ISCHEMIC PRECONDITIONING PROTECTS AGAINST CORONARY ENDOTHELIAL DYSFUNCTION INDUCED BY ISCHEMIA AND REPERFUSION

Background Repetitive, brief periods of ischemia and reperfusion (''pr econditioning'') increase the resistance of myocardial tissue to subse quent prolonged ischemic episodes and limit infarct size. We investiga ted whether preconditioning also protects against coronary endothelial dysfunction induced by ischemia and reperfusion. Methods and Results Experiments were performed in four groups of rats (n=8 in each group): group 1 rats underwent sham surgery, group 2 rats were subjected to 2 0 minutes of left coronary artery occlusion without reperfusion, group 3 rats underwent 20 minutes of occlusion followed by 1 hour of reperf usion, and group 4 rats (preconditioning group) underwent the same pro tocol as group 3 rats, preceded by three cycles of 5 minutes of ischem ia and 5 minutes of reperfusion. At the end of the experiments, corona ry segments (internal diameter, 250 to 300 mu m) were removed distal t o the occlusion site and mounted in wire myographs for isometric tensi on recording. Relaxations induced by increasing concentrations of acet ylcholine, the calcium ionophore A23187, or the nitric oxide (NO) dono r SIN-1 were determined in arteries precontracted by serotonin. Basal NO release was estimated by measuring contractions to N-G-nitro L-argi nine methyl ester (L-NAME). In addition, we determined the effect of p reconditioning on infarct size in two additional groups that were subj ected to the same protocols as those of groups 3 and 4. In those anima ls, area at risk (India ink injection) and infarct size (triphenyltetr azolium stain) were determined by computerized analysis of enlarged se ctions after video acquisition. Preconditioning markedly limited infar ct size (percent of area at risk: controls, 57+/-2; preconditioning, 2 .2+/-0.6; P<.01). Ischemia (without or with reperfusion) or preconditi oning did not affect the coronary responses to L-NAME, serotonin, A231 87, or SIN-1. Ischemia without reperfusion did not modify the relaxati ons to acetylcholine (maximal relaxation: sham, 58+/-4%; ischemia, 56/-7%; P=NS). In contrast, ischemia followed by reperfusion markedly im paired the response to acetylcholine (26+/-6%; P<.01 versus sham). Thi s impaired response was restored by preconditioning (maximal relaxatio n: 59+/-9%; P=NS versus sham; P<.01 versus ischemia/reperfusion). Conc lusions In addition to protecting myocardial cells, preconditioning al so protects coronary endothelial cells against ischemia/reperfusion in jury.