Effects of FUT-175, a New Synthetic Protease Inhibitor on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

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Abstract
The effects of FUT-175 (6-amidino-2-naphthyl-4-guanidino benzoate-dimethanesulfonate), a new synthetic protease inhibitor, on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4-hour sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were infused continuously with FUT-175 at 0.001, 0.01, 0.1, 1.0 or 10.0 mg/kg into a femoral vein for 4 h. Simultaneously with the agent infusion, endotoxin (100 mg/kg/4 h) was administered into the contralateral femoral vein. A protective effect against DIC was noted in the rats treated with 0.01 or 0.1 mg/kg of FUT-175 in the following parameters: fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi. These results demonstrated that FUT-175 reduces the extent of changes of the coagulation parameters caused by DIC.