Effects of nicardipine, a dihydropyridine calcium antagonist, on regional myocardial blood flow, myocardial oxygen tension, and electrical abnormalities during acute coronary artery occlusion in dogs.
Effects of nicardipine, a dihydropyridine calcium antagonist, on regional myocardial blood flow (RMBF), myocardial oxygen tension (PO2), and excitation and conduction abnormalities during the occlusion of the left anterior descending coronary artery (LAD) were examined in anesthetized dogs, and compared with those of nifedipine and dipyridamole. RMBF was calculated from the H2 gas clearance curves, and PO2 was measured using a membrane-coated Pt wire. Excitation and conduction abnormalities during the LAD occlusion were represented in terms of the degree of ST-T alternans (STTA), TQ depression, and conduction delay, which appeared in epicardial electrograms. Nicardipine and nifedipine in a dose of 10 micrograms/kg increased RMBF and PO2 levels in nonischemic and mildly ischemic tissues, but not in severely ischemic tissues. Nicardipine in a dose of 100 micrograms/kg and nifedipine in a dose of 10 micrograms/kg attenuated the degree of STTA, TQ depression, and conduction delay observed in severely ischemic tissues. In mildly ischemic tissues where only TQ depression was observed without STTA, nicardipine in a dose of 30 micrograms/kg attenuated TQ depression. Dipyridamole in a dose of 1 mg/kg produced only a slight attenuation of STTA and conduction delay. These results suggest that the beneficial effects of nicardipine as well as of nifedipine on myocardial ischemia are due to the increase in the myocardial PO2 levels caused by the increased RMBF and also to direct protecting effects on ischemic myocardial cells. In the severely ischemic tissues, the latter is a main effect of the drugs. In increasing the PO2 level, nicardipine was similarly potent as nifedipine, but in the direct effect, nicardipine was less potent, and dipyridamole was almost ineffective.
Hashimoto
H
H
Asano
M
M
Takiguchi
Y
Y
Katoh
H
H
Nakashima
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004176:Dipyridamole / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D013997:Time Factors
D002121:Calcium Channel Blockers; D004176:Dipyridamole; D009529:Nicardipine; D009543:Nifedipine