The proposed research is based on the general hypothesis that laryngeal and pharyngeal muscles that exhibit phasic expiratory activity have an important role in the regulation of respiration in physiologic and pathophysiologic states. Previous animal and human studies from this and other laboratories indicate that laryngeal adductor muscles help actively brake exhalation regulating lung volume and the time of expiration. In contrast to the laryngeal adductors, relatively little is known about the factors controlling pharyngeal muscles with phasic expiratory activity such as the pharyngeal constrictor (PC) muscles and their role in respiration. It has been assumed that the PC muscles constrict the airway and it has been speculated that they promote upper airway closure during sleep. In contrast, we hypothesize that under conditions of pharyngeal airway narrowing, PC muscles actually dilate and stiffen the airway. Their dilating and stiffening action would lower airway closing pressure helping to maintain airway patency. Previous studies from our laboratory have determined the respiratory- related activity of laryngeal adductors in human subjects. The proposed protocols in decerebrate cats are designed to test the following hypotheses regarding the mechanisms controlling laryngeal adductor muscle activation: 1) different laryngeal adductors have similar responses to decreased lung volume, 2) phasic and tonic volume feedback regulate lung volume during expiration by reflexly modulating motor output to laryngeal adductors, and 3) the increase in laryngeal adductor activity associated with a decrease in end-expiratory lung volume is primarily mediated by unmyelinated thoracic vagal afferents. Our animal model will also be used to test the following hypotheses regarding the PC muscles: 1) the PCs exhibit respiratory-related activity and respond to a variety of respiratory stimuli, and 2) PC activation dilates and stiffens the narrowed pharyngeal airway. The former hypothesis will also be tested in normal human subjects during wakefulness and sleep. To test our hypothesis that activation of the PC muscles has a protective rather than a punitive role in the maintenance of upper airway patency during sleep, PC activity will be recorded during nighttime polysomnograms in patients with obstructive sleep apnea and high upper airway resistance syndrome. Preliminary results of the proposed protocols indicate that respiratory stimuli have different effects on the activation of laryngeal adductor and PC muscles supporting our hypothesis that the two sets of upper airway expiratory muscles have different roles in the control of respiration. Nevertheless, results for a given upper airway muscle are very similar in decerebrate cats and human subjects. This close correlation in responses will allow an exploration in animal experiments of the possible mechanisms underlying observations made in humans.
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