nitrophenols and Myocardial-Ischemia

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.

Topics: Animals; Calcium Channel Blockers; Carbohydrate Metabolism; Dihydropyridines; Dogs; Energy Metabolism; Female; Hemodynamics; Male; Myocardial Ischemia; Myocardium; Nifedipine; Nitrophenols; Organophosphorus Compounds

Effects of efonidipine hydrochloride (NZ-105), a dihydropyridine calcium antagonist, on the cardiovascular system were studied in dogs, in which the left anterior descending coronary artery (LAD) was ligated for 50 min. NZ-105 (10 or 30 micrograms/kg), nifedipine (NIF, 1 or 3 micrograms/kg) or nisoldipine (NIS, 1 or 3 micrograms/kg) was injected i.v. before LAD ligation. NZ-105, NIS or NIF decreased the total peripheral resistance (TPR) and blood pressure (BP) and increased the cardiac output (CO) and regional myocardial blood flow (RBF) dose-dependently. LAD ligation decreased RBF and produced segmental bulging in the ischemic area, decreased BP and CO, and did not change TPR. NZ-105, NIF or NIS attenuated the LAD ligation-induced regional myocardial changes. During LAD ligation, in the presence of NZ-105 (30 micrograms/kg), the values of heart rate (HR), BP, and TPR were lower, and that of CO was higher than those in the absence of the drug. Similar results were obtained with NIS (3 micrograms/kg) except that the value of HR in the presence of NIS was not lower. During ischemia, the presence of NIF (3 micrograms/kg), did not significantly change the values of the systemic circulation from those observed in the absence of NIF. In conclusion, NZ-105 may exert a cardioprotective effect by decreasing the oxygen demand of the ischemic heart.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Cardiac Output; Dihydropyridines; Dogs; Female; Hemodynamics; Male; Myocardial Ischemia; Nitrophenols; Organophosphorus Compounds; Oxygen Consumption; Regional Blood Flow; Vascular Resistance