Obstructive sleep apnea (OSA) is a common and potentially life- threatening disorder which is characterized by periodic cessation of effective respiration (apnea) during sleep. The resultant nocturnal hypoxia and sleep disruption lead to the serious sequelae of the syndrome which include profound daytime hypersomnolence, intellectual deterioration, and cardiopulmonary failure. Despite a vigorous and growing interest in this disorder, the pathogenesis of OSA remains poorly understood. The fundamental feature of most apneas is complete occlusion of the pharynx. Pharyngeal occlusion is a """"""""state-dependent"""""""" event which occurs only during sleep and often requires arousal for termination. Therefore, sleep influences on the muscular forces controlling pharyngeal patency are likely to be crucial. Unfortunately, we understand very little about the muscular control of the human pharynx and less about how sleep influences human upper airway muscle activation and pharyngeal airway stability. As a result, this proposal includes a series of protocols designed to examine the influence of sleep on upper airway muscular mechanics and respiration in normal humans and in patients with obstructive sleep apnea. The following major hypotheses will be addressed: 1) pharyngeal muscle activity is significantly reduced or altered during normal human sleep in comparison with wakefulness, 2) sleep-related changes in pharyngeal muscle activation are closely correlated with the increase in upper airway resistance known to occur during normal sleep, 3) subjects with epidemiologic risk factors for obstructive sleep apnea (male gender, age, and obesity) have a greater propensity for sleep- related upper airway collapse resulting from sleep influences on pharyngeal muscular forces, and 4) OSA patients have abnormal sleep-related changes in upper airway muscle activation which allow complete upper airway collapse to occur during sleep. Three pharyngeal muscle groups known to exhibit phasic activation with inspiration will be investigated. These muscles (genioglossus, geniohyoid, and tensor palatini) are strategically positioned to influence the collapsible pharynx at three important levels. The long-term objective of these studies is to improve our understanding of the mechanisms responsible for the development of periodic upper airway collapse sleep in this patient population.
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