[Effects of efonidipine hydrochloride, a calcium antagonist derived from dihydropyridine, on acute myocardial ischemia in anesthetized open-chest dogs].
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.
Yokoyama
T
T
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd., Saitama, Japan.
Fujikura
N
N
Masuda
Y
Y
Shikada
K
K
Tanaka
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002302:Cardiac Output / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine