title: Hypoxia of canine gastric mucosa caused by Escherichia coli sepsis and prevented with methylprednisolone therapy.
abstract: To test the hypothesis that sepsis causes in vivo changes in nutrient microcirculatory blood flow to gastric surface epithelium, cellular oxygenation (PO2), and transmembrane potential difference, measured by an ultramicroelectrode, were studied before, during, and after a 1-h intravenous infusion of live E. coli organisms. A "high-dose" infusion (1.0-1.4 x 10(10) organisms/kg) resulted in a hyperdynamic septic state; a "low-dose" infusion (0.3-0.7 x 10(10) organisms/kg) caused no significant systemic hemodynamic changes except a decline in mean arterial blood pressure. Both doses, however, caused a significant and persistent decline in epithelial PO2 and potential difference. The rate of fall was dose-related but was not related to total gastric blood flow, which remained normal with both high- and low-dose infusions. Treatment with methylprednisolone 30 min after the start of infusion ameliorated mucosal hypoxia and restored potential difference to normal; recovery was maintained for 2 h after the septic insult. Light microscopy of the gastric mucosa subjected to high-dose infusion showed focal and confluent interstitial edema with evaluation of surface epithelium away from dilated capillaries in the lamina propria near the apices of the faveoli. Methylprednisolone treatment completely prevented these changes. We conclude that hypoxia of gastric surface epithelium at a time when total gastric blood flow is normal reflects impairment of nutrient subepithelial microcirculatory blood flow. Decline in transmembrane potential difference before cellular PO2 reaches rate-limiting concentrations indicates that sepsis has a dual effect: direct inhibition of epithelial metabolism as well as redistribution of microcirculatory blood flow. Methylprednisolone provided dramatic protection to the canine gastric mucosa, enhancing microcirculatory blood flow to apical gastric epithelium, maintaining normal capillary permeability and protecting cellular function during and after sepsis.
mesh_terms: D000818:Animals; D004285:Dogs; D004927:Escherichia coli Infections / Q000503:physiopathology*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008775:Methylprednisolone / Q000031:analogs & derivatives*; D008776:Methylprednisolone Hemisuccinate / Q000627:therapeutic use*; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000032:analysis; D018805:Sepsis / Q000503:physiopathology*
chemical_list: D008776:Methylprednisolone Hemisuccinate; D010100:Oxygen; D008775:Methylprednisolone