This application is designed to examine the role of the central nervous system in regulating coronary blood flow. Specific central sites important for systemic blood flow regulation (rostroventrolateral medulla, Area Postrema, and certain nuclei in the Av3v region) will be examined for their influence on coronary flow. Using retrograde tracers, the origins of these central coronary pathways will be defined and likewise stimulated. It is anticipated that from certain of these more proximal regions selective coronary responses may be elicited. Identification of putative coronary vasomotor areas and their central connections would be important to our understanding of neural coronary control mechanisms. To determine the sites and mechanisms of coronary regulation, responses to electrical stimulation in the specific central vasomotor areas mentioned above will be examined. Doppler coronary and femoral flow changes to unipolar electrical stimulation will be measured in anesthetized cats. These data together with preliminary data from our laboratory demonstrating other central coronary vasomotor areas (lateral reticular formation of the medulla, lateral hypothalamus, and paraventricular nucleus) will be used to direct neural tracer injections for defining the sites of origin of the coronary responses. Electrical stimulation in these more proximal areas should broaden our understanding of central pathways mediating neural coronary vasoconstriction. We will examine the contribution of neurohumoral components to the coronary constrictor response by using specific adrenoreceptor antagonists, stellectomy, and adrenalectomy. Further characterizatiion of coronary flow changes to central stimulation will involve measurement of transmural myocardial perfusion and studies in an awake instrumented preparation devoid of the neural and vasomotor inhibitory effects of general anesthesia. By identifying those central nervous system areas involved in coronary flow regulation, we hope to gather new information concerning neural coronary control. The results of these experiments will have important clinical ramifications since the sympathetic nervous system has been implicated as an important etiologic factor in coronary artery spasm, angina pectoris, and myocardial infarction.
