We propose further study of the regulation of breathing in various physiologic states in unanesthetized humans and dogs with specific emphasis on the underlying mechanisms and the mechanical consequences. To this end, the goals and procedures of this proposed research are as follows: 1. To determine the limits of the healthy pulmonary control system for gas transport, for respiratory muscle pressure development and for ventilatory output at extraordinarily elevated levels of metabolic demand. We hypothesize that limitations to function in the pulmonary control system will be manifested and will present significant limitations to maximum oxygen consumption, as the level of cardio-vascular and locomotor muscle fitness is increased in young (20-30 yrs) and elderly (55-75 yrs) highly endurance trained athletes, in the elite asthmatic athlete and in the racing greyhound. Special emphasis will be focused on alveolar to arterial gas exchange and on the mechanical constraints imposed by the chest wall on alveolar hyperventilation in heavy exercise. 2. To determine the effects of various types of acute and chronic ventilatory stimuli and inhibitors on respiratory muscle recruitment, on respiratory muscle length and on the timing of neuro-mechanical coupling throughout the breath. Physiologic states to be studied include acute and chronic chemoreceptor stimulation, locomotion and internal mechanical loading and unloading. These studies will also address the feed-forward and feed-back mechanisms responsible for these patterns of recruitment and the mechanical consequences of this recruitment to lung and chest wall function. 3. To quantitate the effects of sleep-induced increases in airway resistance on CO2 retention and respiratory muscle recruitment. Two closely related effects of sleep state will also be studied: a) the selective responses of inspiratory, expiratory abdominal and rib cage and upper airway """"""""respiratory"""""""" muscles to inhibition secondary to small reductions in PaCO2 and to mechanical """"""""unloading"""""""" in sleep; and b) the role of carotid chemoreceptors in the mediation of hypocapnic inhibition during all sleep stages.
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