Beneficial effects of the new calcium antagonist benidipine hydrochloride on myocardial dysfunction following coronary occlusion and reperfusion in anesthetized dogs.
The protective effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1, 4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) on ischemic myocardium was examined comparing with that of nifedipine in anesthetized dogs subjected to a brief (10 min) coronary artery occlusion and reperfusion (2h). Occlusion of left anterior descending coronary artery elicited elevation of ST-segment and T-wave of epicardial ECG in the ischemic area. Regional myocardial contractile force in this area was depressed throughout the reperfusion period as well as during coronary occlusion period. LV max dp/dt, stroke volume and cardiac output tended to be reduced. In the dogs pretreated with 10 micrograms/kg of KW-3049 (i.v.) and 50 micrograms/kg of nifedipine (i.v.), both of which lowered the blood pressure to the same extent, elevation of ST-segment and T-wave was inhibited, and the prevention of irreversible depression of regional myocardial contraction observed at reperfusion periods was slightly more prominent in KW-3049 administration group. Stroke volume and cardiac output in both KW-3049 and nifedipine administration groups were maintained at higher levels than those in control group throughout coronary occlusion and the following reperfusion periods. LV max dp/dt of KW-3049 administration group was kept higher than that of the control group, while the value of the nifedipine administration group changed as that of the control group. These results demonstrate that KW-3049 as well as nifedipine exert protective effects on ischemic myocardium induced by coronary occlusion and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Karasawa
A
A
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kubo
K
K
Shuto
K
K
Oka
T
T
Nakamizo
N
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015425:Myocardial Reperfusion; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects
D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009543:Nifedipine