Comparative Effects of Two Slow Channel Calcium Entry Blockers, FR 34235 and Nifedipine, on True Coronary Collateral Blood Flow

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Abstract
The effect of a new dihydropyridine calcium entry blocker, FR 34235, on coronary collateral blood flow was compared with that of nifedipine in anesthetized dogs following acute ligation of the left anterior descending coronary artery. A special technique was used to separate true coronary collateral blood flow from overlap flow due to interdigitation of normally perfused tissue contained within the ischemic region. During infusion of doses of both agents, which produced nearly equivalent decreases (15–20 mm Hg) in mean arterial pressure, flow was significantly increased in normal myocardium; however, no change in collateral perfusion to ischemic myocardium was observed. When blood pressure was returned to control by an aortic cuff, blood flow to the normal region further increased. Transmural flow to the ischemic region was also significantly increased by both compounds. Nifedipine increased collateral flow primarily to the subepicardium, whereas FR 34235 increased collateral perfusion to the subepicardium, midmyocar-dium, and subendocardium. These results suggest that dihydropyridine calcium entry blockers may increase collateral blood flow to ischemic myocardium if drug-induced hypotension is minimized. In addition, FR 34235 has a more favorable effect on the transmural distribution of blood flow than nifedipine.