USE OF PROSTAGLANDIN I-2 ANALOG IN TREATMENT OF MASSIVE HEPATIC-NECROSIS ASSOCIATED WITH ENDOTHELIAL-CELL INJURY AND DIFFUSE SINUSOIDAL FIBRIN DEPOSITION

Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of p rostaglandin I-2, beraprost sodium, was administered to rats given eit her dimethylnitrosamine, carbon tetrachloride, or endotoxin following Corynebacterium parvum administration the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosami ne and endotoxin/Corynebacterium parvum models, where fibrin depositio n in the hepatic sinusoids occurs, as compared to the carbon tetrachlo ride model, where such fibrin deposition does not occur. Beraprost sod ium reduced the expected increase of portal venous pressure in the end otoxin/Corynebacterium parvum model without affecting plasma thrombin- antithrombin III complex levels. Beraprost sodium also significantly r educed cell killing of both isolated rat hepatocytes and hepatic sinus oidal endothelial cells exposed to tert-butyl hydroperoxide; when comp ared to controls. Beraprost sodium could prove to be a therapeutic can didate for the treatment of hepatic necrosis, particularly in cases as sociated with fibrin deposition in the hepatic sinusoids because of it s fibrin clot-clearing action.