SHORT-TERM MODULATION OF AUTONOMIC FUNCTION

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During the past 3 years, I have been developing a new means of understanding cardiovascular physiology by examining the dynamic variability involved in the regulation of heart rate, arterial blood pressure and respiration. The approach applies basic principles of mathematics and physics employed in control system theory in fields such as electrical engineering to the analysis of cardiovascular homeostasis, and it represents a clear divergence from the more descriptive approach traditionally used by physiologists and physicians. The studies described in this proposal will apply a unique broad-band excitation technique, which was previously used to characterize respiratory modulation of autonomic outflow in humans, to the analysis of baroreflex regulation of heart rate and arterial blood pressure. The most notable features of the work are the combined application of sophisticated signal processing techniques with microneurographic recordings to evaluate beat- to-beat regulation of autonomic outflow to he sino-atrial node and the peripheral vasculature, and to obtain an accurate assessment of the close- and open-loop frequency response of the baroreflex during manipulations of the mean point around which the system operates. The techniques will be used to evaluate beat-to-beat baroreflex and respiratory modulation of autonomic function in normal animals and humans. The project will be divided into 2 parts. during Part I, I will gain further specific training by auditing 3 courses at measurement of percutaneous intraneural recordings. Part I. In a chronic animal preparation, cardiac vagal and sympathetic activity will be measured directly to evaluate the baroreflex by its frequency response during broad-band stimulation of arterial pressure with an aortic occluder cuff. This will be done with the blood pressure - heart rate control loop closed, and with it opened by disruption of atrioventricular conduction. Part II. In humans, peroneal nerve muscle sympathetic activity and heart rate will be measured to determine the closed-loop baroreflex frequency response during broad-band stimulation of the carotid baroreceptors with a neck suction chamber. Analysis, of this data will depend critically on the system identification techniques developed to compare open- and closed-loop baroreflex control in Part I. Part III. A clinical research application of the protocol in Part II may begin on subjects with borderline hypertension and subjects with severe stable chronic congestive heart failure.