Heart rate varies continuously in response to fluctuations of cardiac autonomic activity. In recent years, abnormalities of heart rate control have been associated with a variety of pathophysiologic states. Although interest and experimentation in this field have grown rapidly, the physiologic role of beat-to-beat changes in heart rate as a modulator of cardiovascular hemodynamics has not been critically examined. To integrate the disciplines of regulatory cardiac physiology and ventricular mechanics, systematic investigation of the relations between transient changes in heart rate and ventricular and vascular function is necessary. The results of such investigations will yield significant new insights into the often-associated pathophysiology of disordered heart rate control and ventricular function. In this application, a program of training and a series of experiments in animals and humans is proposed to address these questions. In the first phase of experimentation, a combination of established methodologies for the study of ventricular function and novel signal processing techniques will be used in acute and chronic animal models. A set of parameters will be established which describe:) the effect of beat-to-beat changes in heart rate on independent measures of ventricular preload, afterload and contractility under a variety of physiologic conditions, and 2) how resultant changes in cardiac output effect changes in blood pressure. In spontaneously breathing chronic models, this study will be extended to include an examination of the relations between intrathoracic pressure and volume and ventricular loading conditions, and their interplay with respiratory sinus arrhythmia. In the second phase of experimentation, the investigator will utilize the results obtained in acute surgical and spontaneously breathing chronic animals to normal humans, using established noninvasive echocardiographic techniques to measure load- independent indices of ventricular mechanics. Data obtained in these final studies will be used to guide to the development of a series of protocols for the study of cardiac pathophysiology in a poorly-understood group of emerging clinical importance-patients with palliated congenital heart disease.
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