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Intensive Care Medicine
Published in: Intensive Care Medicine 1/2008

01-01-2008 | Experimental

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

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

Published in: Intensive Care Medicine | Issue 1/2008

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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.
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Metadata
Title
Postresuscitation N-acetylcysteine treatment reduces cerebral hydrogen peroxide in the hypoxic piglet brain
Authors
Tze-Fun Lee
Lauren L. Jantzie
Kathryn G. Todd
Po-Yin Cheung
Publication date
01-01-2008
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 1/2008
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0880-z

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