Coronary collateral blood flow in acute myocardial ischemia is not increased by dihydropyridine-induced coronary vasodilatation.
The effect of two dihydropyridine derivatives, nifedipine and felodipine, on myocardial blood flow distribution 1 h after ligation of the left anterior descending coronary artery (LAD) was studied in open-chest dogs by means of radioactive microspheres. The myocardium normally perfused from the LAD was first labeled with 125I-labeled microspheres injected directly into the LAD before ligation. Microspheres used for blood flow measurements were given in the left atrium. An intravenous infusion rate of 0.3 nmol/kg/min felodipine slightly depressed mean aortic blood pressure (approximately 5 mm Hg) and decreased coronary vascular resistance in normal myocardium. Nifedipine, at three times the dose of felodipine, had a comparable hypotensive effect, but the decrease in coronary vascular resistance was not statistically significant. The two dihydropyridines were also compared in a dose range that was four times higher. The mean arterial blood pressure reduction (approximately 30% for both drugs) was counterbalanced by inflation of an intraaortic balloon to avoid a drastic decrease in afterload and coronary perfusion pressure. Under these circumstances, felodipine and nifedipine decreased coronary vascular resistance and increased blood flow to nonischemic myocardium comparably. However, in severely ischemic, truly collateral-dependent myocardium without admixture of interdigitating healthy myocardium, the blood flow was unaffected after administration of both felodipine and nifedipine. Although felodipine was three times more potent than nifedipine with regard to vasodilatation in the normal myocardium, the difference in vascular selectivity between the two agents did not influence the effect on the "true" collateral blood flow in acute myocardial ischemia.
P O
PO
Sjöquist
G
G
Duker
O
O
Almgren
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D004095:Dihydropyridines; D004285:Dogs; D004562:Electrocardiography; D015736:Felodipine; D005260:Female; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011725:Pyridines; D014665:Vasodilator Agents; C038806:1,4-dihydropyridine; D009543:Nifedipine; D015736:Felodipine