CAUSES OF SLEEP-INDUCED BREATHING INSTABILITIES

在睡眠期间，随着对泵和上气道呼吸肌的“觉醒”驱动的丧失，呼吸的控制变得高度依赖于来自化学感受器和机械感受器的反射反馈输入，并且容易受到来自化学感受器和机械感受器的反射反馈输入的影响。因此，睡眠引起的呼吸不稳定是常见的，并且即使在一般人群中也具有显著的患病率。睡眠揭示了一个高度敏感的低碳酸血症诱导的呼吸暂停阈值，但我们不知道这种机制在各种类型的睡眠呼吸障碍中起什么作用，因为我们不知道它的作用部位，在强大的背景影响下，如中枢神经系统缺氧，慢性低碳酸血症/高碳酸血症，改变睡眠状态或改变呼吸刺激（可能是睡眠特有的），它的敏感性变化。我们将使用睡眠中的人和狗，后者与额外的皮层灌注的分离颈动脉化学感受器，以量化的影响，这些影响的窒息阈值和重要的稳定机制的短时程增强的排泄输出。这种颈动脉化学感受器分离的狗模型也将用于解决中枢与外周低氧对睡眠中周期性呼吸的影响的问题。将研究第二个狗模型以及患有慢性心力衰竭的人类患者，以解决Cheyne-Stokes呼吸的机制，特别强调来自充血性心力衰竭患者肺部的额外刺激对过度通气的影响。最后，我们将使用狗和人--有和没有神经支配的肺--来说明睡眠期间非化学的机械感受器抑制反馈效应对上气道和泵肌的作用：a）上气道中高频低振幅压力振荡的影响; B）振幅的影响，正常碳酸血症机械通气的时间和持续时间对固有呼吸节律的重置和“短期抑制”的影响在阶段性抑制性感觉输入停止后呼吸运动输出的变化。这些在睡眠中进行的研究对于测试呼吸控制机制对机械反馈的敏感性很重要，这是一个相对未探索的问题，特别是在人类中。

During sleep and with the loss of the "wakefulness" drive to pump and upper airway respiratory muscles, the control of breathing becomes highly dependent upon and vulnerable to reflexive feedback inputs from chemoreceptors and mechanoreceptors. Accordingly, sleep-induced breathing instabilities are common and have a significant prevalence even in the general population. Sleep unmasks a highly sensitive hypocapnic-induced apneic threshold, but we do not know what role this mechanism plays in various types of sleep-disordered breathing, because we do not know its sites of action, its changes in sensitivity in the presence of powerful background influences such as CNS hypoxia, chronic hypocapnia/hypercapnia, changing sleep states, or changing stimuli to breathe which might be specific to sleep. We will use sleeping humans and dogs, the latter with extra corporeal perfusion of isolated carotid chemoreceptors-to quantify the effect of these influences on both the apneic threshold and on the important stabilizing mechanism of short term potentiation of ventilatory output. This dog model with isolation of carotid chemoreceptors will also be used to address the question of central versus peripheral hypoxic effects on periodic breathing in sleep. A second dog model as well as human patients with chronic heart failure will be studied to address the mechanisms of Cheyne-Stokes respiration, with specific emphasis on the effects of the added stimulus to hyperventilation originating from the lungs of the patient in congestive heart failure. Finally, we will use dogs and humans-with and without innervated lungs-to address the role of non-chemical, mechanoreceptor inhibitory feedback effects during sleep on upper airway and pump muscles; a) influences from high frequency low amplitude pressure oscillations in the upper airway; b) the effects of amplitude, timing and duration of normocapnic mechanical ventilation on the resetting of inherent respiratory rhythm and on the "short-term inhibition" of respiratory motor output following cessation of phasic inhibitory sensory input. These latter studies conduced in sleep are important to testing the sensitivity of respiratory control mechanisms to mechanical feedback-a problem which remains relatively unexplored, especially in the human.