Laparotomy attenuates lipopolysaccharide-induced gastric bleeding in the rat.

Lipopolysaccharide (LPS) increases systemic inflammation and causes duodenogastric reflux of bile and gastric bleeding. Laparotomy prevents gastric injury from the luminal irritant bile, but its effects on LPS-induced gastric injury are unknown. We hypothesized that laparotomy would diminish inflammation and attenuate gastric bleeding caused by LPS. In the rat, laparotomy, done either before or after administration of LPS, attenuated LPS-induced bile reflux, gastric bleeding, and cyclooxygenase-2, but not inducible nitric oxide synthase, expression when compared to controls given LPS. Laparotomy also blunted LPS-induced changes in serum cytokine production. These data suggest that laparotomy has gastroprotective effects by preventing LPS-induced bile reflux and gastric bleeding and by a mechanism mediated, at least in part by cyclooxygenase-2.

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

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.

Fasting exacerbates and feeding diminishes LPS-induced liver injury in the rat.

INTRODUCTION: Enteral nutrition improves clinical outcomes. The effects of feeding on LPS induced liver injury are unknown. We hypothesized that feeding would attenuate liver injury from LPS. METHODS: Fasted or fed rats were given LPS (20 mg/kg i.p.) or saline for 5 h and sacrificed. Serum aminotransferases and cytokines (immunoassay) were measured. Oxidative stress protein (iNOS, COX2, and HO1) assessments (Western immunoblot) were also obtained. RESULTS: In fasted rats, LPS significantly increased serum aminotransferase levels, enhanced hepatic COX2, iNOS, and HO1 immunoreactivity, and increased serum cytokine levels when compared to controls. While feeding diminished liver enzymes, attenuated expression of COX2 and iNOS, and blunted production of pro-inflammatory cytokines, it did not modulate LPS-induced expression of the anti-inflammatory markers HO1 and IL-10. CONCLUSION: These data suggest that feeding decreases liver injury by attenuating expression of pro-inflammatory mediators while maintaining expression of anti-inflammatory mediators, both systemically and locally.