Comparative Effects of a New Calcium Antagonist, FR 7534, Nitroglycerin, and Dipyridamole on Regional Myocardial Blood Flow and Cardiac Contractility During Partial Coronary Artery Occlusion in the Dog
The present study was designed to determine the effects of three different types of coronary vasodilators--FR 7534 (a new calcium antagonist), nitroglycerin, and dipyridamole--on the transmural blood flow and contractile function in the normal and ischemic myocardium of anesthetized dogs. Radioactive microspheres (15 muc) and Walton-Brodie strain gauge arches were used to measure tissue blood flow and contractile force, respectively. During 5 min intravenous infusions of nitroglycerin (5 microgram/kg/min) or dipyridamole (50 microgram/kg/min), which produced approximately 20% reductions in mean aortic pressure, blood flow and contractile force in ischemic myocardium decreased significantly. Under similar conditions, FR 7534 (10 microgram/kg/min) produced a significant decrease in ischemic contractile force, but tissue blood flow to the ischemic area did not change. In contrast, when mean aortic pressure was controlled by administration of methoxamine, nitroglycerin produced significant increases in ischemic blood flow (42%) and contractile force (47%), whereas dipyridamole produced significant decreases (41 and 32%, respectively). On the other hand, FR 7534 plus methoxamine produced a significant increase in ischemic blood flow (70%); however, ischemic contractile force did not change. These results demonstrate FR 7534 to affect the oxygen supply-demand balance in ischemic myocardium favorably by maintaining blood flow and depressing contractility during hypotension or by increasing flow during controlled systemic pressure.