• Tze-Fun Lee, Lauren L Jantzie, Kathryn G Todd, and Po-Yin Cheung.
• Department of Pediatrics, University of Alberta, Edmonton, Canada.
• Intensive Care Med. 2008 Jan 1; 34 (1): 190-7.

ObjectiveReactive oxygen species have been implicated in the pathogenesis of hypoxia-reoxygenation injury. However, little information is known regarding the temporal profile of cerebral hydrogen peroxide (HPO) production and its response to N-acetylcysteine (an antioxidant) administration during neonatal hypoxia-reoxygenation. Using an acute swine model of neonatal hypoxia-reoxygenation, we examined the short-term neuroprotective effects of N-acetylcysteine on cerebral HPO production and oxidative stress in the brain.DesignControlled, block-randomized animal study.SettingUniversity animal research laboratory.SubjectsNewborn piglets (1-3 days, 1.7-2.1 kg).InterventionsAt 5 min after reoxygenation, piglets were given either saline or N-acetylcysteine (20 or 100 mg/kg/h) in a blinded, randomized fashion.Measurements And ResultsNewborn piglets were block-randomized into a sham-operated group (without hypoxia-reoxygenation, n = 5) and three hypoxic-reoxygenated groups (2 h of normocapnic alveolar hypoxia followed by 2h of reoxygenation, n = 7/group). Heart rate, mean arterial pressure, cortical HPO concentration, amino acid levels in cerebral microdialysate, and cerebral tissue glutathione and lipid hydroperoxide levels were examined. Hypoxic piglets were hypotensive and acidotic, and they recovered similarly in all hypoxic-reoxygenated groups. In hypoxic-reoxygenated control piglets, the cortical HPO concentration gradually increased during reoxygenation. Both doses of N-acetylcysteine abolished the increased HPO concentration and oxidized glutathione levels and tended to reduce the glutathione ratio and lipid hydroperoxide levels in the cerebral cortex (p = 0.08 and p = 0.1 vs. controls, respectively). N-acetylcysteine at 100mg/kg/h also increased the cerebral extracellular taurine levels.ConclusionIn newborn piglets with hypoxia-reoxygenation, postresuscitation administration of N-acetylcysteine reduces cerebral HPO production and oxidative stress, probably through a taurine-related mechanism.

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