Beverly K. Beller

Increased survival with methylprednisolone treatment in canine endotoxin shock

Abstract The use of corticosteroids has been intensively studied for the treatment of endotoxin shock; however, there still remains much controversy over their use. This study was designed to determine the therapeutic value of treatment with methylprednisolone sodium succinate in the awake and anesthetized canine receiving LD 100 of Escherichia coli endotoxin by either intravenous slow infusion or bolus injection. Methylprednisolone (30 mg/kg) was administered initially at 15 min following the onset of endotoxin infusion and then at 90 min given a maintenance infusion of 15 mg/kg for 120 min. It was found that treatment with methylprednisolone significantly increased survival rate (83%) in dogs receiving LD 100 E. coli endotoxin by slow infusion in either the awake or anesthetized state. Both the 5-hr infusion and bolus injection of endotoxin produced a 100% mortality if steroid was not administered. Treatment with methylprednisolone did not alter the 100% mortality in the canine bolus-injected endotoxin shock model. Survival was associated with a normoglycemia and stabilized hematocrit, while death was accompanied by hypoglycemia and severe hemoconcentration.

Hypoglycemic response of blood to live Escherichia coli organisms and endotoxin

Abstract Progressively developing lethal hypoglycemia in dogs and baboons subjected to endotoxin or live E. coli shock has recently been reported by this laboratory. The purpose of the present study was to explore the possibility that accelerated glycolysis in blood might contribute to the hypoglycemia of shock. Experiments were carried out on canine heparinized blood drawn from nonfasted unanesthetized animals and maintained in vitro under controlled temperature conditions. Plasma glucose was determined with a Beckman glucose analyzer. LD100 to LD0 doses of E. coli endotoxin or live E. coli organisms, as estimated from parallel in vivo studies, were incubated with blood during a 6- to 7-hr period. Glucose blood concentrations, cumulative glucose utilization, and dose-response studies with endotoxin and live organisms were carried out. Paired control blood samples received equal volumes of saline in place of endotoxin or organisms. All studies were conducted on the blood from a colony of seven adult mongrel donor animals. Results demonstrated consistent accelerated glucose disappearance at all doses of endotoxin and organisms, in comparison to the controls with saline only added. LD100 experiments resulted in significantly greater disappearance rates of glucose as compared to LD0 studies, during the first 2 hr. Minimal threshold responses for accelerated glucose utilization were observed at levels above 104 organisms/ml of blood, while those for endotoxin were less than 10−6 mg/ml, both concentrations being sublethal when applied to the whole animal. At glucose concentrations less than 20 mg%, control and experimental curves tended to converge with the achievement of minimal values of about 10 mg%. Positive correlations were seen between rates of glucose disappearance, pH, and pCO2, suggesting accelerated metabolic activities by certain formed elements of the blood during the process of phagocytosis. Findings in in vitro studies were compared to those in eviscerated, nephrectomized dogs in which all sources for new glucose were eliminated, and similar accelerated rates of cumulative glucose utilization were observed between the animal and test tube experiments. Findings suggest that the excessive demand for glucose by certain blood components may explain in part the development of lethal hypoglycemia and acidemia in animals subjected to endotoxin- or live bacterial organism-induced shock.

Associated leukocyte responses in the lethal aspects of E. coli shock.

Dogs administered lethal injections of E. coli endotoxin or E. coli organisms develop systemic hypotension, hypoglycemia, and hepatosplanchnic dysfunction (1-4). Progressively decreasing blood glucose levels after endotoxin or E. coli administration are due in large part to depressed hepatic function, particularly gluconeogenesis (4-7). Accelerated glucose uptake has been reported following in vitro incubation of either endotoxin or live E. coli organisms in blood, and white blood cell (WBC) phagocytic activity has been implicated as the primary responsible factor (2). Increased phagocytic activity of the blood after endotoxin (8) has been traced to the buffy coat (9) and the leukocyte (10). Recent reports have shown circulating neutrophils to be of major importance in the clearance of bacterial organisms (11) or endotoxin (12) from the blood, while others have described beneficial effects of transfused WBCs in patients and animals in septic shock (13, 14). The purpose of the present study was to explore the responses of canine blood to the separate effects of E. coli organisms and E. coli endotoxin, particularly emphasizing the role of the WBC in the uptake of glucose in vitro and its possible relationship to survival in vivo. Materials and methods. In vivo experiments were carried out on 12 awake adult mongrel dogs during a 4-day period. On the fourth day, venous blood was drawn from each animal and additionally studied in the in vitro state. Animals, selected for robust health and absence of heart worms, were treated for intestinal parasites and conditioned in the animal facility for 3-6 weeks prior to use. Dogs with initial WBC counts between 7000 and 20,000/mm3 and hema-tocrits exceeding 37% were utilized in the experiments. In vivo studies. Unanesthetized, gently restrained animals were divided into paired control and experimental groups which were studied simultaneously.