The mechanism(s) underlying the increase in upper airway resistance during sleep is unclear. The overall objective of this proposal is to study the determinants of pressure-flow relationships in the nasal, pharyngeal and laryngeal upper airway compartments during wakefulness, slow wave sleep and rapid eye movement sleep. It is widely believed that the principal determinant of inspiratory resistance in the upper airway is the balance between the collapsing pressure generated by the inspiratory pump muscles and the dilating forces generated by upper airway dilator muscles. Specific experiments are proposed to determine how upper airway muscles and diaphragm may be differentially activated by various respiratory stimuli relevant to upper airway occlusion. These experiments will be performed in adult goats. This model is particularly well suited for these studies because multiple upper airway muscle activities and pressures can be studied chronically, and constant head position can be maintained with a traumatic restraint in a natural sleeping posture. Initial experiments will determine the effects of direct electrical stimulation of individual upper airway muscles on compartmental pressure-flow relationships in anesthetized, paralyzed animals with isolated upper airways. Subsequently, in unanesthetized goats, measurements of compartmental inspiratory pressure-flow relationships will be compared with simultaneous EMG activities and lengths (by sonomicrometry) of the most mechanically relevant dilators of the nasal (alae nasi), pharyngeal (genioglossus, hyoid and palatal muscles), and laryngeal (posterior cricoarytenoid, cricothyroid) compartments during eupnea and during progressive hypercapnia or hypoxia in each sleep-wake state. Changes in compartmental resistance and dilator EMG activities and lengths during inspiratory flow-resistive loading will also be examined. Finally, the central neural effects of hypoxia independent of peripheral chemoreceptor activation on relative activation of upper airway and diaphragm muscles will be determined during sleep. Better understanding of these factors may provide considerable insight into the pathophysiology of the obstructive sleep apnea syndrome.
