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Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest

Piel, Sarah LU orcid ; McManus, Meagan J. ; Heye, Kristina N. ; Beaulieu, Forrest ; Fazelinia, Hossein ; Janowska, Joanna I. ; MacTurk, Bryce ; Starr, Jonathan ; Gaudio, Hunter and Patel, Nisha , et al. (2024) In Scientific Reports 14(1).
Abstract

Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days,... (More)

Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF’s protective mechanisms and optimize its therapeutic application in post-arrest care.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Asphyxia, Brain, Cardiac arrest, Dimethyl fumarate, Heart, Metabolism, Mitochondria, Post-arrest care
in
Scientific Reports
volume
14
issue
1
article number
13852
publisher
Nature Publishing Group
external identifiers
  • scopus:85196014645
  • pmid:38879681
ISSN
2045-2322
DOI
10.1038/s41598-024-64317-9
language
English
LU publication?
yes
id
0c5701b8-5716-4144-acb7-074c3425e78c
date added to LUP
2024-07-03 14:51:18
date last changed
2024-07-17 18:06:21
@article{0c5701b8-5716-4144-acb7-074c3425e78c,
  abstract     = {{<p>Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p &lt; 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF’s protective mechanisms and optimize its therapeutic application in post-arrest care.</p>}},
  author       = {{Piel, Sarah and McManus, Meagan J. and Heye, Kristina N. and Beaulieu, Forrest and Fazelinia, Hossein and Janowska, Joanna I. and MacTurk, Bryce and Starr, Jonathan and Gaudio, Hunter and Patel, Nisha and Hefti, Marco M. and Smalley, Martin E. and Hook, Jordan N. and Kohli, Neha V. and Bruton, James and Hallowell, Thomas and Delso, Nile and Roberts, Anna and Lin, Yuxi and Ehinger, Johannes K. and Karlsson, Michael and Berg, Robert A. and Morgan, Ryan W. and Kilbaugh, Todd J.}},
  issn         = {{2045-2322}},
  keywords     = {{Asphyxia; Brain; Cardiac arrest; Dimethyl fumarate; Heart; Metabolism; Mitochondria; Post-arrest care}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-64317-9}},
  doi          = {{10.1038/s41598-024-64317-9}},
  volume       = {{14}},
  year         = {{2024}},
}