Ketamine suppresses LPS-induced bile reflux and gastric bleeding in the rat

Jeremy L. Ward, Sasha D. Adams, Benjamin A. Delano, Caroline Clarke, Ravi S. Radhakrishnan, Norman W. Weisbrodt, David W. Mercer

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: Although ketamine has many beneficial effects in a rat model of noninfectious inflammation with lipopolysaccharide (LPS), its effects on gut ileus are unknown. We hypothesized that ketamine would improve LPS-induced ileus and therefore examined its effects on gastric emptying and intestinal transit as well as duodenogastric bile reflux and associated gastric bleeding. Methods: Male rats received saline or ketamine (7 mg/kg ip) 1 hour before saline or LPS (20 mg/kg ip) for 5 hours. Thirty minutes before killing, rats received orogastric rhodamine B isothiocyanate-labeled dextran and 5 minutes later fluorescein isothiocyanate-labeled dextran via a duodenal catheter. GI contents were collected for dye, bile acid, and hemoglobin (index of bleeding) determinations. Results: LPS significantly impaired intestinal transit and increased duodenogastric bile reflux and gastric luminal hemoglobin content. Ketamine improved intestinal transit, prevented LPS-induced bile reflux, and diminished gastric bleeding. In mechanistic studies, ketamine also attenuated LPS-induced upregulation of the proinflammatory genes inducible nitric oxide synthase and cyclo-oxygenase-2 in the stomach but preserved expression of the anti-inflammatory gene heme-oxygenase-1 (Western blot). Conclusions: These data suggest that ketamine may prevent LPS-induced gastric bleeding by decreasing bile reflux through improved intestinal transit or by local changes in nitric oxide, prostaglandin, and carbon monoxide metabolism.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume68
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Bile reflux
  • GI transit
  • Gastric bleeding
  • Ketamine
  • Lipopolysaccharide

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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