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."

Comparison of the effects of lactated Ringer solution with and without hydroxyethyl starch fluid resuscitation on gut edema during severe splanchnic ischemia

“…The lumen of the proximal catheter was used for continuous infusion and the lumen of the distal catheter was used to recover the gut luminal perfusate every hour. The details of this technique were described elsewhere (10,11). In a second gut segment, a tonometric catheter (TRIP ® Tonometry Catheter, Datex, Finland) was placed through a minimal antimesenteric wall incision and secured with a purse-string suture.…”

Pneumonia-Induced Sepsis and Gut Injury: Effects of a Poly-(ADP-Ribose) Polymerase Inhibitor

“…The lumen of the proximal catheter was used for continuous infusion and the lumen of the distal catheter was used to recover the gut luminal perfusate (GLP) every hour. This technique has been described in detail elsewhere [18]. In a second gut segment, a tonometric catheter (TRIP Tonometry Catheter, Datex, Finland) was placed through a minimal antimesenteric wall incision and secured with a pursestring suture.…”

Efeitos hemodinâmicos sistêmicos e regionais da ressuscitação volêmica com solução salina hipertônica e isoncótica guiada pela saturação venosa mista de oxigênio em modelo experimental de choque séptico

“…Atribuímos a redução expressiva da utilização de oxigênio observada aos efeitos deletérios da hipoperfusão presente na sepse e ao efeito direto da endotoxina no metabolismo de oxigênio do trato gastrointestinal (Lobo et al, 2003).…”

“…Diferentemente do que ocorre em outras condições de choque, em que existe diminuição da oferta de oxigênio por diminuição da pressão parcial de oxigênio arterial (hipóxia hipóxica) ou redução na concentração de hemoglobina (hipóxia anêmica), na sepse observamos uma lesão celular que persiste mesmo após a normalização da oferta de oxigênio e até mesmo dos fluxos regionais (hipóxia citopática) além da redução do fluxo sanguíneo (hipóxia isquêmica), (Lobo et al, 2003).…”