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To investigate Cl<jats:sub>2<\/jats:sub> concentration and gender-dependent ARDS severity. Sheep (n\u2009=\u200954) were exposed to air or Cl<jats:sub>2<\/jats:sub> premixed in air at a concentration of 50, 100, 200, and 300\u00a0ppm for 30\u00a0min under anesthesia\/analgesia and monitored for an additional 48\u00a0h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300\u00a0ppm group), and the pulmonary arterial pressure was lower (200\u00a0ppm group). The onset of mild ARDS (200\u2009&lt;\u2009PaO<jats:sub>2<\/jats:sub>\/FiO<jats:sub>2<\/jats:sub>\u2009\u2264\u2009300) was observed at 36\u00a0h post exposure in the 50\u00a0ppm group, whereas the 100\u00a0ppm group developed mild and moderate (100\u2009\u2264\u2009PaO<jats:sub>2<\/jats:sub>\/FiO<jats:sub>2<\/jats:sub>\u2009\u2264\u2009200) ARDS by 12 and 36\u00a0h after injury, respectively. The 200\u00a0ppm and 300\u00a0ppm groups developed moderate ARDS within 6 and 3\u00a0h after injury, respectively. The 300\u00a0ppm group progressed to severe (PaO<jats:sub>2<\/jats:sub>\/FiO<jats:sub>2<\/jats:sub>\u2009\u2264\u2009100) ARDS at 18\u00a0h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200\u00a0ppm and 300\u00a0ppm Cl<jats:sub>2<\/jats:sub> significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl<jats:sub>2<\/jats:sub> concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl<jats:sub>2<\/jats:sub> concentrations. No significant sex-dependent differences were found in measured endpoint variables.<\/jats:p>","DOI":"10.1038\/s41598-023-48720-2","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T21:21:59Z","timestamp":1702675319000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dose and gender dependence of chlorine inhalation in a conscious ovine model"],"prefix":"10.1038","volume":"13","author":[{"given":"Tuvshintugs","family":"Baljinnyam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Niimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Salsbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey M.","family":"Ouellette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clark R.","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Hirasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald A.","family":"Prough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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