Reduction of Myocardial Infarct Size by the Calcium Antagonist FR 7534

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Abstract
The effect of FR 7534 [1,4-dihydro-2-hydroxymethyl-4-(m-nitrophenyl)-6-methyl-3,5-pyridine dicarboxylic acid diethyl ester], a light-stable derivative of nifedipine on hemodynamics, coronary collateral blood flow and myocardial infarct size was studied in the anesthetized dog. Myocardial infarction was produced by a 2-h occlusion and reperfusion of the distal third of the left anterior descending coronary artery in control dogs, FR 7534-treated dogs and FR 7534-treated dogs with a constant aortic blood pressure. FR 7534 alone produced significant decreases in heart rate and mean aortic blood pressure. No change in collateral blood flow of central ischemic zones was observed. When aortic blood pressure was held constant, FR 7534 produced a significant increase in coronary collateral blood flow. With or without a constant aortic perfusion pressure, FR 7534 significantly reduced infarct size as compared to control experiments (33.5 to 4.3 and 7.5% of the area at risk infarcted, respectively). The efficacy of a new Ca antagonist, FR 7534, to protect ischemic myocardium with or without a change in O2 supply via the coronary collateral circulation is demonstrated.