{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:22:05Z","timestamp":1787613725581,"version":"build-2736575974"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["R01HL166592"],"award-info":[{"award-number":["R01HL166592"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","award":["R01ES037322"],"award-info":[{"award-number":["R01ES037322"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["R01NS113945"],"award-info":[{"award-number":["R01NS113945"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Carbon monoxide (CO) poisoning remains a major cause of toxicologic morbidity and mortality and is a leading cause of acute neurologic injury among poisoned patients, yet the mechanisms underlying cerebral bioenergetic dysfunction remain incompletely understood. In addition to impaired oxygen delivery through carboxyhemoglobin (COHb) formation, CO poisoning is associated with mitochondrial respiratory dysfunction and cerebral metabolic injury. We characterized systemic physiology, cerebral metabolism, mitochondrial bioenergetics, and exploratory translational biomarkers in a swine model of acute CO poisoning. Yorkshire swine underwent sham exposure or inhalational CO exposure at 1,000 or 2,000\u2009ppm with serial physiologic monitoring, arterial blood gas analysis, cerebral microdialysis, high-resolution mitochondrial respirometry, ATP quantification, western blotting, and histologic\/immunohistochemical analyses. Peripheral blood mononuclear cell (PBMC) mitochondrial respiration was explored as a systemic correlate of cerebral mitochondrial function. CO exposure produced dose-dependent elevations in COHb and lactate with associated metabolic acidosis and hemodynamic impairment. Cerebral microdialysis demonstrated variable lactate-to-pyruvate ratios, whereas extracellular glycerol was significantly elevated during late exposure\/recovery following severe CO exposure, consistent with membrane injury and metabolic dysfunction. Mitochondrial respiration was impaired in both cortical and hippocampal tissue, with Complex IV-linked respiration among the most consistently affected respiratory states. Cortical ATP content was significantly reduced in severely exposed animals, supporting cerebral bioenergetic failure. Western blot analysis demonstrated increased HO-1 expression without significant reductions in citrate synthase or Complex IV protein abundance, suggesting functional respiratory inhibition rather than loss of mitochondrial content. Collectively, these findings demonstrate that acute CO poisoning produces early cerebral bioenergetic dysfunction characterized by impaired mitochondrial respiration, ATP depletion, and metabolic alterations, while supporting the exploratory potential of PBMC mitochondrial respiration as a translational biomarker of cerebral mitochondrial dysfunction.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag093","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:18:34Z","timestamp":1785323914000},"source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial dysfunction, cerebral metabolic crisis, and exploratory bioenergetic biomarkers in a translational swine model of acute carbon monoxide poisoning"],"prefix":"10.1093","volume":"209","author":[{"given":"Abigail","family":"Insana","sequence":"first","affiliation":[{"name":"Drexel University , Philadelphia, PA 19104,","place":["United 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States"]},{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Baak","sequence":"additional","affiliation":[{"name":"Resuscitation Science Center, The Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]},{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Starr","sequence":"additional","affiliation":[{"name":"Resuscitation Science Center, The Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]},{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarelis","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Resuscitation Science Center, The Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]},{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes K","family":"Ehinger","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine, Department of Clinical Sciences Lund, Lund University , Lund SE-221 84,","place":["Sweden"]},{"name":"Otorhinolaryngology, Head and Neck Surgery, Department of Clinical Sciences Lund, Lund University , Lund SE-221 84,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd J","family":"Kilbaugh","sequence":"additional","affiliation":[{"name":"Resuscitation Science Center, The Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]},{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104,","place":["United States"]},{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela N","family":"Viaene","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]},{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley B","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104,","place":["United States"]},{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1213-6971","authenticated-orcid":false,"given":"David H","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104,","place":["United 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