DELAYED ENHANCED NITRIC OXIDE-MEDIATED CORONARY VASODILATION FOLLOWING BRIEF ISCHEMIA AND PROLONGED REPERFUSION IN CONSCIOUS DOGS

The goal of this study was to determine both the early and delayed eff ects of a brief (10-minute) coronary artery occlusion (CAO) and prolon ged (5-day) reperfusion (CAR) on coronary endothelial function. Fourte en mongrel dogs were chronically instrumented to measure aortic and le ft ventricular pressures, wall thickness, and left circumflex coronary blood flow (CBF). Before CAO and during CAR, coronary vascular reacti vity was investigated by 15-second CAO and subsequent reactive hyperem ia (RH) and by the selective intracoronary infusion of acetylcholine ( ACh, 10 mu g/min) and bradykinin (BK, 2.5 mu g/min), endothelium-depen dent vasodilators, and sodium nitroprusside (SNP, 40 mu g/min), an end othelium-independent vasodilator. CBF responses to ACh and BK began to increase after 6 hours of CAR, reached a peak after 1 to 2 days of CA R, and then subsided over the subsequent 4 days. After 1 day of CAR, c ompared with before CAO, enhanced CBF responses (P<.05), associated wi th increased coronary sinus oxygen content, were observed for ACh (+66 +/-20%), BK (+74+/-24%), and RH (+24+/-5%) but not SNP (-2+/-10%). Pro duction of NO metabolites (nitrate and nitrite), measured as their cor onary arteriovenous difference x CBF, was significantly increased afte r 1 to 2 days of CAR, both at baseline (153+/-56%) and during BK infus ion (220+/-76%) (P<.05). Holding CBF at pre-CAO levels during the init ial CAR period did not attenuate the delayed enhanced endothelial vaso dilation to ACh and BK. However, NO blockade with intracoronary N-G-ni tro-L-arginine blocked the enhanced coronary vasodilation to ACh and B K. Thus, in contrast to previous studies, these data indicate that bri ef ischemic episodes induce delayed enhanced coronary endothelial func tion, which is delayed in onset and prolonged in duration. This can be explained by an upregulation of coronary vascular NO production, pote ntially involved in the mechanism of the delayed window of preconditio ning.