Protective effects of ulinastatin against ischemia-reperfusion injury

We investigated the protective effect of urinary trypsin inhibitor (ulinast atin: UTI) in vitro, in relation to the neutrophil activity in hepatic isch emia/reperfusion (I/R) injury. The rat liver was removed and preserved in c old Ringer's lactate solution for 60 min, followed by 120 min of reperfusio n with oxygenated perfusate. The rats were divided into four groups (n = 8 in each group). The livers were perfused with Krebs-Henseleit (H-H) solutio n containing no additives in group 1, 50,000 U/kg of UTI in group 2, 3.5 x 10(6) of neutrophils in group 3, and both neutrophils and UTI in group 4. I n group 3, the AST and ALT levels were always higher than those in other th ree groups at any point evaluated (P < 0.01) and the LDH levels were observ ed to be significantly higher than those in other three groups at 0, 5, 10, 60, and 90 min after reperfusion (P < 0.01). These increase were suppresse d by additional pretreatment with UTI in group 4. The bile flow during repe rfusion was significantly suppressed in group 3 compared to that of group 4 , at both 30 (P < 0.01) and 60 (P < 0.05) min after reperfusion. The MPO ac tivity after reperfusion in group 3 also significantly increased compared t o other three groups (P < 0.01). These data thus suggest that UTI ameliorat ed the ischemia/reperfusion injury in vitro by inhibiting of neutrophil acc umulation in the post-ischemic liver. (C) 1999 Academic Press.