Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia.
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."
Lobo
Suzana M
SM
Department of Intensive Care, Faculdade de Medicine de Sao José do Rio Preto, Brazil.
De Backer
Daniel
D
Sun
Qinghua
Q
Tu
Zizhi
Z
Dimopoulos
George
G
Preiser
Jean-Charles
JC
Nagy
Nathalie
N
Vray
Bernard
B
Vercruy
Vincent
V
Terzi
Renato Giuseppe Giovanni
RG
Vincent
Jean-Louis
JL
Tu
Zizi
Z
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
D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D002245:Carbon Dioxide; D009569:Nitric Oxide; D019344:Lactic Acid