Protocol I: Activation of the sympathetic nervous system during acute myocardial infarction can be harmful to ischemic myocardium. Propranolol, in contrast to placebo, has been shown to decrease 1-norepinephrine release during acute myocardial infarction, expressed by a decrease in 1-norepinephrine concentration in peripheral blood. Propranolol has also been shown to decrease total coronary blood flow during acute infarction; probably secondary to autoregulation from decreased myocardial oxygen demand in the non-ischemic compartment. The response of coronary blood flow and myocardial metabolism in the ischemic/infarcting compartment following Beta-adrenergic blockade has not been examined in man. This project is designed to study the transcardiac 1-norepinephrine pattern during evolving myocardial infarction and to test the hypothesis that Beta-adrenergic blockade will decrease myocardial sympathetic activiation, reflected by a fall in coronary sinus 1-norepinephrine contents. This project will also investigate compartmental (ischemic/infarcting vs. non-infarcting) coronary blood flow and metabolism and evaluate the response to Beta-adrenergic blockade during evolving myocardial infarction in man. Because interpretation of coronary sinus 1-norepinephrine contents is complex, it is planned to design a series of projects in the animal laboratory. Neurotransmittor release, reuptake, and metabolism will be studied in experimental infarction/ischemia to investigate the different factors determining coronary sinus 1-norepinephrine contents. Protocol II: Most recent studies have shown that patients with congestive cardiomyopathy have decreased resting coronary blood flow per unit mass of left ventricle. Data explaining this finding and its significance are scarse and contradictory. Possible explanations include: 1) decreased contractility reducing metabolic demand; 2) impaired subendocardial blood flow causing subendocardial ischemia; and/or 3) abnormalities of the coronary vascular bed. The proposed study will evaluate coronary blood flow and myocardial metabolism at rest and during pacing-induced stress, and will assess coronary vascular reserve in response to intravenous dipyridamole in patients with idiopathic congestive cardiomyopathy. Endomyocardial biopsies will be done to investigate myocardial pathology in these patients. This study is designed to gain a better understanding of the pathological process in these patients and suggest new therapeutic interventions.
