than 20 msec/mmHg) and the animals randomized into two treatment groups. One group will undergo exercise training for six weeks while the other serves as a cage rested control for an equivalent period of time. After six weeks, risk for sudden death will be added based on the outcome of the evident in dogs with depressed BRS. The effect of exercise training on the electrophysiologic characteristics of the heart and on its vulnerability to VF will be tested by determining ventricular refractoriness and the threshold for repetitive extrasystole. Autonomic blockade, by atropine and/or propranolol, or stimulation by the muscarinic against oxotremorine, will be used to partition the autonomic components largely involved in the specific outcome: VF vs survival. There would be obvious and major health related implications should exercise training in healthy individuals reduce the later risk for sudden cardiac death during an ischemia event.