Beneficial actions of amlodipine in the multiple-stunned canine myocardium.
The effects of the long-acting dihydropyridine calcium-entry blocker, amlodipine, on subendocardial segment shortening (%SS), regional myocardial blood flow (radioactive microspheres), and tissue high-energy phosphate levels were compared with those of a saline-treated group of barbital-anesthetized dogs subjected to nine 5-minute coronary artery occlusions interspersed with 15 minutes of reperfusion and finally by 1 hour of reperfusion (multiple stunned myocardium). Saline or amlodipine (200 micrograms/kg, IV) were administered 15 minutes prior to the first coronary occlusion. There were no major differences between groups in ischemic bed size or hemodynamics throughout the experiment. Subendocardial collateral blood flow was significantly increased in the amlodipine-treated group during coronary occlusion 1; however, tissue blood flow in the ischemic region was not significantly different between groups during occlusion 9. Following each occlusion, %SS in the ischemic region was equally reduced in both groups 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 at 15 minutes following each occlusion (1-9) and at 15, 30, and 60 minutes of reperfusion following occlusion 9, as compared to saline-treated animals. In addition, amlodipine attenuated the loss of adenine nucleotides in the ischemic-reperfused area at 1 hour of reperfusion. These results suggest that amlodipine has a favorable effect on the functional and metabolic recovery of the multiple-stunned myocardium and may have potential as a cardioprotective agent for the treatment of myocardial reperfusion injury.
Gross
G J
GJ
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Pieper
G M
GM
D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D004734:Energy Metabolism; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015424:Reperfusion
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine