AUTONOMIC MECHANISMS IN NEURALLY MEDIATED SYNCOPE

这项资助中的研究旨在剖析自主神经。 神经介导性晕厥的机制、患者分类和 揭示治疗是如何起作用的。人们对自主神经反应知之甚少。 神经介导性晕厥患者的直立倾斜。第一 这项拨款的主要目的是评估患有神经性- 介导性晕厥、静息自主神经功能和反射反应 使用RR变异性和RR的自主神经系统对头高位倾斜 压力反射敏感性。这项研究将检验这一假设 神经介导性晕厥的患者会有夸大的自主神经 对仰卧位的反应(有更大的迷走神经收缩和交感 兴奋性)，这与过度的静脉淤积有关。我们计划 开发和测试一项新技术，该技术使用应变计技术来 确定头高位倾斜时小腿体积的变化。测量 静脉汇集将与自主神经反应性相关，提供 神经介导的自主神经病理生理学的综合分析 晕厥。这将允许澄清一个 启动刺激(过度静脉回输)与不适当的 高位倾斜(夸大迷走神经退缩)的自主神经反应 这种疾病的发病机制。 这项拨款的第二个主要目的是评估自主神经的影响。 神经介导性晕厥患者的两种治疗方法： 作用于交感和副交感神经系统的药物 这些药物的自主神经效应将使用RR变异性， 压力感受性反射敏感性和心率对阿托品的反应。这个 这些药物对头高位倾斜的自主神经反应的影响将是 评价这些药物与静脉的相互作用并与之相关 拼车。我们期待着更好地理解 自主神经机制在神经性疾病的发生和治疗中的作用 介导性晕厥，将提供一种更符合逻辑和更有效的方法 治疗。治疗评估将在随机安慰剂中进行- 这些药物的对照试验将允许进行初步评估 这些药物的相对疗效(与安慰剂相比) 预防倾斜床引起晕厥的能力。在随机化之后 倾斜表研究序列(安慰剂和药物)，所有患者都将 用药物治疗，并随访一年，无论结果如何 关于药物的倾斜表研究。这将允许评估 倾斜试验对药物治疗远期疗效的预测能力 功效。 这项研究将在晕厥中心和一个新的 欧文临床中心配备的自主神经功能实验室 研究。在这次CIDA期间，我将接受静脉测量方面的培训 体积描记和直接的交感神经记录。广泛性 生物统计学、实验设计和操作方面的培训 临床试验将在比格博士的研究单位内进行。

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.