Metabolic and cardiovascular effects of endotoxin infusion in conscious unrestrained rats: effects of methylprednisolone and BW755C.

Infusion of Escherichia coli endotoxin (41.7 micrograms kg-1 min-1 i.v. for 4 h; 10 mg kg-1 total) in conscious unrestrained rats produced an increase in heart rate and a gradual decrease in arterial blood pressure. Initially plasma glucose was transiently elevated but fell to hypoglycaemic values in the 1-2 h before death. There was a marked elevation in the plasma concentrations of lactate, thromboxane B2, and 6-keto prostaglandin F1 alpha, (PGF1 alpha). Methylprednisolone treatment (two doses of 30 mg kg-1) significantly reduced mortality, provided the first dose was given before commencing the endotoxin infusion; there was no effect on mortality if it was given 2 h after starting the endotoxin infusion. Methylprednisolone pretreatment maintained arterial blood pressure and plasma glucose and prevented the increase in plasma lactate in rats given endotoxin. Methylprednisolone treatment did not modify the increase in plasma thromboxane B2 but attenuated the increase in plasma 6-keto PGF1 alpha concentrations. Pretreatment with BW755C, an inhibitor of both cyclooxygenase and lipoxygenase enzymes, completely prevented the increase in plasma prostanoid concentrations but did not improve survival or significantly modify any other detrimental effects of endotoxin. It is suggested that the beneficial effects of methylprednisolone in this model of endotoxin shock are not related to a reduction in the formation of pharmacologically active arachidonic acid metabolites.