SEGMENTAL CONTROL OF PHARYNGEAL COLLAPSIBILITY

阻塞性睡眠呼吸暂停是肥胖中年男性的常见疾病。 它 是由于当咽部气道 在睡眠中崩溃。 虽然崩溃的机制尚不清楚，但我们 已经发展出上气道作为一个 可折叠导管（Starling电阻器）。 在人类和动物中 研究，我们已经证明了气流动力学， 那些在简单的可折叠导管中的（斯特林电阻器）。 具体地说， 塌陷发生在一个离散的限流部位（FLS）， 睡眠时的气流。 此外，我们已经表明， FLS的可调节性导致睡眠期间气流减少。 在目前的提案中，这项工作将扩大到确定更多的 准确地说，在FLS调节气道可膨胀性的因素。 具体地，现在认识到FLS可以发生在 口咽或鼻咽。 虽然在变化的原因， FLS的位置不清楚，可以假设FLS发生在 最容易塌陷的咽部 主要的假设是 建议口咽和鼻咽的可吸收性是 由咽部结构和肌肉不同地调节。 在特定 目标#1，我们将确定位置的结构基础， 在隔离猫上呼吸道研究中FLS的塌陷性。 在具体目标#2中，我们将确定改变的机制， 当神经肌肉活动时， 受刺激 在每一个具体目标中， 特定咽部节段的可吸收性将在 隔离猫上呼吸道。 然后将在人类中进行研究， 确定异常的结构和神经肌肉基础， 呼吸暂停患者的上气道功能。 该提案基于 猫和睡眠中人咽部气流动力学的相似性 确定肥胖在上气道发病机制中的作用 睡眠中的障碍

Obstructive sleep apnea is a common disorder of obese middle-age men. It is due to airflow obstruction that results when the pharyngeal airway collapses during sleep. While the mechanism for collapse is not clear, we have developed the concept that the upper airway functions as a collapsible conduit (Starling resistor). In both human and animal studies, we have demonstrated airflow dynamics that are comparable to those in a simple collapsible conduit (Starling resistor). Specifically, collapse occurs at a discrete flow-limiting site (FLS) that obstructs airflow during sleep. Moreover, we have shown that increases in the collapsibility of the FLS lead to reductions in airflow during sleep. In the current proposal, this work will be extended to determine more precisely the factors that modulate airway collapsibility at the FLS. Specifically, it is now recognized that the FLS can occur in either the oropharynx or nasopharynx. Although the reason for variability in the location of the FLS is not clear, it can be assumed that the FLS occurs in the most collapsible pharyngeal segment. The major hypothesis of this proposal is that the collapsibility of the oropharynx and nasopharynx is modulated differently by pharyngeal structures and muscles. In Specific Aim #1, we will determine the structural basis for the location and collapsibility of the FLS in studies in the isolated feline upper airway. In Specific Aim #2, we will determine the mechanism for alterations in the location and collapsibility of the FLS when neuromuscular activity is stimulated. In each specific aim, mechanisms controlling the collapsibility in specific pharyngeal segments will be elucidated in the isolated feline upper airway. Studies will then be extended in humans to determine the structural and neuromuscular basis for abnormalities in upper airway function in apneic patients. This proposal builds on similarities in pharyngeal airflow dynamics in the cat and sleeping human to determine the role of adiposity in the pathogenesis of upper airway obstruction during sleep.