The major goals of the proposed project are threefold. The first is to quantify the dynamic effects of respiration on heart rate control in subjects with obstructive sleep apnea syndrome (OSAS) during wakefulness and sleep. The second major objective is to assess the long-term effects of continuous positive airway pressure (CPAP) therapy on cardiorespiratory transfer in OSAS and to elucidate the mechanisms that may underlie these changes. The third goal is to develop a functional quantitative model that can characterize the complex dynamic coupling between respiration and heart rate control and enhance our understanding of the underlying physiological mechanisms. The dynamic model will relate fluctuations in heart rate to changes in: (a) instantaneous lung volume, (b) respiratory drive, and (c) arterial blood pressure. Normal non-snorers, hypertensive non-snorers, and OSAS patients before and after 6 months of CPAP therapy will be studied in 4 series of experiments. Changes in cardiorespiratory transfer due to OSAS and the efficacy of CPAP therapy in reducing these changes will be assessed by comparing the estimated model parameters and derived transfer functions across the subject groups. In Series 1a, cardiorespiratory transfer functions (CTF) will be estimated in wakefulness under spontaneous and controlled breathing conditions. In Series lb, CTF will be estimated in wakefulness and sleep, as well as during the application of the following interventions in sleep: hyperoxia, normoxic CPAP, and periodic acoustically-induced arousals during CPAP. In Series 2 and 3 a computer-controlled ventilator will provide randomized levels of respiratory assistance and randomly-occurring occlusions during various sleep stages. These perturbations will enhance the model-parameter estimation process by reducing correlation among the input variables. In Series 3 the autonomic responses to acoustically-induced arousals from sleep in OSAS subjects before and after 6 months of CPAP therapy will be compared. The methods validated in this study may provide an objective means of predicting in OSAS patients the risk of developing potentially fatal cardiac arrhythmias.
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