Effects of repeated brief episodes of ischemia and reperfusion in isolatedperfused rat hearts

The effects of ischemia and reperfusion on the coronary endothelium and myo cardium as well as tolerance to ischemia/reperfusion injury were assessed u sing isolated retrogradely perfused rat hearts. Repeated brief episodes of myocardial ischemia followed by reperfusion is known to have a protective e ffect against subsequent myocardial infarction. However, no studies have be en performed with perfusion in the absence of blood cells to determine the effect of repeated ischemia and reperfusion on the coronary endothelium and myocardium. Using the Langendorff perfusion technique, rat hearts were sub jected to a 30-, 10-, 5-, or 2-min period of low-flow perfusion by reducing the coronary flow to 3 ml/min followed by reperfusion at 20 ml/min for the same period of time. Control perfusion was then performed at a constant fl ow rate of 20 ml/min for 60 min. Acetylcholine-induced coronary vasodilatio n was significantly (P < 0.05) lower in hearts subjected to 30 min of ische mia and 30 min of reperfusion when compared with the control hearts. Myocar dial creatinine kinase (CK) activity was significantly reduced (P < 0.01) i n hearts subjected to ischemia and reperfusion for either 30, 10, or 5 min. To assess the effect of repeated episodes of ischemia and reperfusion, the following protocols were used: a control study with constant perfusion for 60 min (group A), 30 min of ischemia and 30 min of reperfusion (group B), three 10-min episodes of ischemia and reperfusion (group C), six 5-min epis odes of ischemia and reperfusion (group D), and 15 2-min episodes of ischem ia and reperfusion (group E). Acetylcholine-induced coronary vasodilation w as significantly inhibited in group B (80% +/- 12%, P < 0.05) and group C ( 70% +/- 13%, P < 0.01), but did not change significantly in either group D (123% +/- 19%) or group E (142% +/- 15%), compared with the control group ( group A, 127% +/- 15%, mean +/- SEM). Nitroglycerin-induced coronary vasodi lation was not altered by ischemia/reperfusion ill any group. In contrast, myocardial CK activity was significantly lower in group B (3.6 +/- 0.6 IU/m g protein, P < 0.01), group C (3.2 +/- 0.1 IU/mg protein, P < 0.01), and gr oup D (3.3 +/- 0.2 IU/mg protein, P < 0.01) than in group A (47 +/- 6.7 IU/ mg protein). The myocardial CK activity of group E was not significantly di fferent from that of group A, but was significantly higher than in groups B , C, and D (P < 0.01). In isolated perfused rat hearts, both the coronary e ndothelium and myocardium are damaged by repeated episodes of ischemia and reperfusion. However, the coronary endothelium is more resistant to such da mage than is the myocardium.