Arousal Threshold in the Pathogenesis of Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停发病机制中的唤醒阈值

• 批准号: 8377816
• 负责人: Atul Malhotra
• 金额: $ 30.08万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8377816
• 关键词: Acoustics; Adherence; Advocate; Affect; Apnea; Arousal; Attention; Basic Science; Brain Stem; Breathing; Carbon Dioxide; Cardiovascular system; Catecholamines; Clinical; Clinical Trials; Complex; Continuous Positive Airway Pressure; Data; Deposition; Dilator; Disease; Electroencephalography; Ethics; Event; Fatty acid glycerol esters; Female; Goals; High Prevalence; Human; Hypercapnia; Hypertension; Hypoxemia; Impairment; Individual; Lead; Literature; Logic; Mechanics; Muscle; Muscle function; Neurocognitive; Obstructive Sleep Apnea; Organ; Outcome; Pathogenesis; Patients; Pattern; Persons; Physiological; Predisposition; Prevalence; REM Sleep; Recruitment Activity; Recurrence; Reflex action; Regulation; Reporting; Research; Respiratory System; Rodent; Role; Severities; Sex Characteristics; Sleep; Sleep Apnea Syndromes; Staging; Stimulus; Stroke; Structure; Subgroup; Suction; Testing; Therapeutic Effect; Time; Trazodone; Wakefulness; Woman; base; cardiovascular risk factor; clinically relevant; cognitive function; craniofacial; esophagus pressure; falls; human subject; hypnotic; improved; insight; male; men; middle age; new therapeutic target; pharynx muscle; premature; pressure; prevent; research study; respiratory; respiratory reflex; response; sex; sleep onset; statistics; theories; therapeutic target; vehicular accident

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.

阻塞性睡眠呼吸暂停（OSA）是一种高度流行的疾病，主要与神经认知和心血管疾病有关。 后遗症尽管其后果得到承认，但对这种情况的治疗仍然是不可接受的， 现有的疗法耐受性差和/或具有高度可变的功效。唤醒的作用 阈值在OSA文献中受到的关注最少;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阻塞性睡眠呼吸暂停综合征。呼吸道的积累 睡眠时的刺激可以激活上气道肌肉，以保持咽部的通畅，但只有在以下情况下才能这样做， 有足够的时间可用于产生002和负压。也就是说，过早的觉醒可能 导致反复觉醒并阻止睡眠期间咽部开放的稳定。本 应用程序将研究OSA和匹配对照之间的唤醒阈值差异（目标1）， CPAP治疗OSA异常的可逆性（目的2）。非肌松催眠药的作用 还将从对上气道力学和控制的影响的角度评估治疗（目标3） 以及对短期临床结果的治疗效果（目的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的临床相关性， 臂旁复合体对睡眠觉醒的影响此外，我们建议的啮齿动物实验 合作者将提供对唤醒反应的机械见解，这将涉及研究， 在人类身上是可行的也是不道德的。因此，项目2将定义唤醒阈值在以下方面的潜在作用： OSA发病机制及其作为OSA治疗靶点的可行性，至少对于一个亚组的患者。