Effects of FUT-175, a new synthetic protease inhibitor on endotoxin-induced disseminated intravascular coagulation in rats.
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.
D000818:Animals; D001550:Benzamidines; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000517:prevention & control*; D004731:Endotoxins; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000502:physiology; D005340:Fibrinogen / Q000032:analysis; D006146:Guanidines / Q000627:therapeutic use*; D006400:Hematocrit; D007678:Kidney Glomerulus / Q000473:pathology; D010976:Platelet Count; D011517:Prothrombin Time; D051381:Rats; D011919:Rats, Inbred Strains
D001550:Benzamidines; D004731:Endotoxins; D005338:Fibrin Fibrinogen Degradation Products; D006146:Guanidines; D005340:Fibrinogen; C032855:nafamostat