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The H<jats:sub>2<\/jats:sub>S donor sodium thiosulfate (Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>) is a recognized drug devoid of major side effects, and, hence, we determined its effects in our full scale ICU-model of resuscitated murine trauma-and-hemorrhage. We hypothesized that Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> might improve energy metabolism and thereby exert organ-protective effects as previously demonstrated in animals with genetic cystathionine-\u03b3-lyase (CSE) deletion (CSE<jats:sup>\u2212\/\u2212<\/jats:sup>).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>30 mice underwent combined blast wave-induced blunt chest trauma followed by 1\u00a0h of hemorrhagic shock (mean arterial pressure MAP\u2009=\u200935\u2009\u00b1\u20095\u00a0mmHg). Thereafter, resuscitation was initiated comprising re-transfusion of shed blood, lung-protective mechanical ventilation, fluid resuscitation and continuous i.v. noradrenaline infusion to maintain MAP\u2009&gt;\u200955\u00a0mmHg over 6\u00a0h, and randomized administration of either i.v. 0.45\u00a0mg\/g<jats:sub>bodyweight<\/jats:sub> Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> or vehicle (NaCl 0.9%). Hemodynamics, lung mechanics, gas exchange, acid\u2013base-status and organ function parameters were recorded. Metabolic pathways were quantified based on gas chromatography\/mass spectrometry assessment of plasma isotope enrichment during primed-continuous infusion of stable, non-radioactive, isotope labeled substrates. Mitochondrial function was determined using high-resolution respirometry, and tissue target proteins (nitrotyrosine formation, extravascular albumin accumulation, CSE expression) were analyzed using immunohistochemistry.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Data originate from 23 mice (Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\n              <jats:italic>n<\/jats:italic>\u2009=\u200912; vehicle <jats:italic>n<\/jats:italic>\u2009=\u200911)<jats:sub>.<\/jats:sub> Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> affected neither survival nor noradrenaline requirements. While minute ventilation had to be increased over time in both groups to maintain arterial PCO<jats:sub>2<\/jats:sub> without intergroup difference, arterial PO<jats:sub>2<\/jats:sub> decreased over time in Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>-treated mice (<jats:italic>p<\/jats:italic>\u2009=\u20090.006). Although arterial pH decreased in both groups (vehicle <jats:italic>p<\/jats:italic>\u2009=\u20090.049; Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\n              <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), metabolic acidosis was more pronounced in the Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> group. Neither metabolic pathways nor tissue mitochondrial respiratory activity or tissue target proteins showed any intergroup differences.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Discussion<\/jats:title>\n            <jats:p>In this model of resuscitated trauma-and-hemorrhage, Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> did not exert any beneficial metabolic or organ-protective effect and was even associated with impaired pulmonary function. These results are in contrast to our previous findings in CSE<jats:sup>\u2212\/\u2212<\/jats:sup> mice, but in line with more recent findings in CSE<jats:sup>\u2212\/\u2212<\/jats:sup> mice with pre-existing comorbidities. Hence, our studies do not support a beneficial role of Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> in trauma resuscitation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40635-025-00778-0","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T14:21:08Z","timestamp":1754490068000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5428-3339","authenticated-orcid":false,"given":"Maximilian","family":"Feth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirabel","family":"Gracco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Gr\u00f6ger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Hogg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Kress","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Calzia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Wachter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Radermacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Merz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"issue":"6","key":"778_CR1","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1007\/s10753-024-02106-2","volume":"47","author":"Y Li","year":"2024","unstructured":"Li Y, Qin K, Liang W, Yan W, Fragoulis A, Pufe T et al (2024) Kidney injury in a murine hemorrhagic shock\/resuscitation model is alleviated by sulforaphane\u2019s anti-inflammatory and antioxidant action. 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