Alcohol and Neurovascular Control in Humans

项目摘要 人们普遍认识到，酗酒与心血管疾病增加有关 风险很大，但其中很大一部分是基于流行病学研究，机制仍然知之甚少。 交感神经过度活动被认为是酒精介导的心血管疾病的一种潜在机制 疾病，但缺乏直接证据。建议的计划是我们迈向长远目标的第一步- 学期目标是探讨酒精引起的高血压、中风和心脏性猝死，并具有实用性 可能会减少这些心血管疾病发生率的干预措施。拟议的项目重点是 晚间饮酒对夜间和清晨自主神经功能的影响 男性和女性酗酒者的反应性。在目标1中，将确定晚上饮酒的影响 关于夜间自主神经控制和第二天早上的交感神经反应。目标2将 确定性别(男性与女性)和卵巢周期(卵泡早期与黄体中期)对 人类对晚间酒精的交感神经反应。目标3将决定是否持续积极 在夜间和清晨，呼吸道压力(CPAP)可钝化酒精介导的交感神经兴奋。一个 探索性目的将确定对酒精和CPAP的自主反应是否与情感状态有关 和精神运动表现。我们的中心假设是晚上饮酒会导致 晚上和第二天早上交感神经过度活跃，这种交感神经兴奋将是 在CPAP治疗后增加妇女和钝化。这个项目的新颖性和创新性在于我们的 机械性目标通过干预目标得到支持，其中包括随机对照试验(CPAP与 假CPAP)。该项目使用公认的黄金标准方法来评估睡眠(多导睡眠图) 交感神经活性和反应性(显微神经学)。总而言之，这个项目将决定 模拟“狂欢”饮酒对兴奋时神经心血管功能的影响 男性和女性酗酒者的心血管风险(即睡眠和清晨)，并测试潜在的 钝化酒精所致自主神经功能障碍的治疗策略(即CPAP)。

Project Summary There is wide-spread recognition that ‘binge’ alcohol consumption is associated with increased cardiovascular risk, but much of this is based on epidemiological studies and mechanisms remain poorly understood. Sympathetic overactivity has been suggested as a potential mechanism for alcohol-mediated cardiovascular disease, but direct evidence is lacking. The proposed project represents our first step in the pursuit of a long- term goal to explore alcohol-mediated hypertension, stroke, and sudden cardiac death, and practical interventions that might reduce the incidence of these cardiovascular conditions. The proposed project focuses on the impact of evening alcohol consumption on nocturnal and early morning autonomic function and reactivity in male and female binge drinkers. In aim 1, will determine the effect of evening alcohol consumption on nocturnal autonomic control and sympathetic neural responsiveness the subsequent morning. Aim 2 will determine the influence of sex (male vs. female) and the ovarian cycle (early follicular vs. midluteal phase) on sympathetic neural responsiveness to evening alcohol in humans. Aim 3 will determine if continuous positive airway pressure (CPAP) blunts alcohol-mediated sympathoexcitation at night and early morning. An exploratory aim will determine if autonomic responses to alcohol and CPAP are associated with affective states and psychomotor performance. Our central hypothesis is that evening alcohol consumption will elicit sympathetic overactivity at night and the subsequent morning, and that this sympathoexcitation will be augmented women and blunted after CPAP treatment. The novelty and innovation of this project is that our mechanistic aims are bolstered with an interventional aim that includes a randomized, control trial (CPAP vs. sham-CPAP). The project utilizes established, gold-standard methods for assessing sleep (polysomnography) and sympathetic neural activity and reactivity (microneurography). In summary, this project will determine the impact of simulated ‘binge’ alcohol consumption on neural cardiovascular function at times of elevated cardiovascular risk (i.e., sleep and early morning) in male and female binge drinkers, and test a potential therapeutic strategy (i.e., CPAP) to blunt alcohol-induced autonomic dysfunction.