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.
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