E-selectin in the pathogenesis of experimental myocardial ischemia-reperfusion injury.

The role of E-selectin in the pathogenesis of an experimental model of myocardial ischemia-reperfusion injury was investigated. Pentobarbital anesthetized rats underwent left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham operated rats were used as controls (sham MI/R). Myocardial ischemia-reperfusion injury reduced survival rate (50%), caused severe myocardial damage (necrotic area/area-at-risk 69.8 +/- 5%; necrotic area/total area = 56 +/- 7.6%), increased serum creatine phosphokinase activity (sham MI/R = 33 +/- 3 U/ml; MI/R = 215 +/- 13 U/ml), and elevated myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation; sham MI/R = 0.11 +/- 0.02 U x 10(-3)/g tissue) in the area-at-risk (7.5 +/- 1.7 U x 10(-3)/g tissue) and in the necrotic area (7.8 +/- 2.2 U x 10(-3)/g tissue). Furthermore, MI/R rats had an increased pressure rate index, studied as a quantitative means for assessing myocardial oxygen demand. Administration of a hyperimmune serum containing antibodies against E-selectin significantly improved survival rate (80%), reduced myocardial injury (necrotic area/area-at-risk = 26.4 +/- 7%, P < 0.005; necrotic area/total area 19.1 +/- 2.8%, P < 0.005), lowered serum creatine phospokinase activity (85 +/- 5 U/ml, P < 0.001) and decreased myeloperoxidase activity in the area at risk (3.7 +/- 1.3 U x 10(-3)/g tissue, P < 0.001) and in the necrotic area (3.0 +/- 0.7 U x 10(-3)/g tissue). Finally, the administration of anti E-selectin antibodies improved the PRI in MI/R rats. The present data suggest that E-selectin in vivo plays a key role in the pathogenesis of myocardial ischemia/reperfusion injury.