Endothelial function following ischemia.

The consequences of ischemia and reperfusion on endothelial dependent and independent coronary flow patterns following a variety of ischemic insults in isolated perfused rabbit hearts were studied. A blood perfused ex vivo model was developed that provided reliable and stable systolic performance comparable to crystalloid perfused hearts, but with a four to sevenfold decrease in resting coronary flow and a three to six fold increase in coronary flow reserve compared to Krebs' perfusion. Following incremental graded 37 degrees C ischemia of 10 to 45 minutes, blood perfused hearts had compromised systolic performance, but unaffected response to exogenous endothelial dependent and independent agonists whereas in crystalloid perfused hearts, the response to these same agonists was blunted prior to noting a decrement in systolic function. Further studies assessed the consequences of 30 and 45 minutes of ischemia on the regulatory role of basal nitric oxide released by the coronary endothelium. In both blood and crystalloid perfused hearts, basal nitric oxide secretion had a significant and persistent regulatory role on coronary vascular tonus over a tenfold range of coronary flow despite ischemic injury that severely depressed systolic performance. Finally, hearts were preserved in University of Wisconsin (UW) or St. Thomas' (ST) solutions for 4 hours at 4 degrees C. With crystalloid perfusion, ST results in impaired postischemic response to both endothelial dependent and independent agonists. After UW preservation and with all blood perfused hearts, postischemic flow patterns were unchanged. Using physiological blood perfusion protocols, the endothelium and arterial smooth muscle were found more resistant to ischemia-reperfusion injury than the myocyte.