title: Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia.
abstract: Whether the gut alterations seen during sepsis are caused by microcirculatory hypoxia or disturbances in cellular metabolic pathways associated with mitochondrial respiration remains controversial. We hypothesized that hypoperfusion or hypoxia and local production of nitric oxide might play an important role in the development of gut mucosal injury during endotoxic shock and investigated their roles by using differing levels of fluid resuscitation and occlusion of the superior mesenteric artery (SMA). Anesthetized New Zealand rabbits were allocated to group I (sham, n = 8); group II [low-dose endotoxin (LPS, Escherichia coli-055:B5, 150 microg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group III [high-dose LPS (1 mg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group IV [high-dose LPS (1 mg/kg)/hypovolemia (4 ml x kg-1 x h(-1) fluids); n = 8]; and group V [SMA ligation/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 4]. Luminal gut lactate concentrations and PCO2 gap increased in groups IV and V (P < 0.05), reflecting alterations in gut perfusion. Interestingly, significant histological alterations were observed in all LPS groups but not in group V. Blood and luminal gut nitrate/nitrite concentrations increased only in group IV. The mechanism of gut injury in endotoxic shock seems unrelated to hypoxia and release of nitric oxide. Gut dysfunction may occur as a result of so-called "cytopathic hypoxia."
authors.affiliation: Department of Intensive Care, Faculdade de Medicine de Sao José do Rio Preto, Brazil.
authors.forename: Suzana M
authors.initials: SM
authors.lastname: Lobo
authors.forename: Daniel
authors.initials: D
authors.lastname: De Backer
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.forename: Zizhi
authors.initials: Z
authors.lastname: Tu
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Preiser
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nagy
authors.forename: Bernard
authors.initials: B
authors.lastname: Vray
authors.forename: Vincent
authors.initials: V
authors.lastname: Vercruy
authors.forename: Renato Giuseppe Giovanni
authors.initials: RG
authors.lastname: Terzi
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Zizi
authors.initials: Z
authors.lastname: Tu
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D007082:Ileum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D011817:Rabbits; D012039:Regional Blood Flow; D018805:Sepsis / Q000378:metabolism / Q000473:pathology; D012772:Shock, Septic / Q000378:metabolism / Q000473:pathology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D002245:Carbon Dioxide; D009569:Nitric Oxide; D019344:Lactic Acid