{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:56:13Z","timestamp":1753890973866,"version":"3.41.2"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>We previously demonstrated marked lung-protective properties of 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>, STS) in a blinded, randomized, controlled, long-term, resuscitated porcine model of swine with coronary artery disease, i.e., with decreased expression of the H<jats:sub>2<\/jats:sub>S-producing enzyme cystathionine-\u03b3-lyase (CSE). We confirmed these beneficial effects of STS by attenuation of lung, liver and kidney injury in mice with genetic CSE deletion (CSE-ko) undergoing trauma-and-hemorrhage and subsequent intensive care-based resuscitation. However, we had previously also shown that any possible efficacy of a therapeutic intervention in shock states depends both on the severity of shock as well as on the presence or absence of chronic underlying co-morbidity. Therefore, this prospective, randomized, controlled, blinded experimental study investigated the effects of the STS in cardiovascular healthy swine. After anesthesia and surgical instrumentation, 17 adult Bretoncelles-Meishan-Willebrand pigs were subjected to 3 hours of hemorrhage by removal of 30% of the blood volume and titration of the mean arterial pressure (MAP) \u2248 40 \u00b1 5 mmHg. Afterwards, the animals received standardized resuscitation including re-transfusion of shed blood, fluids, and, if needed, continuous i.v. noradrenaline to maintain MAP at pre-shock values. Animals were randomly allocated to either receive Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> or vehicle control starting 2 hours after initiation of shock until 24 hours of resuscitation. The administration of Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> did not alter survival during the observation period of 68 hours after the initiation of shock. No differences in cardio-circulatory functions were noted despite a significantly higher cardiac output, which coincided with significantly more pronounced lactic acidosis at 24 hours of resuscitation in the Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> group. Parameters of liver, lung, and kidney function and injury were similar in both groups. However, urine output was significantly higher in the Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> group at 24 hours of treatment. Taken together, this study reports no beneficial effect of Na<jats:sub>2<\/jats:sub>S<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> in a clinically relevant model of hemorrhagic shock-and-resuscitation in animals without underlying chronic cardiovascular co-morbidity.<\/jats:p>","DOI":"10.3389\/fimmu.2022.901005","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T04:27:41Z","timestamp":1655353661000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["The H2S Donor Sodium Thiosulfate (Na2S2O3) Does Not Improve Inflammation and Organ Damage After Hemorrhagic Shock in Cardiovascular Healthy Swine"],"prefix":"10.3389","volume":"13","author":[{"given":"David Alexander 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