Previous experiments in our laboratory have quantitatively described the cariovascular response to exercise and emotional (i.e., Pavlovian) conditioning in the unanesthetized monkey, boboon and/or dog before and after surgical cardiac denervation and experimental coronary occlusion. The thrust of this research has been to elucidate neural, hormonal and intrinsic mechanisms controlling cardiac inotropism, chronotropism and, most recently, cardiac arrhythmias and coronary vascular resistance, in awake, behariorally controlled subjects. This renewal proposal is composed of 4 inter-related projects, the goals of which are as follows: Project 1 - to quantify the inter-relationship between left ventricular volume, cardiac inotropsim and cardiac output when the heart is suddenly required to increase its work by means of a behavioral conditioning paradigm. The role of the cardiac autonomic nerves vis-a-vis mechanisms intrinsic to the myocardium will be determined using appropriate pharmacologic blocking agents and surgical cardiac denervation; Project 2 - to examine the incidence and control of ventricular arrhythmias observed during classical conditioning conducted at specific times during acute and chronic coronary occlusion; Project 3 - to determine what behavioral and physiological conditions are associated with large and prolonged increases in coronary vascular resistance; to determine the mechanisms controlling the observed changes in resistance; Project 4 - to determine if those animals experiencing particularly large behaviorally conditioned changes in coronary resistance or cardiac arrhythmias have any physiological or behavioral characteristics in common. Each of these projects uses defined behavioral conditioning procedures to address questions of physiological and health-related significance. """"""""Behavioral stress"""""""" including cardiac sudden death, but the exact physiological and behavioral laws and principals which may be involved in producing these pathological states have not been clearly defined. This project should make a significant contribution to achieving a better understanding of these inter-relationships.
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