DESTABILIZATION OF RESPIRATORY MOTOR OUTPUT DURING SLEEP--CAUSES & CONSEQUENCES

我们将确定导致呼吸不稳定和 睡眠中的中枢性呼吸暂停及其对上呼吸道阻力的影响 使用慢性器械、未麻醉的狗和人类受试者。 1.中枢神经系统缺氧如何影响中枢神经系统损伤的程度和程度 清醒和睡眠时呼吸模式的稳定性？我们有 开发了一种独特的制剂，用于清醒和睡眠中的狗 因此颈动脉化学感受器的灌流独立于 全身循环和中枢神经系统循环。 2.是什么机制导致了呼吸机不稳定和中枢 睡眠时呼吸机输出受到干扰而导致的呼吸暂停？我们 将研究兴奋性短时程增强的相反作用 对比a)低碳酸血症，b)迷走神经反馈的抑制效应 肺和上呼吸道负压和c)控制系统“惯性”。 3.颈动脉化学感受器低碳酸血症本身的作用是什么 呼吸马达的输出和定时？使用分离的颈动脉 化学感受器的灌流，我们将测试稳态和 清醒状态下低碳酸血症对呼吸运动输出的一过性变化 还有沉睡的狗。 4.我们将使用被动和主动诱导的高呼吸系统来确定 一过性呼吸运动输出变化对中枢性呼吸暂停的影响 上呼吸道通畅性和阻力的研究 对呼吸道闭合的敏感度。 人类的睡眠通常具有明显和频繁的特点 呼吸机排气量和呼吸动力的波动，这对 对睡眠引起的气体交换、睡眠问题的严重影响 状态稳定和上呼吸道通畅。我们相信我们的提议 利用生理学中常见的扰动进行研究 准备工作提供了一种现实而全面的方法 睡眠障碍的复杂机制研究 呼吸和中枢性呼吸暂停。

We will determine the mechanisms which cause breathing instability and central apnea during sleep and their effects on upper airway resistance, using chronically instrumented, unanesthetized dogs and human subjects. 1. How does central nervous system hypoxia affect the magnitude and stability of breathing pattern during wakefulness and sleep? We have developed a unique preparation for use in waking and sleeping dogs whereby the carotid chemoreceptor is perfused independently of the systemic and CNS circulations. 2. What mechanisms contribute to ventilatory instability and central apnea following perturbations in ventilatory output during sleep? We will examine the opposing effects of excitatory short-term potentiation vs the inhibitory effects of a) hypocapnia, b) vagal feedback from the lung and upper airway negative pressure and c) control system "inertia". 3. What is the role of carotid chemoreceptor hypocapnia, per se on respiratory motor output and timing? Using the isolated carotid chemoreceptor perfusion, we will test the role of steady-state and transient changes in hypocapnia on respiratory motor output in the awake and sleeping dog. 4. We will use passive and actively-induced hyperneas to determine the affect of transient changes in respiratory motor output and central apnea on upper airway patency and resistance in humans who represent a wide spectrum of susceptibility to airway closure. Sleep in humans is often characterized by marked and frequent fluctuations in ventilatory output and the drive to breathe, which has serious implications for sleep induced problems in gas exchange, sleep state stability and upper airway patency. We believe our proposed studies using commonly encountered perturbations in physiologic preparations provide a realistic and comprehensive approach to investigation of the complex mechanisms underlying sleep-disordered breathing and central apnea.