Postresuscitation N-acetylcysteine treatment reduces cerebral hydrogen peroxide in the hypoxic piglet brain

Tze Fun Lee, Lauren L. Jantzie, Kathryn G. Todd, Po Yin Cheung

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Reactive 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. Design: Controlled, block-randomized animal study. Setting: University animal research laboratory. Subjects: Newborn piglets (1-3 days, 1.7-2.1 kg). Interventions: At 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 results: Newborn 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 2 h 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 100 mg/kg/h also increased the cerebral extracellular taurine levels. Conclusion: In newborn piglets with hypoxia-reoxygenation, postresuscitation administration of N-acetylcysteine reduces cerebral HPO production and oxidative stress, probably through a taurine-related mechanism.

Original languageEnglish (US)
Pages (from-to)190-197
Number of pages8
JournalIntensive Care Medicine
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Keywords

  • Hydrogen peroxide
  • Hypoxia-reoxygenation
  • N-acetylcysteine
  • Neonates
  • Oxidative stress

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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