The influence of large doses of hydrocortisone on the generalized Shwartzman reaction in rabbit

Abstract

The influence of large doses (50 mg/kg) of hydrocortisone, given after both or only after second endotoxin dose, on the generalized Shwartzman reaction was studied. The effect of hydrocortisone alone was also investigated. The hydrocortisone injection after the first endotoxin dose lessened the decrease in platelet count but this effect was not observed after the second endotoxin dose. The addition of hydrocortisone to endotoxin did not change the pattern of fibrinogen concentration in plasma but did increase the frequency of positive ethanol gelation test. The Fibrinogen/Fibrin Related Antigen content in serum rose gradually throughout the experiments, especially in animals given hydrocortisone after both endotoxin doses. The injections of hydrocortisone alone inhibited fibrinolytic activity in euglobulins but did not change the content of plasminogen activator in the outer medullary zone of rabbit kidney. In comparison with results of previous studies on generalized Shwartzman reaction (Thrombos. Res.: 6 , 399, 1975), the addition of hydrocortisone to endotoxine increased the inhibition of fibrinolytic activity in euglobulins. The decrease of plasminogen activator content in the outer medullary zone of kidneys was less pronounced when first hydrocortisone injection followed the provocative endotoxin dose than after both injections of endotoxin and hydrocortisone. Injections of hydrocortisone following both doses of endotoxin increased fibrin deposition within kidney glomeruli. It is supposed that this effect is due to the inhibited release of tissue plasminogen activator in rabbit kidney after large doses of hydrocortisone.