The objective of this proposed research is to improve our understanding of the resistance of upper airway and of the strength and electrical activation of its respiratory muscles in patients with obstructive sleep apnea (OSA). We will test 5 hypotheses. First that patients with OSA have a narrow airway with a high resistance and that this contributes to the development of OSA. A narrow airway would be more likely to collapse than would a normal sized one because it would have a lower pressure in it. Preliminary work supports this hypothesis but investigators have not controlled their studies for the effect of obesity, an accompanying feature of OSA. Resistance will be measured with the pulse flow method and with another more conventional method. Computed tomographic scans of the pharynx will access pharyngeal cross-sectional area. A second hyphothesis is that pharyngeal airway obstruction can be induced in awake patients with OSA but not in normals by the application of subatmospheric pressure to the nose during nasal breathing. Subjects lying on their back will wear a tightly fitting face mask in which the pressure is periodically lowered for 2 to 4 breaths to between - 10 and - 60 cmH2O. This may be a useful screening test for OSA, possibly eliminating many expensive and time consuming nocturnal sleep studies. It may also be useful to study the forcefulness of pharyngeal muscle contraction and the effect of pharmacologic agents and chemical stimuli on the pharyngeal airway. Third we will test the hypothesis that there is an inverse relationship between upper airway resistance during sleep and genioglossal and alae nasi electromyograms (EMG's ). We will also try to determine whether the observed decreased upper airway muscle EMG signals during apneic episodes could be produced by muscle fatigue. This will be tested by loading and fatiguing upper airway dilator muscles in normal subjects. Fourth we will test the hypothesis that treatment with weight loss, progesterone and protriptyline alters pharyngeal airway resistance and the ability of the airway to resist collapse from the application of subatmospheric pressure. Double blind cross over comparisons with placebo will be performed with progesterone and protriptyline. The fifth hypothesis we will test is that sleep deprivation or fragmentation, an important feature of the sleep syndrome, increase pharyngeal airway resistance and decreases the ability of the pharynx to resist collapse from the application of subatmospheric pressure in normal subjects.
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