SCOR IN CARDIOPULMONARY DISORDERS OF SLEEP

该计划代表了一个更新的申请是一个特殊的中心， 睡眠中的心脏病研究。的重要目标 SCOR的基础科学研究是建立神经机制 导致睡眠时上呼吸道张力减退。我们认为 治疗睡眠呼吸暂停的药物疗法 来阐明这些基本机制。这些神经生物学 调查涉及使用电生理学的补充研究 技术（项目2）、神经解剖学方法（项目1）和研究 在慢性，正常睡眠的动物（项目4）。这些研究首先 解决（项目2）的总体假设，即障碍是 上呼吸道运动活动减少的主要机制 睡吧注意力集中在脑干的胺能系统。 将进行研究，以审查不同相关部门的作用， 神经传递素这类研究将注意力引向复杂的神经系统 例如尾中缝。在项目1中，神经化学和 该系统的神经解剖学组织将使用 多种技术--束追踪，双标记， 免疫组织化学和受体放射自显影。REM睡眠中的呼吸暂停 与这种状态的阶段性事件有关。在项目4中，我们 提出脑桥喙部的一个区域，脑桥脚被盖 核（PPT），介导这些阶段性的呼吸现象和一系列的 研究阐明测试这一假设。这些基本的调查 导致了睡眠呼吸暂停动物模型的研究， （项目3），其中我们将研究神经肌肉适应 存在慢性阻塞性上呼吸道。该项目基于 上呼吸道阻塞导致适应性增加 上呼吸道扩张肌在清醒状态下的活动， 气道阻塞，导致肌肉继发性变化 自己作为项目3中正在进行的研究的一部分， 将使用我们开创的成像技术。CPAP的有效性 将在项目5中讨论，但这里的重点是模式 对白天嗜睡的影响。我们之前的研究发现 担心许多接受CPAP治疗的患者的功能处于次优状态 程度.这里提出的研究结果可能会有一个 对睡眠呼吸暂停患者的管理产生重大影响。因此，这是一个 综合计划，包括基本的神经生物学和 临床研究

This Program represents a renewal application to be a Special Center of Research for Cardiopulmonary Disorders in Sleep. An important goal of the basic science studies of the SCOR is to establish the neural mechanisms that lead to hypotonia of the upper airway during sleep. It is our view that pharmacological therapies for sleep apnea are most likely to come from elucidating these basic mechanisms. These neurobiological investigations involve complementary studies using electrophysiological techniques (Project 2), neuroanatomical approaches (Project 1),and studies in chronic, normally sleeping animals (Project 4). These studies are first addressing (Project 2) the overall hypothesis that disfacilitation is the major mechanism for reduction in motor activity in the upper airway during sleep. Attention is directed at the aminergic systems in the brainstem. Studies will be done to examine the role of the different relevant neurotransmitters. Such studies direct attention to complex neural systems such as the caudal raphe. In Project 1, the neurochemical and neuroanatomical organization of this system will be studied using a variety of techniques-tract tracing, double-labeling, immunohistochemistry, and receptor autoradiography. Apneas in REM sleep are associated with the phasic events of this state. In Project 4, we propose that an area in the rostral pons, the pedunculopontine tegmental nucleus (PPT), mediates these phasic respiratory phenomena and a series of studies are elucidated to test this postulate. These basic investigations lead to studies in the animal model of sleep apnea that we identified (Project 3), in which we will study neuromuscular adaptations to the presence of a chronically obstructed upper airway. This project is based on the premise that upper airway obstruction leads to an adaptive increase in activity of upper airway dilator muscles in wakefulness that prevents airway obstruction and results in secondary changes in the muscles themselves. As part of the studies being conducted in Project 3, novel imaging techniques, that we have pioneered, will be used. Efficacy of CPAP will be addressed in Project 5, but here the emphasis will be on patterns of use and impact on daytime sleepiness. Our previous studies have raised concerns that many patients prescribed CPAP are functioning at sub-optimal levels. The results of the studies proposed here are likely to have a major impact on how sleep apnea patients are managed. Thus, this is a comprehensive program incorporating both basic neurobiological and clinical research.