NEUTROPHIL ELASTASE - A DETERMINANT OF ENDOTHELIAL DAMAGE AND REPERFUSION INJURY AFTER LIVER-TRANSPLANTATION

Reperfusion injury has been implicated in the development of primary g raft dysfunction (PGD) after liver transplantation. Neutrophil migrati on and activation may be involved in the pathogenesis of this injury. We studied neutrophil activation and its role in the etiology of PGD b y measuring neutrophil elastase by radioimmunoassay, in serial blood s amples of 19 patients before, during, and for 24 hr after transplantat ion, In a subgroup of patients, we also measured soluble thrombomoduli n at the same time points as a marker of endothelial damage. The pretr ansplant elastase level was significantly raised (40.13+/-4.84 ng/ml, mean +/- SEM) compared with levels of healthy controls (18.7+/-5.6 ng/ ml, P<0.05), A marked increase in elastase activity followed reperfusi on, with a peak at 2 hr (370+/-50.5 ng/ml, P<0.01). Thereafter, there was a decline, but elastase remained elevated at 24 hr (186+/-60.94 ng /ml), The mean increase in neutrophil elastase after reperfusion corre lated significantly with markers of graft function (P<0.05) and with t he mean rise in soluble thrombomodulin (P=0.042), which increased from a pretransplant level of 81.2+/-11.32 to 186+/-50.4 ng/ml, 6 hr after reperfusion (P<0.05). The results of this study indicate that marked neutrophil activation and endothelial cell damage occurs after graft r eperfusion during orthotopic liver transplantation, and the degree of activation correlates with markers of graft function, which may sugges t a role in the etiology of PGD.