Effects of methylprednisolone upon vascular permeability changes in endotoxic shock

This study was designed to examine glucocorticoid effects on increases in vascular permeability caused by endotoxic shock in dogs anesthetized with pentobarbital sodium (30 mg/kg). Methylprednisolone sodium succinate was administered IV in two doses (30 mg/kg each) before Escherichia coli endotoxin was administered (0.5 mg/kg). Samples of serum and lymph from the left thoracic duct were collected for measurement of total protein and separation by polyacrylamide gel electrophoresis. The same four protein electrophoretic fractions with molecular weights (M.W.) ranging from 60,000 to 1,000,000 were consistently chosen for analysis. Methylprednisolone treatment given prior to endotoxin administration resulted in an attenuation of the early increase in total protein flux and lymph to plasma protein (L/P) ratio and prevented significant increases in the permeability surface area product observed in the group given endotoxin alone. Endotoxin administration alone resulted in significant increases in the permeability-surface area product and L/P ratio for all four electrophoretic fractions. Pretreatment with glucocorticoid partially attenuated the increase in the L/P ratio for only those fractions of 100,000 M.W. or less. These results suggest MP provides partial but not complete protection from increases in vascular permeability during endotoxic shock.