{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:41:13Z","timestamp":1788972073467,"version":"build-2803163510"},"reference-count":50,"publisher":"Portland Press Ltd.","issue":"8","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4,25]]},"abstract":"<jats:p>Statins may offer protective effects in sepsis through anti-inflammatory, mitochondrial protection and other actions. We thus evaluated the effects of simvastatin on survival, organ and mitochondrial function, tissue and plasma ubiquinone levels and liver transcriptomics in a 3-day rat model of sepsis. Comparisons of rat plasma simvastatin and ubiquinone levels were made against levels sampled in blood from patients with acute lung injury (ALI) enrolled into a trial of statin therapy. Animals received simvastatin by gavage either pre- or post-induction of faecal peritonitis. Control septic animals received vehicle alone. Seventy-two-hour survival was significantly greater in statin pre-treated animals (43.7%) compared with their statin post-treated (12.5%) and control septic (25%) counterparts (P&amp;lt;0.05). Sepsis-induced biochemical derangements in liver and kidney improved with statin therapy, particularly when given pre-insult. Both simvastatin pre- and post-treatment prevented the fall in mitochondrial oxygen consumption in muscle fibres taken from septic animals at 24\u00a0h. This beneficial effect was paralleled by recovery of genes related to fatty acid metabolism. Simvastatin pre-treatment resulted in a significant decrease in myocardial ubiquinone. Patients with ALI had a marked variation in plasma simvastatin acid levels; however, their ubiquinone\/low-density lipoprotein (LDL) cholesterol ratio did not differ regardless of whether they were receiving statin or placebo. In summary, despite protective effects seen with statin treatment given both pre- and post-insult, survival benefit was only seen with pre-treatment, reflecting experiences in patient studies.<\/jats:p>","DOI":"10.1042\/cs20160802","type":"journal-article","created":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T01:50:16Z","timestamp":1487209816000},"page":"747-758","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Simvastatin pre-treatment improves survival and mitochondrial function in a 3-day fluid-resuscitated rat model of sepsis"],"prefix":"10.1042","volume":"131","author":[{"given":"Jerome","family":"Morel","sequence":"first","affiliation":[{"name":"Departement d'anesthesie et reanimation, CHU Saint Etienne, Saint Etienne, France"},{"name":"Bloomsbury Institute of Intensive Care Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Hargreaves","sequence":"additional","affiliation":[{"name":"Neurometabolic Unit, National Hospital, Queen Square, London, WC1N 3BG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brealey","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viruna","family":"Neergheen","sequence":"additional","affiliation":[{"name":"Neurometabolic Unit, National Hospital, Queen Square, London, WC1N 3BG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne\u00a0T.","family":"Backman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Lindig","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Therapy and Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Bl\u00e4ss","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Therapy and Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Therapy and Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel\u00a0F.","family":"McAuley","sequence":"additional","affiliation":[{"name":"Centre for Infection and Immunity, Queen's University of Belfast and Regional Intensive Care Unit, Royal Victoria Hospital, Belfast, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervyn","family":"Singer","sequence":"additional","affiliation":[{"name":"Bloomsbury Institute of Intensive Care Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2017,4,6]]},"reference":[{"key":"2021113011073153600_B1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0140-6736(06)68041-0","article-title":"Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis","volume":"367","author":"Hackam","year":"2006","journal-title":"Lancet"},{"key":"2021113011073153600_B2","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00134-005-2859-y","article-title":"Statin therapy is associated with fewer deaths in patients with bacteraemia","volume":"32","author":"Kruger","year":"2006","journal-title":"Intensive Care Med."},{"key":"2021113011073153600_B3","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1086\/323334","article-title":"The effect of statins on mortality in patients with bacteremia","volume":"33","author":"Liappis","year":"2001","journal-title":"Clin. 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