This application investigates the nervous control of cardiac and coronary vascular function in the intact animal. It utilizes exercise and classical aversive or appetitive conditioning to produce controlled, repetitive patterns of change in cardiac sympathetic and parasympathetic nervous activity. The effects of these changes in nervous activity on myocardial contraction, sino-atrial (SA) and atrio-ventricular (AV) nodal function are investigated in 4 inter-related projects as follows: Project 1 seeks to determine (a) if the Alpha-adrenergic vasoconstrictor tone known to persist during exercise or (b) the increase in coronary vascular resistance known to occur during classical aversive conditioning, repress myocardial segmental shortening. It specifically examines contraction in muscle rendered acutely ischemic during exercise or conditioning by stenosis of the left circumflex (LCx) coronary artery. The questions are addressed using infusion of Alpha-adrenergic antagonists and agonists directly into the LCx artery via a chronically indwelling catheter. Projects 2 and 3 examine the roles of the cardiac sympathetic and parasympathetic nerves in controlling sino-atrial and atrio-ventricular nodal function. Both projects use (a) classical appetitive conditioning to produce characteristic changes in autonomic nervous activity and (b) very recently developed surgical procedures for denervating the parasympathetic nerves to the SA or AV nodes; the sympathetic nerves are left intact. This, together with the use of pharmacological blocking agents, will permit us to evaluate the nervous control of cardiac chronotropism and dromotropism more critically than has been heretofore possible. In addition, we will be able to describe quantitatively the effects of an "autonomic imbalance" at either node upon cardiac function. Project 4 harvests data from Projects 1-3, plus several additional experiments; it applies digital signal processing techniques to these data to determine the frequency content of the cardiovascular responses to exercise and behavioral conditioning. The procedures include spectral analysis of cardiovascular variables recorded from resting subjects as well as a systems analysis of responses to provocative behavioral tests in order to shed new insight into the autonomic nervous control of the heart. All 4 projects seek to analyze more critically and effectively the autonomic nervous control of specific aspects of cardiac function in the awake animal.
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NIH ExPorter