Comparison of two dihydropyridine calcium antagonists on coronary collateral blood flow in acute myocardial ischemia.
Effects of two dihydropyridine calcium antagonists on regional myocardial blood flow produced by acute ligation of the left anterior descending coronary artery were examined in the pentobarbital-anesthetized open-chest dog. Equivalent hypotensive doses of nifedipine (1.25 and 2.5 microgram/kg/min) and FR 7534 (5 and 10 micrograms/kg/min) produced similar decreases in mean arterial pressure and myocardial oxygen consumption and increases in coronary blood flow, dp/dt and contractile force in the intact nonischemic dog heart. Heart rate was unaffected. Nifedipine was 4 times as potent as FR 7534. Effects on ischemic myocardial blood flow measured with radioactive microspheres were examined with the same doses and also at controlled mean arterial pressure by use of methoxamine. Despite significant hypotension, nifedipine maintained and FR 7534 increased ischemic blood flow. When perfusion pressure was controlled, both compounds produced significant increases in transmural blood flow to the ischemic region. The increase produced by FR 7534 was significantly greater. Both nifedipine and, to a lesser extent, FR 7534 decreased the subendocardial to subepicardial blood flow ratio in the nonischemic myocardium without altering that of the ischemic myocardium. Drug-induced increases in ischemic blood flow were positively correlated with initial flow rate. The results indicate that both dihydropyridine calcium antagonists are capable of improving the oxygen supply-demand relationship during ischemia by reducing overall myocardial oxygen demand by increasing collateral blood flow.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D003097:Collateral Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*
D011725:Pyridines; C019137:FR 7534; D009543:Nifedipine; D002118:Calcium