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

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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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Acknowledgements

This project was funded by an operating grant from the Canadian Institutes of Health Research (MOP-CSB-53009) and a grant-in-aid from the George and Dorothy Davey Endowment for Brain Injury Research. P.Y.C. is an investigator with the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research. L.L.J. is a recipient of a Canada Graduate Scholarship from the Natural Science and Engineering Research Council of Canada and a doctoral research award from the Alberta Heritage Foundation of Medical Research. There is no financial conflict of interest in this work.

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Authors and Affiliations

  1. Department of Pediatrics, University of Alberta, Edmonton, Canada

    Tze-Fun Lee & Po-Yin Cheung

  2. Department of Psychiatry, University of Alberta, Edmonton, Canada

    Lauren L. Jantzie & Kathryn G. Todd

  3. NICU Royal Alexandra Hospital, 10240 Kingsway Avenue, T5H 3V9, Edmonton, Canada

    Po-Yin Cheung

Authors
  1. Tze-Fun Lee
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  2. Lauren L. Jantzie
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  3. Kathryn G. Todd
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  4. Po-Yin Cheung
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Corresponding author

Correspondence to Po-Yin Cheung.

Additional information

We are very grateful to Corinne Cote for her excellent assistance and technical expertise.

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Lee, TF., Jantzie, L.L., Todd, K.G. et al. Postresuscitation N-acetylcysteine treatment reduces cerebral hydrogen peroxide in the hypoxic piglet brain. Intensive Care Med 34, 190–197 (2008). https://doi.org/10.1007/s00134-007-0880-z

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  • DOI: https://doi.org/10.1007/s00134-007-0880-z

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