Protective effects of ONO-3307, a new synthetic protease inhibitor against experimental disseminated intravascular coagulation in rats

Thromb Res. 1990 Oct 1;60(1):1-7. doi: 10.1016/0049-3848(90)90334-9.

Abstract

The effects of ONO-3307 (4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate), a new synthetic protease inhibitor, on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were infused continuously with ONO-3307 at a dose of 1, 10 or 100 micrograms/kg/h into a femoral vein for 4 h. Simultaneously with the agent infusion, endotoxin (100 mg/kg/4h) was administered into the contralateral femoral vein. A protective effect against DIC was noted in the rats treated with 10 or 100 micrograms/kg/h of ONO-3307 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. Therefore, ONO-3307 inhibited the aggravation of endotoxin-induced experimental DIC in rats.

MeSH terms

  • Animals
  • Disseminated Intravascular Coagulation / blood
  • Disseminated Intravascular Coagulation / chemically induced
  • Disseminated Intravascular Coagulation / prevention & control*
  • Endotoxins / toxicity
  • Female
  • Fibrin / metabolism
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinogen / metabolism
  • Guanidines / administration & dosage
  • Guanidines / pharmacology*
  • Kidney Glomerulus / pathology
  • Partial Thromboplastin Time
  • Platelet Count
  • Prothrombin Time
  • Rats
  • Rats, Inbred Strains
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / pharmacology
  • Thrombosis / pathology

Substances

  • Endotoxins
  • Fibrin Fibrinogen Degradation Products
  • Guanidines
  • Serine Proteinase Inhibitors
  • ONO 3307
  • Fibrin
  • Fibrinogen