THE REGIONAL CIRCULATIONS

This program of research is directed toward the development of techniques to measure regional myocardial blood flow and to apply these methods to the study of patients with coronary atherosclerosis. In this application it is proposed to explore neural and humoral factors which modulate coronary blood flow and which may contribute to the abnormalities of regional myocardial perfusion associated with angina pectoris andmyocardial infarction. Studies in which regional myocardial perfusion is measured along with hormone concentrations in arterial and coronary sinus blood are proposed. The goals are: 1) to explore the role of the cardiac prostaglandins and of the sympathetic nerves in the control of coronary flow and in the flow abnormalaities associated with coronary atherosclerosis, 2) to investigate the role of vasodilator prostaglandins in the maintenance of myocardial perfusion in animals and in man during adrenergic stimulation of the heart, 3) to study proteins released from platelets and thromboxane A2 in angina pectoris, 4) to investigate these factors inpatients with atherosclerosis and residual myocardial infarction, and 5) to study the role of prostaglandin synthesis during the hyperemia of coronary reperfusion. In collaboration with investigators at the Brookhaven National Laboratory, it is proposed: 1) to develop a new non-invasive method to measure regional myocardial blood flow using 18F-antipyrine and positron emission transaxial tomography (PETT), 2) to study myocardial catecholamine storage and turnover in intact animals with myocardial ischemia and with congestive heart failure using 11C-norepinephrine and PETT, 3) to explore the properties of a new Beta adrenergic blocking agent, iodocyanopindolol (I-CYP), as a potential probe of the myocardial Beta adrenergic receptor, and 4) to attempt, using 18F-CVP and PETT, to develop a method to assess the number and function of the myocardial Beta adrenergic receptors in intact animals.