Summary

In a rat model of lipopolysaccharide (LPS)-induced disseminatedintravascular coagulation (DIC), we used urokinase (UK) in anattempt to clarify the role of fibrinolysis and to investigatechanges in plasma endothelin levels. Two kinds of experimentwere performed.The first one: experimental DIC was inducedby sustained infusion of 30 mg/kg LPS for 4 h via the tail vein, andtwo doses of UK (2.0 or 10.0 IU/g/4.5 h) were administered torats 30 min before infusion of LPS, after which UK infusion wascontinued for a further 4 h. The second one: experimental DICwas induced by sustained infusion of 1 mg/kg/10 min LPS for 10min, and two doses of UK (2.0 or 10.0 IU/g/4 h) were administeredto rats at 30 min after LPS infusion.The parameters describedbelow were determined at 4 h in the first experiment, at4 h and 8 h in the second one.The similar results were observedin both kinds of experiment.There were no significant differencesin plasma thrombin-antithrombin complex, fibrinogen orplatelet number among the three DIC groups, in both kinds ofexperiment. Plasma levels of D-dimer were significantly increased in the LPS + higher dose of UK group when comparedwith the LPS group.The increased plasma plasminogen activatorinhibitor (PAI) activity seen in the LPS group was significantlysuppressed in the groups receiving UK (especially higher dose ofUK). In addition, the increased plasma levels of creatinine and alanineaminotransferase seen in the LPS group were significantlysuppressed in the groups receiving UK (especially higher dose ofUK). Plasma levels of endothelin, known to be a potent vasoconstrictiveagent,were markedly elevated by LPS infusion,and weresignificantly suppressed in the groups receiving UK of both kindsof experiment, in a dose-dependent fashion compared with LPSgroup. Glomerular fibrin deposition was significantly suppressedin the groups receiving UK when compared with the LPS group.No manifestations of bleeding were observed in any of thegroups. Enhanced fibrinolysis and depressed endothelin inducedby UK thus appear to play an important role in preventing thedevelopment of organ failure in the LPS-induced DIC model.