Inhibition of the Generalized Shwartzman Reaction

The effect of hypofibrinogenemia on production of the generalized Shwartzman reaction (GSR) by the administration of Thorotrast (3 mI/kg) and Escherichia coil endotoxin (50 jzg) to rabbits was determined. Severe hypofibrinogenemia (fibrinogen less than 15 mg/ 100 ml) was produced by Arvin, a proteolytic coagulant from the venom of the Malayan pit viper, Agkistrodon rhodostoma. Development of the GSA was inhibited significantly only when hypofibrinogenemia was produced 30 hr before the preparatory injection of Thorotrast and maintained for the duration of the experiment. Severe hypofibrinogenemia of 2-20-hr duration before administration of endotoxin did not block the production of the GSR. Elevated levels of fibrinogen degradation products were demonstrated in the serum of all animals that received Arvin. The concentration of fibrinogen degradation products decreased markedly prior to death only in those animals that developed the GSR. The GSA was not observed in rabbits that received only Thorotrast and Arvin, although these animals had the highest levels of fibrinogen degradation products. The data suggest an essential role for fibrinogen or fibrinogen degradation products and endotoxin In the production of the GSR. T HE GENERALIZED SHWARTZMAN REACTION (GSR) has been produced classically in rabbits by two appropriately spaced intravenous injections of endotoxin. More recently, Thorotrast has been substituted for the first injection of endotoxin.2 Previous studies have demonstrated that production of the GSR can be blocked by granulocytopenia,3’4 thrombocytopenia,5’#{176} or anticoagulation.7’8 It is generally accepted that the GSR is the result of intravascular coagulation7 ” with deposition of fibrin in renal glomerular capillaries.9”2 To test further the postulate that the final common pathway in the production of the GSR is intravascular coagulation, experiments were carried out to determine whether the GSR could be blocked by severe hypofibrinogenemia. Arvin, a proteolytic, coagulant enzyme obtained from the crude venom of the Malayan pit viper, Agkistrodon rhodostoma, was used to produce hypo-