Effects of amlodipine on myocardial ischemia-reperfusion injury 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 with 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 administered intravenously) was given 15 minutes before coronary occlusion. There were no significant differences between groups in ischemic bed size or hemodynamics although dP/dt was higher after amlodipine administration. Subepicardial collateral blood flow was higher in the amlodipine group during coronary occlusion. After occlusion, %SS in the ischemic region was markedly decreased in both series and passive systolic lengthening resulted. Despite similar decreases in %SS during occlusion, the amlodipine-treated dogs showed a marked improvement in myocardial segment function of the ischemic reperfused region throughout 60 minutes of reperfusion compared with saline-treated dogs. In addition, amlodipine prevented the rebound increase in phosphocreatine and attenuated the loss of adenine nucleotides and 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 or a decrease in afterload.
Gross
G J
GJ
Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Farber
N E
NE
Pieper
G M
GM
D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D014463:Ultrasonography
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine