Journal article
Attenuation of mitochondrial dysfunction in a ventricular fibrillation swine model of cardiac arrest treated with carbon monoxide
Resuscitation, v 213, 110647
01 Aug 2025
PMID: 40383501
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality. Despite aggressive supportive care and use of targeted temperature management, half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. Development of neuroprotective therapeutics is critical to improving outcomes. One promising readily available agent that has shown benefit is carbon monoxide (CO).
We utilize a swine model of ventricular fibrillation (VF) arrest to assess the therapeutic effect of CO on cellular measures. All animals underwent VF arrest followed by cardiopulmonary resuscitation until achievement of return of spontaneous circulation (ROSC) or the 20 min mark. One hour following ROSC, animals were randomized to the Cardiac Arrest group (VF alone) versus the CO group (VF treated with CO). Animals in the CO group were administered low dose CO of 200 ppm for two hours. At three hours post-ROSC period, all animals were euthanized for tissue and blood collection for mitochondrial respiration (cortical and hippocampal tissue) and the downstream biomolecular analysis.
The primary findings were an overall improvement in mitochondrial respiration and ATP concentrations in the brain from animals in the CO group. In addition, we also report the use of cell-free DNA as a biomarker to localize the site of tissue injury and our non-invasive optical monitoring device to assess cerebral metabolism.
CO may be a potential therapeutic to attenuate cellular injury in post-arrest.
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Details
- Title
- Attenuation of mitochondrial dysfunction in a ventricular fibrillation swine model of cardiac arrest treated with carbon monoxide
- Creators
- Tiffany S Ko - Children's Hospital of PhiladelphiaJohn C Greenwood - University of PennsylvaniaRyan W Morgan - Children's Hospital of PhiladelphiaBenjamin S Abella - University of PennsylvaniaFrances S Shofer - University of PennsylvaniaMcKenna Mason - Children's Hospital of PhiladelphiaDevora Weintraub - Children's Hospital of PhiladelphiaDevesh Bungatavula - Drexel UniversityAlistair Lewis - Children's Hospital of PhiladelphiaNicolina R Ranieri - Children's Hospital of PhiladelphiaArjun G Yodh - University of PennsylvaniaWesley B Baker - Children's Hospital of PhiladelphiaRodrigo M Forti - Children's Hospital of PhiladelphiaShih-Han Kao - Children's Hospital of PhiladelphiaSamuel S Shin - University of PennsylvaniaTodd J Kilbaugh - Children's Hospital of PhiladelphiaDavid H Jang (Corresponding Author) - Children's Hospital of Philadelphia
- Publication Details
- Resuscitation, v 213, 110647
- Publisher
- Elsevier
- Grant note
- P30 ES013508 / NIEHS NIH HHS R01 HL141386 / NHLBI NIH HHS P41 EB029460 / NIBIB NIH HHS R01 HL166592 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering and Science
- Web of Science ID
- WOS:001503852600002
- Scopus ID
- 2-s2.0-105007002390
- Other Identifier
- 991022197301704721
UN Sustainable Development Goals (SDGs)
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Critical Care Medicine
- Emergency Medicine