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

Autor: Piel S; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA. piels@chop.edu.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA. piels@chop.edu.; Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany. piels@chop.edu.; CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany. piels@chop.edu., McManus MJ; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Heye KN; Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, USA., Beaulieu F; Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, USA., Fazelinia H; Proteomics Core Facility, The Children's Hospital of Philadelphia, Philadelphia, USA., Janowska JI; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., MacTurk B; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Starr J; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Gaudio H; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Patel N; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Hefti MM; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA., Smalley ME; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA., Hook JN; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA., Kohli NV; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Bruton J; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Hallowell T; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Delso N; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Roberts A; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Lin Y; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Ehinger JK; Mitochondrial Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.; Otorhinolaryngology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.; Otorhinolaryngology, Head and Neck Surgery, Skåne University Hospital, Lund, Sweden., Karlsson M; Neurosurgery, Rigshospitalet, Copenhagen, Denmark., Berg RA; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Morgan RW; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA., Kilbaugh TJ; Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jun 15; Vol. 14 (1), pp. 13852. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1038/s41598-024-64317-9
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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