BRL 34915 Ameliorates Oxygen Supply in Ischemic Myocardium by a Simultaneous Enhancement of Coronary Blood Flow and a Reduction of Myocardial function

Abstract

In the presence of stenotic coronary arteries, oxygen supply in the poststenotic myocardium is reduced. A counterbalancing poststenotic metabolic vasodilatation is attenuated up to 30% by an .alpha.2-adrenoceptor-mediated vasoconstrictor tone. In six open-chest dogs, we determined whether cumulative intracoronary doses (1, 4, and 14 .mu.g) BRL 34915, a vasodilator with additional dose-dependent cardiodepressant properties, could enhance coronary blood flow and simultaneously reduce myocardial function in poststenotic myocardium, thereby increasing oxygen supply and decreasing oxygen demand. BRL 34915 increased mean left circumflex coronary blood flow [ml/(min .cntdot. 100g)] dose-dependently from 59 .+-. 12.4 (mean .+-. SEM) (no BRL) to 227 .+-. 43.9 (14 .mu.g BRL) (p < 0.05) in intact coronary arteries and from 36 .+-. 7.2 (no BRL) to 74 .+-. 13.2 (14 .mu.g BRL) (p < 0.05) distal to a severe stenosis, respectively. In contrast, posterior systolic wall thickening (%), was significantly decreased only by 14 .mu.g BRL from 9.7 .+-. 1.82 (no BRL) to 7.8 .+-. 2.07 (14 .mu.g BRL) (p < 0.05) when coronary arteries were intact and from 8.7 .+-. 2.02 (no BRL) to 4.1 .+-. 1.39 (14 .mu.g BRL) (p < 0.05) in poststenotic myocardium. We conclude that BRL 34915 can both enhance coronary blood flow in the postentoic myocardium and decrease myocardial function simultaneously, potentially narrowing the gap between oxygen supply and demand.