Beneficial effect of nafamostat mesilate on tissue-factor-induced DIC models, especially on hemostatic markers and vasoactive substances, in rats

Abstract

We have previously reported that an increase in plasma level of NOX, a metabolite of nitric oxide(NO), was marked but that of endothelin remained rather slight in the tissue factor(TF)-induced DIC models in rats, and that these findings appeared to be characteristic in the TF-induced animal DIC models. In this study, we have investigated whether nafamostat mesilate (FUT) was able to affect and modify the pathophysiology of DIC in these animal models. DIC was induced in the Wistar strain male rats by administering TF at 3.75units/kg of body weight via their tail vein over a period of 4 hours. The effect of FUT on the TF-induced DIC was observed by continuous administration of FUT, either at 0.1 mg/kg or 1.0 mg/kg, which had been started 30 minutes prior to the TF administration. The decreased platelet counts and plasma fibrinogen and the increased thrombin-antithrombin complex and the D-dimer, which had been generally noted in these animal models, were all considerably reduced. Appearance of hematuria frequently observed in these animal models was also markedly reduced. Furthermore, the increase of NOX was nearly completely suppressed. From these results, we conclude that FUT was able to reduce the bleeding tendency and to inhibit the enhancement of fibrinolysis in the TF-induced DIC models in rats. Further studies are required to clarify the mechanism of effective inhibition by FUT of these reations including the increase of NO production widely noted in the DIC models in rats.