Effects of brief coronary occlusion and reperfusion on porcine coronary artery reactivity

Abstract

The loss of coronary vasodilator reserve after ischemia-reperfusion may be due to endothelial injury, and this vascular dysfunction may contribute to functional alterations observed after ischemia. To determine whether endothelial dysfunction occurs after relatively brief periods of moderate low-flow ischemia in vivo, open-chest swine were subjected to 15 minutes of critical, subtotal left anterior descending coronary artery occlusion (80%) followed by 60 minutes of reperfusion. Serial measurements of regional coronary flow were made with the radiolabeled microsphere technique. After 60 minutes of reperfusion, the left anterior descending coronary artery was excised together with a section of the normally perfused left circumflex coronary artery to examine in vitro the relaxations to the endothelium-dependent dilators ADP and bradykinin and to the endothelial-independent dilators sodium nitroprusside and adenosine. Contractions to serotonin in quiescent rings were also examined. Endocardial and transmural blood flows recovered to preocclusion levels within 60 minutes of reperfusion, as did the epicardial-toendocardial ratio. Vascular responses in isolated, reperfused left anterior descending coronary artery rings were significantly different from responses in control left circumflex coronary artery rings. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin were significantly depressed in the left anterior descending coronary artery rings compared with left circumflex coronary artery rings (p<0.05). Serotonin-induced contractions were significantly greater in occluded-reperfused left anterior descending than in left circumflex coronary arteries (p<0.05). Relaxations to adenosine and sodium nitroprusside were not significantly different between the two groups. These data indicate that very brief periods of subtotal coronary occlusion in vivo can induce significant endothelial dysfunction. Although this was not associated with depressed recovery of coronary flow on reperfusion, this abnormality may play a role in postischemic myocardial dysfunction.