E-SELECTIN IN THE PATHOGENESIS OF EXPERIMENTAL MYOCARDIAL ISCHEMIA-REPERFUSION INJURY

The role of E-section in the pathogenesis of an experimental 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+/-3U/ml;MI/R=215+/-13U/ml), and elevated myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation; sham MI/R=0.11+/-0.02Ux10(-3)/g tissue) in the area-at-risk(7.5+/-1.7Ux10(-3)/g tissue) and in the necrotic area(7.8+/-2.2Ux10(-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), lowered serum creatine phospokinase activity (85+/-5U/ml, P<0.001) and decreased myeloperoxidase activity in the area at risk (3.7+/-1.3Ux10(-3)/g tissue, P<0.001) and the necrotic area (3.0+0.7Ux10(-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.