Breathing is controlled by a central neural oscillator that produces rhythmic output to the respiratory muscles. Pathological disturbances in rhythm (dysrhythmias) are commonly observed in clinical practice. The mechanisms responsible for genesis of respiratory dysrhythmias are poorly understood. The present studies take a novel approach to this problem. The basic postulate is that the rhythm of the respiratory oscillator can be altered by a variety of stimuli, arising from peripheral or central neural pathways. The long-range hypothesis of this proposal is that respiratory dysrhythmias can be induced by stimuli that impinge upon or arise within the respiratory oscillator at a specific time in the respiratory cycle, the phase of vulnerability. Human studies are performed in healthy adults and in pre-term infants. Animal studies are performed in anesthetized or decerebrate preparations; neural respiratory rhythm is represented by phrenic nerve activity, allowing use of open-loop experimental conditions which avoid negative chemical feedback associated with changes in ventilation.
Specific aims are: 1) to analyze phase resetting of respiratory rhythm by swallowing in animals and adult humans. The hypothesis is that an afferent signal arising from the airway is responsible for maintaining the normally strong interaction between swallowing and breathing, and that loss of this signal results in increased vulnerability for aspiration and respiratory dysrhythmias induced by swallowing during a vulnerable phase of the respiratory cycle; 2) to determine how neural maturation influences phase resetting and dysrhythmias of the respiratory oscillator in animals of different ages, and to evaluate the hypothesis that underdeveloped neural circuits of the immature respiratory oscillator make its rhythm susceptible to annihilation by perturbations that impinge upon or arise within the oscillator; 3) to develop a treatment for apnea of prematurity, and to test the hypothesis that the dysrhythmic state can be reversed back to the rhythmic state by properly """"""""tuned"""""""" tactile stimuli. These studies should lead to greater understanding of rhythmicity and integrative responses of the respiratory control system, and provide insight into disturbances in control mechanisms that cause apnea and aspiration in clinical disease states.
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