Arousal Threshold in the Pathogenesis of Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停(OSA)是一种高度流行的疾病，主要表现为神经认知和心血管疾病 后遗症。尽管已认识到其后果，但这种情况的治疗仍然是不可接受的 现有的治疗方法耐受性差和/或疗效参差不齐。唤醒的作用 阈值在OSA文献中得到的关注很少；尽管最近认识到 从睡眠中醒来可能有一个主要的病理生理作用是OSA。呼吸系统的蓄积 睡眠中的刺激可以激活上呼吸道肌肉以保持咽部通畅，但只有在 有足够的时间给002和负压发展。也就是说，过早醒来可能会 导致反复唤醒，并防止睡眠期间咽部通畅的稳定。现在 应用程序将研究OSA和匹配对照组(目标1)在唤醒阈值上的差异，以及 CPAP治疗阻塞性睡眠呼吸暂停的可逆性(目标2)。非肌松剂催眠药的作用 治疗也将从对上主干道力学和控制的影响的角度进行评估(目标3)。 和近期临床结果的疗效(目标4)。我们的研究将与所有 本PPG中的其他项目通过提供与基础研究有关的临床相关性的作用 从睡眠中唤醒时的臂旁复合体。此外，本署拟进行的啮齿动物实验 合作者将提供对唤醒反应的机械性见解，这既不涉及研究 在人类身上既不可行也不合乎道德。因此，项目2将定义觉醒阈值在 OSA的发病机制及其作为OSA治疗靶点的可行性，至少对一组患者是如此。

Obstructive sleep apnea (OSA) is a highly prevalent condition with major neurocognitive and cardiovascular sequelae. Despite its recognized consequences, the treatment of this condition remains unacceptable as the existing therapies are poorly tolerated and/or have highly variable efficacy. The role of the arousal threshold has received minimal attention in the OSA literature; despite recent recognition that the propensity to wake up from sleep may have a major pathophysiological role is OSA. The accumulation of respiratory stimuli during sleep can activate upper ainway muscles to preserve pharyngeal patency, but can only do so if sufficient time is available for 002 and negative pressure to develop. That is, premature awakening could lead to recurrent arousals and prevent the stabilization of pharyngeal patency during sleep. The present application will study differences in arousal threshold between OSA and matched controls (Aim 1), and the reversibility of abnormalities in OSA with CPAP therapy (Aim 2). The role of non-myorelaxant hypnotic therapy will also be assessed from standpoint of the effects on upper ainway mechanics and control (Aim 3) and therapeutic effects on short-term clinical outcome (Aim 4). Our research will interact heavily with all of the other Projects within this PPG by providing clinical relevance to the basic research regarding the role of the parabrachial complex on arousal from sleep. In addition, the proposed rodent experiments by our collaborators will provide mechanistic insights into the arousal response which would involve studies neither feasible nor ethical in humans. Project 2 will therefore define the potential role of the arousal threshold in OSA pathogenesis and its viability as a therapeutic target in OSA, at least for a subgroup of patients.