Effect of efonidipine, a novel dihydropyridine derivative, on myocardial metabolic changes induced by coronary artery ligation in dogs: comparison with nifedipine.
Efonidipine is a dihydropyridine derivative having a vasodilating action, which is slower in onset and longer in duration than that of nifedipine. In the present study, we compared the effects of efonidipine with those of nifedipine on the ischemic myocardial metabolism in anesthetized dogs. The heart was made ischemic by ligating the left anterior descending coronary artery (LAD) completely for 3 or 30 min. Efonidipine or nifedipine was injected intravenously, 10 or 3 min, respectively, before the start of LAD occlusion. Efonidipine (0.01 or 0.03 mg/kg) decreased both blood pressure and heart rate, whereas nifedipine (0.003 mg/kg) decreased blood pressure and increased heart rate. The magnitude of decrease in mean blood pressure induced by 0.03 mg/kg efonidipine was similar to that induced by 0.003 mg/kg nifedipine. Although efonidipine did not modify the changes in myocardial carbohydrate metabolism induced by ischemia, it attenuated the ischemia-induced decrease in the myocardial level of adenosine triphosphate and energy charge potential. Nifedipine, however, did not modify the changes in both myocardial energy and carbohydrate metabolism induced by ischemia. The results suggest that efonidipine has a cardioprotective effect in the dog, probably because of its negative chronotropic effect.
Yokoyama
T
T
Department of Pharmacology, Asahikawa Medical College, Japan.
Ichihara
K
K
Abiko
Y
Y
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D009543:Nifedipine