ETHANOL AND RESPIRATORY DRIVE DURING SLEEP

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Ethanol (E) is a respiratory depressant and respiratory failure is the major cause of death in E overdose. The respiratory responses to hypercapnia and to hypoxia are depressed by E in a dose-dependent manner, even at serum alcohol levels commonly seen in social drinkers. Sleep likewise depresses respiratory responses to hypoxia and hypercapnia. It is unknown what are the combined effects of sleep and ethanol on respiratory drive. Also unknown are the possible changes in susceptibility to these effects of E in subjects with underlying cardiopulmonary problems, especially those subjects with sleep-related respiratory symptoms such as snoring and sleep apnea. This small grant application is for interim funds to further develop a broad collaborative research program on E and the control of breathing during sleep. The applicant scientists are new to the field of alcohol research but they are experienced in studies on the control of respiration in humans during wakefulness and sleep. Their first work on this topic demonstrated that in males who habitually snore, E increases upper airway resistance (measured by the nasal continuous positive airway pressure required to eliminate snoring) and can cause sleep apnea. They will extend their work with more sensitive measurements of respiratory drive that are applicable to nonsnorers. Measurements will include inspiratory occlusion pressure, total respiratory resistance and ventilatory response to hypercapnia and isocapnic hypoxia in addition to observation of phenomena associated with respiratory depression (periodic breathing, hypopneas or apneas and desaturations). These studies will allow differentiation of the contributions of increased upper airways resistance and reduced respiratory drive to the increase in sleep disordered breathing produced by E. Preliminary results have been obtained in 8 young nonobese non snoring men. Further studies are planned on snorers, older normal subjects and in patients with mild obstructive sleep apnea.