{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:04:14Z","timestamp":1773399854960,"version":"3.50.1"},"reference-count":99,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DoD US Army Medical Research &amp; Development Command FY18 Broad Agency Announcement","award":["W81XWH190040\/BA180313"],"award-info":[{"award-number":["W81XWH190040\/BA180313"]}]},{"name":"DoD US Army Medical Research &amp; Development Command FY18 Broad Agency Announcement","award":["W81XWH200040\/PR190914"],"award-info":[{"award-number":["W81XWH200040\/PR190914"]}]},{"name":"DoD Congressionally Directed Medical Research Programs, Peer Reviewed Medical Research Program, Technology\/Therapeutic Development Award","award":["W81XWH190040\/BA180313"],"award-info":[{"award-number":["W81XWH190040\/BA180313"]}]},{"name":"DoD Congressionally Directed Medical Research Programs, Peer Reviewed Medical Research Program, Technology\/Therapeutic Development Award","award":["W81XWH200040\/PR190914"],"award-info":[{"award-number":["W81XWH200040\/PR190914"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven\u00ae resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. HS resulted in systemic and local complement activation, cytokine release, hypocoagulopathy, metabolic acidosis, MOF, and no animal survival. Resuscitation with LR and Voluven\u00ae after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the animals with hemorrhagic shock treated with Voluven\u00ae had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Hemorrhagic shock triggers early immunopathy and coagulopathy and appears associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.<\/jats:p>","DOI":"10.3390\/ijms25052500","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T04:23:10Z","timestamp":1708489390000},"page":"2500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Immunopathy and Coagulopathy on Multi-Organ Failure and Mortality in a Lethal Porcine Model of Controlled and Uncontrolled Hemorrhage"],"prefix":"10.3390","volume":"25","author":[{"given":"Milomir O.","family":"Simovic","sequence":"first","affiliation":[{"name":"US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA"},{"name":"The Geneva Foundation, Tacoma, WA 98402, USA"},{"name":"Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Bynum","sequence":"additional","affiliation":[{"name":"US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA"},{"name":"Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurandir J.","family":"Dalle Lucca","sequence":"additional","affiliation":[{"name":"US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8341-1539","authenticated-orcid":false,"given":"Yansong","family":"Li","sequence":"additional","affiliation":[{"name":"US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA"},{"name":"The Geneva Foundation, Tacoma, WA 98402, USA"},{"name":"Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/SHK.0000000000000096","article-title":"Challenges and Possibilities in Forward Resuscitation","volume":"41","author":"Hooper","year":"2014","journal-title":"Shock"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S0140-6736(12)61224-0","article-title":"Haemorrhage Control in Severely Injured Patients","volume":"380","author":"Gruen","year":"2012","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/ams2.426","article-title":"Complement and Coagulation Cascades in Trauma","volume":"6","author":"Satyam","year":"2019","journal-title":"Acute Med. 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