Endotoxin-induced lung injury in unanesthetized sheep: effect of methylprednisolone.

Our purpose was to study the effect of methylprednisolone (MPS) on endotoxin-induced lung injury. We used lung lymph flow and lymph protein content at sensitive indicators of pulmonary microvascular integrity in unanesthetized sheep. Seven animals were given E coli endotoxin (2 micrograms/kg) alone and also endotoxin with MPS pretreatment (30 mg/kg) in paired separate studies. The endotoxin injury was divided into an early hypertensive phase (30-90 minutes) characterized by a significant increase in pulmonary artery pressure (Ppa) and lymph flow, QL. This was followed later (3-5 hours) by a significant increase in protein-rich QL with normal pressures. MPS pretreatment significantly increased both injury phases in all animals. White cell count decreased in both groups; however, lymph beta-glucuronidase increased only in the nontreated group. Platelet count decreased in the nontreated group. Seven animals were then compared using endotoxin alone or with MPS treatment one hour after endotoxin. Only four of seven animals had a decrease in the lung injury after MPS treatment. We conclude that methylprednisolone is very effective in preventing lung injury, but only minimally effective in reversing the injury from endotoxin.