{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:50:49Z","timestamp":1792029049752,"version":"4.4.0"},"reference-count":80,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health & Medical Research Council","doi-asserted-by":"publisher","award":["GNT2019948"],"award-info":[{"award-number":["GNT2019948"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001786","name":"The University of Adelaide","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001786","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Septic shock has an unacceptably high mortality rate and unmet need for new therapeutics. Murine models are crucial for research, yet methodologies often differ. This study characterised standard- and high-grade caecal ligation and puncture (CLP) murine models of septic shock by integrating ultraminiature arterial telemetry with comprehensive plasma biomarker analysis. Standard-grade and high-grade CLP was performed in 8\u201310 week old, male C57BL\/6 mice (n = 98), with a subset implanted with arterial telemetry to monitor real-time circulatory function. Plasma markers of inflammation and organ damage were measured at multiple intervals up to 168 h post-CLP. Standard-grade and high-grade CLP showed distinct progressions; episodes of hypotension began 5\u20136 h after CLP in 30% of standard-grade and all high-grade CLP mice, with respective 168 h mortality of 40% and 71%. Recurrent episodes of hypotension 5\u201339 h after CLP were universally lethal. The coincidence of hypotension and elevated plasma lactate defined the onset of septic shock after high-grade CLP, which was always lethal. Inflammatory cytokines and markers of liver, renal, and cardiac damage were markedly elevated to 168 h after high-grade CLP, in contrast to standard-grade CLP, which returned to baseline by 48 h. Elevated plasma IL-6, TNF\u03b1, and corticosterone, along with reduced albumin, were significantly correlated with mortality. In conclusion, this research refines murine CLP models by providing a precise, dynamic map of the progression to septic shock. The high-grade CLP model consistently models early and late-stage physiological deterioration and serves as a robust model for evaluating the efficacy of novel therapies aimed at human septic shock.<\/jats:p>","DOI":"10.3390\/ijms26209954","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:13:03Z","timestamp":1760717583000},"page":"9954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Precision Profiling of Disease Progression in Murine Models of Sepsis and Septic Shock"],"prefix":"10.3390","volume":"26","author":[{"given":"Stewart D.","family":"Ramsay","sequence":"first","affiliation":[{"name":"Intestinal Sensing Group, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Diabetes, Nutrition & Gut Health, Lifelong Health, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Declan E.","family":"Kilgariff","sequence":"additional","affiliation":[{"name":"Intestinal Sensing Group, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5942-2150","authenticated-orcid":false,"given":"Benjamin J.","family":"Young","sequence":"additional","affiliation":[{"name":"Intestinal Sensing Group, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9640-1911","authenticated-orcid":false,"given":"Mark P.","family":"Plummer","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marni A.","family":"Nenke","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7450-5808","authenticated-orcid":false,"given":"Emily J.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Torpy","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5116-4951","authenticated-orcid":false,"given":"Richard L.","family":"Young","sequence":"additional","affiliation":[{"name":"Intestinal Sensing Group, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Adelaide Medical School, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Diabetes, Nutrition & Gut Health, Lifelong Health, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, SA 5000, Australia"},{"name":"Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","first-page":"13","article-title":"Sepsis and septic shock","volume":"7","author":"Cecconi","year":"2018","journal-title":"Lancet"},{"key":"ref_2","first-page":"67","article-title":"Sepsis Definition: What\u2019s New in the Treatment Guidelines","volume":"61","author":"Srzic","year":"2022","journal-title":"Acta Clin. 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