• F Tamion, V Richard, G Bonmarchand, J Leroy, M Hiron, M Daveau, C Thuillez, and J P Lebreton.
• IFRMP 23, INSERM E9920, Rouen University Hospital, France.
• Crit. Care Med. 2000 Jul 1; 28 (7): 2522-7.

ObjectivesIntestinal ischemia/reperfusion during hemorrhage and resuscitation may be a major trigger for cytokine expression. To assess whether free radicals produced on tissue reperfusion may play a role in the inflammatory response after hemorrhage, we tested the effect of a free radical scavenger on the production of inflammatory cytokines in a rat model of hemorrhagic shock.DesignA prospective, controlled animal study.SettingA university research laboratory.SubjectsMale Wistar rats.InterventionsHemorrhage was induced in anesthetized rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed by NaCl 0.9% to maintain arterial blood pressure within control values. Treated rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG; 20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr).Measurements And Main ResultsMPG reduced the volume of saline necessary to restore blood pressure during resuscitation (untreated 85+/-6; MPG 35+/-5 mL/kg; p < .05). As compared with untreated rats, MPG markedly reduced the systemic and mesenteric plasma concentrations of tumor necrosis factor (TNF)-alpha (as measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at the end of resuscitation. MPG also reduced TNF-alpha and IL-6 mRNA expression (as measured by reverse transcriptase-polymerase chain reaction) assessed in peritoneal macrophages isolated from shock rats. Finally, in vitro experiments showed that MPG also markedly reduced the mRNA expression and release of TNF-alpha and IL-6 in peritoneal macrophages isolated from normal rats and subjected to hypoxia and reoxygenation.ConclusionReactive oxygen species contribute to the production of proinflammatory cytokines during posthemorrhage resuscitation. Free radicals scavengers may be a useful treatment in the prevention of the systemic inflammatory response that occurs in shock states.

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