oxyntomodulin and Escherichia-coli-Infections

We have determined the effect of lethal E. coli infusions in dogs on plasma concentrations of pancreatic and gastrointestinal-derived glucagon and have explored the contributions of each source of glucagon during the early and recovery phases of shock. We examined 18 adult dogs in three protocols: group I received LD100 E. coli alone, group II received LD100 E. coli + tobramycin (TOB), and group III received LD100 E. coli + TOB + methylprednisolone sodium succinate (MPSS). E. coli organisms were infused intravenously during a 1-hour period and each animal was monitored for 6 hours and observed for a 7-day recovery period. Plasma concentrations of pancreatic and gastrointestinal glucagon were determined by specific RIAs. The survival percentages (greater than 7 days) were 0% in group I, 17% in group II, and 83% in group III. Early progressive increases in plasma concentrations of pancreatic and gastrointestinal-derived glucagon, reaching statistical significance by 6 hours following the onset of E. coli administration, were seen in the three groups. The increase in gastrointestinal-derived glucagon was of a greater magnitude than that from the pancreas. Attenuation of the increase appeared to be achieved by corticosteroid infusion during its time of administration (6 hours). Recovery from shock was characterized by an exceptionally slow return (greater than or equal to 7 days) to control levels of glucagon in all recovering animals.

Topics: Animals; Blood Glucose; Blood Pressure; Dogs; Escherichia coli Infections; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Heart Rate; Methylprednisolone Hemisuccinate; Shock, Septic; Tobramycin

We postulate that high plasma concentrations of gastrointestinal-derived glucagon may be used to identify severe sepsis and correlate with the effect of therapy. Eighteen adult dogs were separated into three groups: Group I-LD100 E. coli alone, group II-LD100 E. coli + tobramycin (TOB) and group III-LD100 E. coli + TOB + methylprednisolone sodium succinate (MPSS). E. coli was infused intravenously for one hour. Each animal was monitored for six hours and observed for a 7-day recovery period. Percent survival (greater than 7 days): I = 0%, II = 17% and III = 83%. Concentrations of gastrointestinal glucagon were 3417 pg/ml in group I, 5167 pg/ml in group II and 1081 pg/ml in group III at six hours after E. coli infusion. In group III these concentration returned to control values by 7 days after E. coli infusion. Increases in gastrointestinal glucagon were more readily induced by E. coli infusion than those of pancreatic glucagon. Gastrointestinal glucagon concentrations were related to the severity of E. coli induced shock and the beneficial effects of MPSS/TOB therapy. Therefore, plasma gastrointestinal glucagon concentrations may be useful in recognizing the presence of severe sepsis and directly related to the beneficial effects of therapy.

Topics: Animals; Dogs; Drug Therapy, Combination; Escherichia coli Infections; Gastrointestinal Hormones; Glucagon-Like Peptides; Methylprednisolone Hemisuccinate; Prognosis; Sepsis; Tobramycin