CAUSES OF SLEEP-INDUCED BREATHING INSTABILITIES

睡眠引起的呼吸不稳定的原因

• 批准号: 2839896
• 负责人: Jerome A Dempsey
• 金额: $ 31.94万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2839896
• 关键词: REM sleep; carotid body; cerebral ischemia /hypoxia; chemoreceptors; clinical research; congestive heart failure; disease /disorder etiology; dogs; electromyography; human subject; hyperpnea; hypocapnia; hypoxia; isolation perfusion; mechanoreceptors; pulmonary respiration; respirators; respiratory airflow disorder; respiratory airflow measurement; respiratory airway pressure; sleep; sleep apnea; sleep disorders; vagus nerve; wakefulness

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.

在睡眠期间，随着泵和上呼吸道呼吸肌的“清醒”驱动力的丧失，呼吸的控制变得高度依赖于化学感受器和机械感受器的反射反馈输入，并且容易受到这种反馈输入的影响。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。睡眠揭示了高度敏感的低碳酸血症引起的呼吸暂停阈值，但我们不知道这种机制在各种类型的睡眠呼吸障碍中发挥什么作用，因为我们不知道它的作用部位，也不知道它在中枢神经系统缺氧、慢性低碳酸血症/高碳酸血症、改变睡眠状态或改变可能特定于睡眠的呼吸刺激等强大背景影响下的敏感性变化。我们将使用熟睡的人和狗，对后者进行体外灌注分离的颈动脉化学感受器，以量化这些影响对呼吸暂停阈值和通气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与外周缺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，以解决潮式呼吸的机制，特别强调附加刺激对充血性心力衰竭患者肺部过度通气的影响。最后，我们将使用狗和人类（无论是否有神经支配的肺部）来解决睡眠期间非化学机械感受器抑制反馈效应对上呼吸道和泵肌的作用； a) 上呼吸道高频低振幅压力振荡的影响； b) 正常二氧化碳机械通气的幅度、时间和持续时间对固有呼吸节律的重置以及对阶段性抑制性感觉输入停止后呼吸运动输出的“短期抑制”的影响。后面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非常重要，这是一个相对尚未探索的问题，尤其是在人类中。