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Due to reduced tolerance to resuscitation fluids and prolonged evacuation times, its management poses substantial challenges. Whether 4-phenylbutyric acid (PBA) can protect vital organ function and extend the golden period for UHS at high altitudes remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats airlifted from Chongqing to Lhasa were used to establish a UHS model. The experiment consisted of three parts: Part 1 investigated PBA\u2019s effect on extending the golden period (prehospital treatment window). Specifically, using a high-altitude rat model of UHS, we observe the duration that PBA\u2009+\u2009LR maintains mean arterial pressure (MAP) at 50\u201360\u00a0mmHg without definitive hemostasis; Parts 2 and 3 involve hypotensive maintenance of MAP at 50\u201360\u00a0mmHg for 1 and 2\u00a0h, respectively, prior to definitive hemostasis, simulating 1-h and 2-h prehospital phases. After hypotensive maintenance, definitive hemostasis is performed. Parameters including vital organ injury markers, blood gas profiles, and survival rates were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In Part 1, PBA (20\u00a0mg\/kg) reduced blood loss by 13.3% (from 53.6\u2009\u00b1\u20092.4% to 45.28\u2009\u00b1\u20093.4%) and resuscitation fluid volume by 28% compared to LR alone. PBA (20\u00a0mg\/kg) prolonged the duration of sustained hypotensive resuscitation by 243% (from 39\u2009\u00b1\u20094.6\u00a0min to 134\u2009\u00b1\u200910.6\u00a0min) compared to LR, stabilized hemodynamics, and improved 2-h survival from 12.5% to 62.5%. In Part 2, 20\u00a0mg\/kg PBA attenuated vital organ damage, increased 72-h survival from 18.7% (LR group) to 50% (20\u00a0mg\/kg PBA group), and meanwhile reduced blood loss by 7.7% and resuscitation fluid volume by 16.3% compared to LR alone. In Part 3, despite extending hypotensive resuscitation to 2\u00a0h, PBA still significantly ameliorated organ function, reduced blood loss, decreased fluid administration, and enhanced 72-h survival in rats from 0% (LR group) to 31.25% (20\u00a0mg\/kg PBA group).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PBA administration during hypotensive resuscitation protects vital organs (heart, liver, kidney), reduces pulmonary and cerebral edema incidence, and significantly extends the golden period for UHS at high altitudes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40635-025-00833-w","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T23:01:57Z","timestamp":1766098917000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["4-Phenylbutyric acid extends the gold time of uncontrolled hemorrhagic shock at high altitude by alleviating vital organ injury"],"prefix":"10.1186","volume":"13","author":[{"given":"Jie","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Yong","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing-Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Ming","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-Qun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-Sen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao-Yue","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang-Ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"833_CR1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S0140-6736(22)00887-X","volume":"400","author":"JA Razzak","year":"2022","unstructured":"Razzak JA, Bhatti J, Wright K, Nyirenda M, Tahir MR, Hyder AA (2022) Improvement in trauma care for road traffic injuries: an assessment of the effect on mortality in low-income and middle-income countries. 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