Central and Peripheral Mechanisms of Sleep Apnea

睡眠呼吸暂停的中枢和外周机制

• 批准号: 7036612
• 负责人: CURTIS A SMITH
• 金额: $ 28.42万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036612
• 关键词: afferent nerve; baroreceptors; blood pressure; carbon dioxide; carotid body; cerebral ischemia /hypoxia; chemoreceptors; clinical research; dogs; human subject; hypercapnia; hyperpnea; innervation; isolation perfusion; patient oriented research; pulmonary hypertension; pulmonary respiration; respiratory hypoxia; sleep apnea; sympathetic nervous system

DESCRIPTION (provided by applicant): Based on our recent findings in sleeping humans and dogs we propose that the ventilatory responsiveness to CO2 below eupnea is highly labile depending on the type and direction of prevailing ventilatory drive and is a critical determinant of many types of breathing instability and apnea. We propose five major aims to study causes and consequences of a labile apneic threshold on the CO2 reserve (i.e., PETCO2 EUPNEA -- PETCO2APNEA ; an index of propensity for ventilatory instability). First, we will use the sleeping dog model and our pressure support ventilation (PSV) method to determine the CO2 reserve and change in the susceptibility to apnea caused by raised left atrial pressure, as occurs in congestive heart failure. Aims 2 & 3 will utilize our intact sleeping dog preparation in which the carotid chemoreceptor is isolated and perfused via extracorporeal circulation. We will determine the sensitivities of the central vs. peripheral chemoreceptors to transient reductions in PaCO2 and their relative contributions to the genesis of apnea. Our capability for isolating central from peripheral chemoreceptors in the intact sleeping animal will also be used to determine the relative importance of peripheral chemoreceptor hypoxia vs. CNS hypoxia in determining CO2 reserve and the propensity for ventilatory instability. In Aim 4, we will use sleeping humans to study the causes and consequences to ventilatory stability of the dynamic changes in cerebral blood flow which accompany periodic breathing during sleep in hypoxia. Finally, we will test the hypothesis that obstructive sleep apnea patients have a propensity for unstable respiratory motor output and a sensitive apneic threshold (i.e., narrowed CO2 reserve) because of their chronic exposure to nocturnal hypoxemia. We will test this hypothesis further by exposing dogs to chronic intermittent hypoxia to determine if their propensity for ventilatory instability increases over the duration of chronic intermittent hypoxic exposure.

描述（由申请人提供）：基于我们最近在睡眠的人和狗中的发现，我们提出，根据主要呼吸驱动的类型和方向，在正常呼吸下对CO2的呼吸响应是高度不稳定的，并且是许多类型的呼吸不稳定和呼吸暂停的关键决定因素。我们提出了五个主要目标来研究不稳定的呼吸暂停阈值对CO2储备的原因和后果（即，PETCO2 Eupnea --PETCO 2呼吸暂停;呼吸不稳定倾向指数）。首先，我们将使用睡眠狗模型和我们的压力支持通气（PSV）方法来确定CO2储备和左心房压力升高引起的呼吸暂停的易感性变化，如充血性心力衰竭。目的2和3将利用我们的完整的睡眠狗准备，其中颈动脉化学感受器被分离并通过体外循环灌注。我们将确定中枢与外周化学感受器对PaCO 2瞬时降低的敏感性及其对呼吸暂停发生的相对贡献。我们在完整睡眠动物中从外周化学感受器分离中枢的能力也将用于确定外周化学感受器缺氧与CNS缺氧在确定CO2储备和呼吸不稳定性倾向中的相对重要性。在目标4中，我们将使用睡眠的人来研究缺氧睡眠期间伴随周期性呼吸的脑血流动态变化对睡眠稳定性的原因和后果。最后，我们将检验阻塞性睡眠呼吸暂停患者具有不稳定的呼吸运动输出和敏感的呼吸暂停阈值（即，二氧化碳储备减少），因为他们长期暴露于夜间低氧血症。我们将通过将狗暴露于慢性间歇性缺氧来进一步测试这一假设，以确定它们的呼吸不稳定性的倾向是否随着慢性间歇性缺氧暴露的持续时间而增加。