SLEEP, AIRWAY PATENCY AND THE PHARYNGEAL MUSCULATURE

睡眠、气道通畅和咽部肌肉组织

• 批准号: 6777525
• 负责人: David P. White
• 金额: $ 42.38万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-20 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6777525
• 关键词: androgen inhibitor; carbon dioxide; clinical research; electromyography; hormone regulation /control mechanism; human subject; hypogonadism; local anesthesia; muscle pharmacology; neuroregulation; nuclear magnetic resonance spectroscopy; obesity; pharynxs; polycystic ovary syndrome; polysomnography; postmenopause; respirators; respiratory function; respiratory muscles; respiratory reflex; sleep apnea; testosterone

Obstructive sleep apnea (OSA) is a common, debilitating disorder characterized by recurrent collapse of the pharyngeal airway during sleep. This leads to both sleep fragmentation as arousal is required to terminate these events and the sequelae of recurrent hypoxia and hypercapnia. Thus, afflicted individuals are somnolent during the day due to sleep fragmentation and may be at increased risk for hypertension, myocardial infarction or stroke. Our current understanding of the pathophysiology of this disorder is incomplete but suggests that reduced pharyngeal airway size in concert with sleep-induced changes in pharyngeal dilator muscle activation lead to airway collapse during sleep. Our current protocols have three specific goals: 1. Neural Control of Pharyngeal Muscle Activation - We hope to better define the mechanisms controlling upper airway muscle activity awake and asleep using novel approaches which allow up to precisely control airway pressure and flow as we examine the EMG of two pharyngeal muscles. 2. Testosterone and Apnea Pathogenesis: Sleep apnea is well known to be more common in men than women, although the mechanistic explanation for this observation remains unclear. We have designed a series of studies to carefully examine the effects of testosterone on pharyngeal muscle activity, airway anatomy (MRI) and ventilatory stability (loop gain) in several populations in whom testosterone levels can be manipulated relatively easily. 3. Obesity and Apnea Pathogenesis: As with male gender, obesity is a very common trait in sleep apnea. However, the mechanism by which obesity leads to airway obstruction during sleep remains unresolved. We, therefore, plan to assess the impact of surgically-induced weight loss not only on sleep apnea severity but on pharyngeal muscle activation and control, upper airway anatomy (MRI/CT), and ventilatory control stability (loop gain). The latter two protocols should not only improve our understanding of the mechanisms influencing apnea epidemiology, but also allow us to begin to build multi-variant predictive models of apnea pathogenesis incorporating the three relevant variables (anatomy, airway motor control and respiratory control stability). This should substantially improve our understanding of this disorder.

阻塞性睡眠呼吸暂停 (OSA) 是一种常见的使人衰弱的疾病，其特征是睡眠期间咽部气道反复塌陷。 这会导致睡眠碎片化（因为需要唤醒才能终止这些事件）以及反复缺氧和高碳酸血症的后遗症。 因此，患者白天由于睡眠碎片化而嗜睡，患高血压、心肌梗塞或中风的风险可能增加。 我们目前对这种疾病的病理生理学的理解并不完整，但表明咽部气道尺寸的减小与睡眠引起的咽部扩张肌激活的变化相一致，导致睡眠期间气道塌陷。我们目前的协议有三个具体目标： 1. 咽部肌肉激活的神经控制 - 我们希望使用新颖的方法更好地定义控制清醒和睡眠时上呼吸道肌肉活动的机制，这些方法可以在我们检查肌电图时精确控制气道压力和流量两块咽肌。 2. 睾酮和呼吸暂停发病机制：众所周知，睡眠呼吸暂停在男性中比女性更常见，尽管这一观察结果的机制解释仍不清楚。 我们设计了一系列研究，仔细检查睾酮对几个睾酮水平相对容易控制的人群的咽肌活动、气道解剖学 (MRI) 和通气稳定性（循环增益）的影响。 3. 肥胖和呼吸暂停发病机制：与男性一样，肥胖是睡眠呼吸暂停的一个非常常见的特征。 然而，肥胖导致睡眠期间气道阻塞的机制仍未解决。 因此，我们计划评估手术引起的体重减轻不仅对睡眠呼吸暂停严重程度的影响，而且对咽部肌肉的激活和控制、上呼吸道解剖学 (MRI/CT) 和通气控制稳定性（循环增益）的影响。后两个协议不仅应该提高我们对影响呼吸暂停流行病学的机制的理解，而且还使我们能够开始建立结合三个相关变量（解剖学、气道运动控制和呼吸控制稳定性）的呼吸暂停发病机制的多变量预测模型。 这应该会大大提高我们对这种疾病的理解。