MECHANISMS OF RESPIRATORY DYSRHYTHMIA IN SLEEP

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Multiple factors interact to influence respiratory output in sleep. This proposal deals with three factors which have been less studied in sleep but which are hypothesized to be significant contributors to the generation or perpetuation of respiratory dysrhythmias in this state. These factors are changes in brain blood flow during sleep, the effect of sleep on the strength of respiratory afterdischarge, and the presence of an oscillatory respiratory stimulus in the awake and sleeping subject. The experiments proposed will investigate the respiratory consequences of altering cerebral perfusion during slow wave and REM sleep under conditions of hypoxia and hypercapnia, the possibility that sleep with or without hypoxia impairs respiratory afterdischarge and, if so, whether sexual differences exist in this response, and how oscillations in an otherwise persistent respiratory stimulus may cause episodic hypoventilation. The studies are to be performed in the unanesthetized awake and sleeping goat. This species is ideal for the proposed studies for the following reasons: (a) its unique cerebrovascular anatomy allows continuous, dynamic measurement of brain blood flow and when necessary, its control, which is not possible with other methods; (b) it demonstrates reproducible respiratory afterdischarge using a localized carotid body stimulus; and (c) it has well-characterized electrometric and ventilatory changes during wakefulness, slow wave and REM sleep that are similar to human beings. Sleep-disordered breathing is a relatively common disease with significant morbidity and mortality. Because its pathogenesis remains unclear, therapy remains less than ideal. The proposed studies should help in the understanding of factors that lead to the genesis of respiratory dysrhythmias in sleep.