Improvement in ischemic myocardial blood flow following a new calcium antagonist

Abstract

The effect of FR 7534, a new dihydropyridine CA2+ antagonist, nitroglycerin, and dipyridamole have been compared on coronary collateral function in pentobarbital-anesthetized open-chest dogs following acute ligation of the left anterior descending coronary artery. Measurements of tissue blood flow using radioactive microspheres were made 60 min postligation after low and high doses of each drug and at the higher dose with methoxamine added to to return mean aortic pressure. FR 7534 treatment increased subepicardial, subendocardial, and transmural tissue flow by 100% in the central ischemic zone when perfusion pressure was controlled by methoxamine. Nitroglycerin also increased ischemic tissue flow, but to a lesser degree, 18% transmurally. Dipyridamole produced no significant change. Tissue flow in normal myocardium was similarly increased by FR 7534 and dipyridamole but slightly reduced by nitroglycerin. FR 7534 and nitroglycerin also increased retrograde coronary pressure when aortic presure was maintained constant. FR 7534, but not nitroglycerin, increased ischemic contractile force. In this model, FR 7534 may produce greater effects than nitroglycerin in increasing blood supply to ischemic myocardium delivered by endogenous collaterals especially when aortic perfusion pressure was controlled.