Endothelial cell dysfunction after ischemic arrest and reperfusion: A possible mechanism of myocardial injury during reflow

To determine the mechanism(s) responsible for decreased coronary flow after global cardiac ischemia and reperfusion, we studied 40 isolated rabbit hearts before and after 30 minutes of normothermic ischemic arrest and reperfusion. In the control group (n = 10) we evaluated the time course of recovery of coronary flow, vascular reactivity, and myocardial function. In experimental groups A (n = 10) and B (n = 10), metabolic control of autoregulation was assessed by plots of myocardial oxygen consumption versus coronary flow generated by incremental increases in heart rate. The slope and intercept of these plots suggested that autoregulation of coronary flow was maintained after ischemia. In group B hearts (n = 10) hyperosmolar reperfusion with mannitol decreased myocardial water by 2% (p < 0.01) but did not increase coronary flow. Endothelium-dependent function was assessed in group C (n = 10) by the administration of an endothelium-dependent vasodilator (serotonin) and a smooth muscle vasodilator (adenosine). Coronary artery smooth muscle function was comparable in hearts before and after ischemia. However, endothelium-dependent increases in coronary flow to serotonin were significantly impaired after ischemia (p < 0.01), and this was accompanied by a significant decrease in prostacyclin synthesis by the endothelium (p < 0.001). Global cardiac ischemia and reperfusion damages coronary artery endothelium, causing increased coronary vasomotor tone; this may be an important mechanism of decreased coronary perfusion and subsequent myocardial injury during reflow.