Journal article
Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest
Scientific reports, Vol.14(1), 13852
06/15/2024
DOI: 10.1038/s41598-024-64317-9
PMCID: PMC11180202
PMID: 38879681
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, 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.
Details
- Title: Subtitle
- Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest
- Creators
- Sarah Piel - Children's Hospital of PhiladelphiaMeagan J McManus - Children's Hospital of PhiladelphiaKristina N Heye - Children's Hospital of Philadelphiarest Beaulieu - Children's Hospital of PhiladelphiaHossein Fazelinia - Children's Hospital of PhiladelphiaJoanna I Janowska - Children's Hospital of PhiladelphiaBryce MacTurk - Children's Hospital of PhiladelphiaJonathan Starr - Children's Hospital of PhiladelphiaHunter Gaudio - Children's Hospital of PhiladelphiaNisha Patel - Children's Hospital of PhiladelphiaMarco M Hefti - University of IowaMartin E Smalley - University of IowaJordan N Hook - University of IowaNeha V Kohli - Children's Hospital of PhiladelphiaJames Bruton - Children's Hospital of PhiladelphiaThomas Hallowell - Children's Hospital of PhiladelphiaNile Delso - Children's Hospital of PhiladelphiaAnna Roberts - Children's Hospital of PhiladelphiaYuxi Lin - Children's Hospital of PhiladelphiaJohannes K Ehinger - Lund UniversityMichael Karlsson - RigshospitaletRobert A Berg - Children's Hospital of PhiladelphiaRyan W Morgan - Children's Hospital of PhiladelphiaTodd J Kilbaugh - Children's Hospital of Philadelphia
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.14(1), 13852
- Publisher
- Nature Publishing Group
- DOI
- 10.1038/s41598-024-64317-9
- PMID
- 38879681
- PMCID
- PMC11180202
- eISSN
- 2045-2322
- Language
- English
- Date published
- 06/15/2024
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984642858202771
Metrics
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