CAUSES OF SLEEP-INDUCED BREATHING INSTABILITIES

在睡眠期间，随着泵和上呼吸道肌肉的“清醒”动力的丧失，呼吸的控制变得高度依赖和容易受到化学感受器和机械感受器的反射性反馈输入的影响。因此，睡眠引起的呼吸不稳定很常见，甚至在普通人群中也很普遍。睡眠揭示了一种高度敏感的低碳酸血症诱导的呼吸暂停阈值，但我们不知道这一机制在各种类型的睡眠障碍呼吸中起什么作用，因为我们不知道它的作用部位，也不知道它在强大的背景影响下的敏感性变化，如中枢神经系统缺氧、慢性低碳酸血症/高碳酸血症、睡眠状态的变化或呼吸刺激的变化，这些可能是睡眠特有的。我们将使用睡眠中的人和狗，后者使用分离的颈动脉化学感受器进行额外的身体灌流-来量化这些影响对呼吸暂停阈值和对呼吸输出短期增强的重要稳定机制的影响。这种分离颈动脉化学感受器的狗模型也将用于解决中枢和外周低氧对睡眠中周期性呼吸的影响的问题。第二个狗模型以及患有慢性心力衰竭的人类患者将被研究，以解决Cheyne-Stokes呼吸的机制，特别强调额外的刺激对充血性心力衰竭患者肺部过度换气的影响。最后，我们将利用狗和人--有无肺部神经支配--来研究睡眠期间非化学、机械感受器抑制性反馈效应对上呼吸道和泵肌的作用；a)上呼吸道高频低幅度压力振荡的影响；b)常压机械通气的幅度、时间和持续时间对固有呼吸节律的恢复以及停止相性抑制感觉输入后对呼吸运动输出的“短期抑制”的影响。这些在睡眠中进行的后一项研究对于测试呼吸控制机制对机械反馈的敏感性非常重要--这一问题仍然相对未被探索，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.