OKLAHOMA UNIV HEALTH SCIENCES CENTER OKLAHOMA CITY
We have succeeded in developing the first effective therapy to prevent death from septic shock induced by a 100 lethal dose of live E. coli organisms administered intravenously to dogs and nonhuman primates. The therapy consists of intermittent infusions of the corticosteroid, methylprednisolone sodium succinate, and the aminoglycoside antibiotic, gentamicin sulfate. Application of the therapy soon after initiation of E. coli administration has increased survival 7 days from 0 to 100 in both dogs and baboons. The purpose of this study was to delineate the exact mechanisms of protection of our corticosteroidantibiotic therapy, including how it is involved with the cardiovascular, metabolic, endocrinologic and host-defense systems of the septic animal. We have particularly emphasized evaluation of therapy interaction with adrenal cortex, lung, liver, and leukocytes. We have evaluated the roles of granulocytes in tissue injury in live organism-induced shock and assayed the role of corticosteroid in prevention of such injury. We have also assessed the significance of B-endorphin the pathogenesis of shock and effectiveness of therapy.