Perioperative elastase activity in cardiac surgery and its role in endothelial leakage

The functional activity and pathophysiological effects of polymorphonuclear elastase (PMNE) in cardiac surgery patients are unknown. This in vitro study was done to evaluate whether PMNE activity in patient blood samples may be correlated with decreased endothelial wall integrity. PMNE was serially analyzed by PMNE activity in plasma samples from 40 high risk cardiac surgery patients. Endothelial cell cultures were used to study the influence of patient serum on the intercellular integrity. Ex vivo, samples with high PMNE activity (>1.0 mg/ ml), found in 14 patients (35%), neither induced hyperpermeability in cultured endothelial cells nor resulted in intracellular redistribution of the junction molecules cadherin-5 or beta-catenin. However, pretreatment of endothelial cells with these samples but not with low activity (20-fold) in conjunction with formation of intercellular gaps and irregular membrane-associated beta-catenin staining. Neutrophil transmigration was inhibited by blocking neutrophil beta1 integrin but not by the proteinase inhibitor methoxysuccinyl-Ala-Ala-Pro-Ala. Augmented PMNE activity in cardiac surgery patients does not directly induce endothelial leakage but may indirectly promote neutrophil extravasation and thus perioperative endothelial hyperpermeability.