SCOR IN CARDIOPULMONARY DISORDERS OF SLEEP

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The research proposed in this SCOR Renewal Proposal is aimed at the basic mechanisms, epidemiology and clinical consequences of sleep disordered breathing (SDB) and its treatment. 1. We will investigate the mechanisms by which the respiratory events which accompany SDB cause sustained hypertension. The hypothesis that an augmented carotid chemo-reflex sensitivity produces chronic elevations in sympathetic vaso motor outflow, and peripheral vascular resistance will be tested in humans and chronically-instrumented sleeping and anesthetized dogs. We will emphasize the role of "sensitization" of the carotid chemoreceptor in response to sustained, intermittent asphyxia as a major determinant of sustained hypertension. 2. We will determine - using the sleeping dog and human - those mechanisms which initiate and perpetuate sleep-induced instability of respiratory motor output and central apnea. We will also determine the influence of inhibition of respiratory motor output and central apnea on patency of the upper airway in human subjects who very widely in their susceptibility to upper airway obstruction. 3. We propose to continue to study the epidemiology of SDB with the aim of accumulating data from over night polysymography over a 5-9 year span in our cohort of 800 employed men and women with a wide range of SDB. These longitudinal data will permit us to address the pathophysiologic significance of mild, asymptomatic SDB and to investigate etiologic mechanisms. Based on our 4 years of cross-sectional data, we propose to use longitudinal studies to focus on specific questions of greatest relevance to public health, namely: the roles of aging and menopause in the development of SDB and the effect of SDB on hypersomnolence and systemic hypertension. 4. We will determine the cellular mechanisms responsible for nocturnal asthma. Our specific hypothesis focuses on the independent and interactive effects of sleep and circadian changes in cortisol and epinephrine on airway broncho-constriction and airway inflammation. 5. We will to develop computer-assisted methods for use in the efficient, accurate analysis of SDB. Specifically we will complete and extend our development of a Sleep Analysis Program for purposes of computer based quantitation of cardio-pulmonary events which occur in sleep and for the analysis of sleep state instability and continuity.