The intermittent occlusion of the upper airway in patients with the obstructive sleep apnea syndrome results in considerable morbidity: hypoxia, hypercapnia, cardiac arrhythmias, cor pulmonale, polycythemia, and a variety of neuropsychiatric manifestations. Differences in the electrical responses to chemical and mechanical stimuli of the upper airway and thoracic muscles have been implicated in the pathogenesis of obstructive sleep apneas; the proposed studies will help define the mechanical correlates of the neural activation of the upper airway muscles. In spontaneously breathing anesthetized dogs, the mechanical output of upper airway muscles will be assessed by measuring upper airway muscle length changes (using sonomicrometry) and upper airway resistance continuously throughout the respiratory cycle, and these mechanical events will be compared to simultaneously recorded upper airway muscle electromyographic activity. Specifically, these studies will (1) define the relationship between phasic and tonic changes in upper airway muscle activity (electrical activity and shortening), and changes in nasal, pharyngeal and laryngeal resistance during the respiratory cycle, and delineate how these relationships are affected by chemically and reflexly stimulated breathing; (2) compare how different upper airway muscles respond electrically and mechanically to stimulation of chemoreceptors and mechanoreceptors, and assess the effects of these stimuli on upper airway resistance at the nose, pharynx and larynx; (3) define the effects of positive and negative upper airway pressure changes on upper airway resistance, resting upper airway muscle lengths, and the phasic and tonic activation of upper airway muscles; and (4) characterize how activation of single upper airway muscles (by electrical stimulation) affects upper airway resistance, how the different upper airway muscles act together to increase upper airway size, and how changes in resting position and length of these muscles affect their mechanical actions and neural activation. In addition, isolated upper airway muscles obtained from anesthetized rats and dogs will be studied in vitro to assess their length-tension and force-frequency relationships, and their fatigue characteristics; and these findings will be compared to the force generating capacity and fatigue characteristics of the diaphragm.
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