Effect of amlodipine on myocardial functional and metabolic recovery following coronary occlusion and reperfusion in dogs

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Abstract
The effects of the dihydropyridine calciumchannel blocker, amlodipine, on subendocardial segment shortening (%SS), regional myocardial blood flow, myocardial high-energy phosphate levels and tissue water content were compared to those of a salinetreated group of barbital-anesthetized dogs subjected to a 45-minute coronary artery occlusion followed by 60 minutes of reperfusion. Saline or amlodipine (200 μg/kg, IV) were administered 15 minutes prior to coronary occlusion. There were no significant differences between groups in ischemic bed size or hemodynamics, although dP/dt was higher following amlodipine. Subepicardial collateral blood flow was higher in the amlodipine group during coronary occlusion. Following occlusion, %SS in the ischemic region was markedly decreased in both series and passive systolic lengthening resulted. In spite of similar decreases in %SS during occlusion, the amlodipine- treated dogs showed a marked improvement in myocardial segment function (%SS) of the ischemic-reperfused region throughout 60 minutes of reperfusion as compared to saline-treated animals. In addition, amlodipine prevented the rebound increase in phosphocreatine and attenuated the loss of adenine nucloetides and the increase in tissue water in the ischemic- reperfused area at 60 minutes of reperfusion. These results suggest that amlodipine has a favorable effect on the functional and metabolic recovery of the ischemic-reperfused myocardium, and may have potential as a therapeutic agent for the treatment of coronary artery disease. The mechanism of action of amlodipine in this model is unknown but may be partially related to a drug-induced increase in coronary collateral blood flow.