AUTONOMIC MECHANISMS IN NEURALLY MEDIATED SYNCOPE

这项研究的目的是剖析自主神经系统 神经介导性晕厥的机制，对患者进行分类， 解开治疗的原理 对于自主神经反应知之甚少 神经介导性晕厥患者的头高位倾斜。第一 该补助金的主要目的是评估神经系统疾病患者- 介导的晕厥、静息自主神经功能和 自主神经系统头向上倾斜使用RR变异性和 压力反射敏感性这项研究将检验以下假设： 神经介导性晕厥的患者会有过度的自主神经 对头高位倾斜的反应（具有更大的迷走神经退缩和交感神经收缩） 兴奋），这与过度静脉汇集有关。我们计划 开发和测试一种新技术， 确定在头向上倾斜期间小腿体积的变化。测量 静脉汇集将与自主反应性相关， 神经介导的自主神经病理生理学的综合分析 晕厥。这将允许澄清的相对重要性， 启动刺激（过度静脉汇集）与不适当的 自主反应头向上倾斜（夸张的迷走神经撤回）在 这种疾病的发病机制。 这项资助的第二个主要目的是评估自主神经效应 神经介导性晕厥患者的两种治疗方法： 作用于交感神经系统和副交感神经系统的药物 这些药物的自主效应将使用RR变异性， 压力反射敏感性以及对阿托品的心率反应。的 这些药物对直立倾斜自主反应的影响将是 评价并与这些药物与静脉 合伙我们期望， 自主机制在神经系统疾病的发生和治疗中起作用， 介导的晕厥，将提供一个更合理和有效的方法， 治疗将在随机化安慰剂中进行治疗评价- 这些药物的对照试验将允许初步评估 这些药物的相对疗效（与安慰剂相比）， 防止倾斜试验诱发晕厥的能力。 随机化后， 倾斜床研究序列（安慰剂和药物），所有患者将 接受药物治疗并随访一年，无论结果如何 药物倾斜试验的结果这将有助于评估 药物治疗倾斜试验预测长期 功效 这项研究将在晕厥中心进行， 欧文临床研究中心的自主神经功能实验室 Research.在此CIDA期间，我将接受静脉测量培训 体积描记法和直接交感神经记录。广泛 生物统计学、实验设计和操作培训 临床试验将在比格博士的研究部门进行。

The research in this grant is designed to dissect out the autonomic mechanisms of neurally-mediated syncope, to classify patients, and to unravel how treatments work. Little is known about the autonomic response to head-up tilt in patients with neurally-mediated syncope. The first primary aim of this grant is to evaluate in patients with neurally- mediated syncope, resting autonomic function and the reflex response of the autonomic nervous system to head-up tilt using RR variability and baroreflex sensitivity. This research will test the hypothesis that patients with neurally-mediated syncope will have an exaggerated autonomic response to head-up tilt (with greater vagal withdrawal and sympathetic excitation) that is related to excessive venous pooling. We plan to develop and test a new technique which uses strain-gauge technology to determine changes in calf volume during head-up tilt. Measurements of venous pooling will be related to autonomic responsiveness providing an integrated analysis of the autonomic pathophysiology of neurally-mediated syncope. This will permit clarification of the relative importance of an initiating stimulus (excessive venous pooling) versus an inappropriate autonomic response to head-up tilt (exaggerated vagal withdrawal) in the pathogenesis of this disorder. The second primary aim of this grant is to evaluate the autonomic effects of two types of treatments for patients with neurally-mediated syncope: drugs which act on the sympathetic and parasympathetic nervous systems The autonomic effects of these drugs will be made using RR variability, baroreflex sensitivity, and the heart rate response to atropine. The effects of these drugs on the autonomic response to head-up tilt will be evaluated and related to the interaction of these drugs with venous pooling. We expect that integration of a better understanding of the autonomic mechanisms operative in the genesis and treatment of neurally- mediated syncope, will provide a more logical and effective approach to treatment. The evaluation of therapy will be made in randomized placebo- controlled trials of these drugs which will permit an initial assessment of the relative efficacy of these drugs (compared with placebo) in their ability to prevent tilt table induced syncope. After the randomized sequence of tilt table studies (placebo and drug), all patients will be treated with a drug and followed for one year, irrespective of the results of the tilt table study on the drug. This will allow an assessment of the ability of tilt table testing on drug therapy to predict long-term efficacy. This research will take place within the Syncope Center and a newly furnished Autonomic Function Laboratory in the Irving Center for Clinical Research. During this CIDA, I will be trained in the measurement of venous plethysmography and direct sympathetic nerve recordings. Extensive training in biostatistics, experimental design and the operation of clinical trials will take place within Dr. Bigger's Research Unit.