NITROGLYCERIN AND DIPYRIDAMOLE ON CARDIAC METABOLISM AND DYNAMICS IN A NEW EXPERIMENTAL MODEL OF ANGINA-PECTORIS

Abstract

An experimental model of angina pectoris was developed in order to study the hemodynamic, metabolic and electrophysiological alterations of the heart assumed to occur in the human disease and to analyze the influence of nitroglycerin and dipyridamole on the above changes. In anesthetized and thoracotomized dogs the left anterior descending coronary artery was autoperfused from the subclavian artery. Coronary blood flow was reduced until the epicardial monopolor ECG recorded from the myocardial segment supplied by the constricted coronary artery was just short of ischemic changes. O2 consumption and lactate uptake of the same segment were determined from the arteriovenous difference by sampling venous blood draining this area. Increasing heart rate by 50 to 70 beats/min by electrical pacing of the right atrium evoked a reversible and reproducible elevation of the ST segment and T wave of the ECG. Blood flow to the area perfused by the constricted coronary artery as well as the O2 uptake of the same area failed to increase on pacing. A concomitant decrease of lactate uptake, sometimes becoming even negative, was indicative of ischemia of that area. These changes could be reduced or prevented by a 10-minute infusion of a total dose of 20 .mu.g/kg of nitroglycerin but not by 60 .mu.g/kg of dipyridamole. Since the changes are fully reversible and readily reproducible, and the response also appears to show parallelisms with those observed in the human patient during an acute angina pectoris attack, use of this model for the assay of antianginal drugs seems to be warranted.