{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:12:45Z","timestamp":1786450365204,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54NS112107"],"award-info":[{"award-number":["U54NS112107"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cyanide\u2014a fast-acting poison\u2014is easy to obtain given its widespread use in manufacturing industries. It is a high-threat chemical agent that poses a risk of occupational exposure in addition to being a terrorist agent. FDA-approved cyanide antidotes must be given intravenously, which is not practical in a mass casualty setting due to the time and skill required to obtain intravenous access. Glyoxylate is an endogenous metabolite that binds cyanide and reverses cyanide-induced redox imbalances independent of chelation. Efficacy and biochemical mechanistic studies in an FDA-approved preclinical animal model have not been reported. Therefore, in a swine model of cyanide poisoning, we evaluated the efficacy of intramuscular glyoxylate on clinical, metabolic, and biochemical endpoints. Animals were instrumented for continuous hemodynamic monitoring and infused with potassium cyanide. Following cyanide-induced apnea, saline control or glyoxylate was administered intramuscularly. Throughout the study, serial blood samples were collected for pharmacokinetic, metabolite, and biochemical studies, in addition, vital signs, hemodynamic parameters, and laboratory values were measured. Survival in glyoxylate-treated animals was 83% compared with 12% in saline-treated control animals (p\u2009&amp;lt;\u2009.01). Glyoxylate treatment improved physiological parameters including pulse oximetry, arterial oxygenation, respiration, and pH. In addition, levels of citric acid cycle metabolites returned to baseline levels by the end of the study. Moreover, glyoxylate exerted distinct effects on redox balance as compared with a cyanide-chelating countermeasure. In our preclinical swine model of lethal cyanide poisoning, intramuscular administration of the endogenous metabolite glyoxylate improved survival and clinical outcomes, and ameliorated the biochemical effects of cyanide.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac116","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T14:57:11Z","timestamp":1667487431000},"page":"90-105","source":"Crossref","is-referenced-by-count":5,"title":["Intramuscular administration of glyoxylate rescues swine from lethal cyanide poisoning and ameliorates the biochemical sequalae of cyanide intoxication"],"prefix":"10.1093","volume":"191","author":[{"given":"Vik S","family":"Bebarta","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of Colorado School of Medicine , Aurora, Colorado 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of 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Physical Pharmacy, Purdue University , West Lafayette, Indiana 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry R","family":"Boss","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Diego, California 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari","family":"Mahon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beckman Laser Institute, University of California , Irvine, California 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beckman Laser Institute, University of California , Irvine, California 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory T","family":"Knipp","sequence":"additional","affiliation":[{"name":"Department of Industrial and Physical Pharmacy, Purdue University , West Lafayette, Indiana 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent Jo","family":"Davisson","sequence":"additional","affiliation":[{"name":"Department of Industrial and Physical Pharmacy, Purdue University , West Lafayette, Indiana 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall T","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah , Salt Lake City, Utah 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calum A","family":"MacRae","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital , Boston, Massachusetts 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Rutter","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Howard Hughes Medical Institute, University of Utah , Salt Lake City, Utah 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E","family":"Gerszten","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beth Israel Deaconess Medical Center , Boston, Massachusetts 02115, USA"},{"name":"Broad Institute , Cambridge, Massachusetts 02142, USA"},{"name":"Harvard Medical School , Boston, Massachusetts 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5032-7250","authenticated-orcid":false,"given":"Anjali K","family":"Nath","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beth Israel Deaconess Medical Center , Boston, Massachusetts 02115, USA"},{"name":"Broad Institute , Cambridge, Massachusetts 02142, USA"},{"name":"Harvard Medical School , Boston, Massachusetts 02115, 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