Alteration of endothelium-dependent distribution of myocardial blood flow after coronary occlusion and reperfusion

We have previously demonstrated that intracoronary infusion of the endothelium-dependent vasodilators acetylcholine, ATP, or arachidonic acid produces a preferential increase in subendocardial blood flow in anesthetized dogs. This study was performed to assess the effects of coronary artery occlusion and reperfusion on the distribution of myocardial blood flow produced by endothelium-dependent and endothelium-independent vasodilators. The endothelium was damaged by occlusion of the left anterior descending coronary artery for 45 minutes followed by 60 minutes of reperfusion in pentobarbital-anesthetized dogs. Intracoronary infusions of the endothelium-dependent vasodilators acetylcholine, bradykinin and thiazolylethylamine or the endothelium-independent vasodilator sodium nitroprusside were performed, and regional myocardial blood flow (by radioactive microspheres) was measured before and after occlusion and reperfusion. There were no changes in systemic hemodynamics during intracoronary infusion of vasodilators before or after coronary occlusion and reperfusion. All vasodilators produced similar increases in transmural blood flow before occlusion; however, only the endothelium-dependent vasodilators produced a significant increase in the subendocardial-to-subepicardial blood flow ratio. Increases in transmural flow as well as the preferential increase in subendocardial blood flow produced by acetylcholine, bradykinin, and thiazolylethylamine were attenuated after coronary occlusion and reperfusion. In contrast, increases in transmural blood flow produced by sodium nitroprusside were unchanged. These results suggest that the preferential increase in subendocardial perfusion produced by acetylcholine, bradykinin, and thiazolylethylamine is endothelium-dependent and may be selectively modified by ischemic insult.