Assessment of Upper Airway Mechanics Using Newer EMG Techniques

描述（由申请人提供）：近期目标：将新的肌电图技术应用于上气道肌肉，以确定阻塞性睡眠呼吸暂停的重要治疗靶点。职业发展目标：为学员提供充足的指导时间和研究活动。研究项目：阻塞性睡眠呼吸暂停是一种重要的疾病，由于其高患病率和良好的神经认知和心血管后遗症。这种疾病的治疗仍然存在问题，因为现有的治疗方法要么耐受性差，要么疗效不一，导致许多人主张进一步研究其潜在机制。先前的研究已经确定了上气道肌肉（如颏舌肌和腭张肌）在睡眠呼吸暂停发病机制中的重要性。然而，多单元肌电图记录提供了无数运动单元的平均表示，产生了关于单个运动单元行为的相当不完整的信息。我们已经开始了一系列的研究，使用肌电图的高频采样来定义颏舌肌内的各种运动单位。这些较新的研究揭示了颏舌肌行为的显著复杂性，有6种不同的放电模式可识别。因此，颏舌肌多单元肌电图的上升或下降很难解释，因为这些变化可能是由许多单个运动单元放电变化中的任何一个介导的。我们已经观察到特定的单位，可能是最关键的维持咽通畅。因此，这样的单位将成为我们可以与神经解剖学合作者解决的合乎逻辑的治疗目标。我们也开始使用单纤维肌电图和宏观肌电图进行研究，以期对各种上呼吸道肌肉进行更多的定量评估。这些新的肌电图技术将使我们能够评估睡眠呼吸暂停患者肌电图中与对照组相比的高水平活动的机制，因为目前关于这种高活动是代表肌肉的高中枢驱动还是去神经支配的影响仍存在争议。这个K24奖将使我们能够追求有趣的假设，这些假设可能最终导致睡眠呼吸暂停的新疗法，但肯定会对疾病的发病机制产生深入的了解。该奖项还将允许PI投入更多的时间来培训睡眠和呼吸生理学领域的年轻研究者。对研究者管道的需求已被称为危机（Sleep. 2006 29:1260）相关性（见说明）：阻塞性睡眠呼吸暂停与机动车事故、高血压和中风密切相关。一个人从睡眠中醒来的容易程度（唤醒阈值）可能是睡眠呼吸暂停发生的重要原因。我们建议研究唤醒阈值的作用，最终目标是开发新的治疗睡眠呼吸暂停的方法，以防止其严重并发症。（摘要结束）

DESCRIPTION (provided by applicant): Immediate goals: To apply newer electromyographic techniques to upper airway muscles with a view towards identifying important therapeutic targets in obstructive sleep apnea. Career development goals: To provide sufficient time for mentoring of trainees and research activities. Research project: Obstructive sleep apnea is an important disease due to its high prevalence and well established neurocognitive and cardiovascular sequelae. Treatment of this disease remains problematic since the existing therapies are either poorly tolerated or have variable efficacy, leading many to advocate for further research into underlying mechanisms. Prior research has established in the importance of the upper airway muscles (such as the genioglossus and tensor palatini) in the pathogenesis of sleep apnea. However, multi-unit electromyographic recordings provide an average representation of innumerable motor units yielding fairly incomplete information about the behavior of individual motor units. We have begun a series of studies using high frequency sampling of the electromyogram to define the various motor units within the genioglossus muscle. These newer studies have revealed marked complexity in the behavior of the genioglossus muscle, with 6 distinct firing patterns being identifiable. A rise or fall in the genioglossal multiunit EMG is therefore difficult to interpret since these changes could be mediated by any of a number of individual motor unit firing changes. We have observed specific units that may be most critical for the maintenance of pharyngeal patency. Such units would thus we logical therapeutic targets which we can address with our neuroanatomy collaborators. We have also begun studies using single fiber EMGs and MacroEMGs which a view towards performing more quantitative assessments of various upper airway muscles. These newer EMG techniques will allow us to assess the mechanisms underlying the high level of activity seen in the EMG of sleep apnea patients as compared with controls, since there is currently an ongoing controversy as to whether this high activity represents high central drive to the muscle versus an effect of denervation. This K24 award would allow us to pursue interesting hypotheses that may ultimately lead to new treatments for sleep apnea, but will certainly yield insights into disease pathogenesis. This award will also allow the PI to dedicate more time to training young investigators in the field of sleep and respiratory physiology. The need for an investigator pipeline has been termed a crisis (Sleep. 2006 29:1260) RELEVANCE (See instructions): Obstructive sleep apnea is strongly implicated in motor vehicle accidents as well as high blood pressure and stroke. How easily an individual wakes up from sleep (arousal threshold) is something that may be important in why sleep apnea occurs. We propose studies that will examine the role of the arousal threshold with an ultimate goal of developing new treatments for sleep apnea to prevent its serious complications. (End of Abstract)