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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Bile Reflux
Ketamine
Lipopolysaccharides
Stomach
Hemorrhage
Duodenogastric Reflux
Ileus
Hemoglobins
Gastrointestinal Contents
Heme Oxygenase-1
Gastric Emptying
Nitric Oxide Synthase Type II
Carbon Monoxide
Prostaglandin-Endoperoxide Synthases
Dextrans
Bile Acids and Salts
Genes
Prostaglandins
Nitric Oxide
Anti-Inflammatory Agents

Keywords

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

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Ketamine suppresses LPS-induced bile reflux and gastric bleeding in the rat. / Ward, Jeremy L.; Adams, Sasha D.; Delano, Benjamin A.; Clarke, Caroline; Radhakrishnan, Ravi; Weisbrodt, Norman W.; Mercer, David W.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 68, No. 1, 01.2010, p. 69-75.

Research output: Contribution to journalArticle

Ward, Jeremy L. ; Adams, Sasha D. ; Delano, Benjamin A. ; Clarke, Caroline ; Radhakrishnan, Ravi ; Weisbrodt, Norman W. ; Mercer, David W. / Ketamine suppresses LPS-induced bile reflux and gastric bleeding in the rat. In: Journal of Trauma - Injury, Infection and Critical Care. 2010 ; Vol. 68, No. 1. pp. 69-75.
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