Effect of amlodipine on myocardial functional and metabolic recovery following coronary occlusion and reperfusion in dogs.
The effects of the dihydropyridine calcium-channel 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 saline-treated group of barbital-anesthetized dogs subjected to a 45-minute coronary artery occlusion followed by 60 minutes of reperfusion. Saline or amlodipine (200 micrograms/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 nucleotides 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.
Gross
G J
GJ
Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Farber
N E
NE
Pieper
G M
GM
D000227:Adenine Nucleotides / Q000378:metabolism; D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D014867:Water / Q000378:metabolism
D000227:Adenine Nucleotides; D002121:Calcium Channel Blockers; D010710:Phosphates; D010725:Phosphocreatine; D014867:Water; D017311:Amlodipine; D009543:Nifedipine