Statin treatment after onset of sepsis in a murine model improves survival.
Abstract
Background— HMG-CoA-reductase inhibitors have been shown to exhibit pronounced immunomodulatory effects independent of lipid lowering. We have recently demonstrated that pretreatment with simvastatin profoundly improves survival in a cecal ligation and perforation (CLP) model of sepsis. Here, we studied whether treatment with simvastatin after onset of sepsis-induced hemodynamic alterations is beneficial and whether prolonged survival can also be achieved with other statins. Methods and Results— Mice were rendered septic by CLP. At 6 hours after sepsis induction, when profound hemodynamic alterations were manifest, treatment with atorvastatin, fluvastatin, pravastatin, simvastatin, or placebo was initiated. Except for fluvastatin (27±2.3 hours), survival time was extended from 23±1.2 hours for placebo-treated mice to 37±3.6 hours for simvastatin-treated, to 40±4.2 hours for atorvastatin-treated, and to 39±3.9 hours for pravastatin-treated mice. This profound improvement is based on the preservation of cardiac function and hemodynamic status in statin-treated animals, both of which are severely impaired in untreated CLP mice. As underlying mechanisms, improved susceptibility to endothelial nitric oxide synthase stimulation and reduced endothelial adhesion of leukocytes could be demonstrated after statin treatment. Conclusions— Well established in the treatment of lipid disorders and coronary artery disease, statins harbor the additional and novel potential of effective sepsis treatment. This benefit extends to several but not all statins tested.
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In murine models, statins improve animal survival rates after septic shock induced by LPS challenge, bacterial infection, or cecal ligation and puncture.
“In murine models (Merx et al., 2005; Yasuda et al., 2006; Chaudhry et al., 2008; Rosch et al., 2010; Shinozaki et al., 2010), statins appeared to improve animal survival rates after septic shock induced by LPS challenge, bacterial infection or cecal ligation and puncture”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Merx et al., 2005
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- Authors
- Merx, M. W., Liehn, E. A., Graf, J., van de Sandt, A., Schaltenbrand, M., Schrader, J., Hanrath, P., & Weber, C.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- From Medizinische Klinik I (M.W.M., J.G., A. vd S., M.S., P.H., C.W.) and Kardiovaskuläre Molekularbiologie (E.A.L., C.W.), RWTH Aachen, and Institut für Herz- und Kreislaufphysiologie (J.S.), Heinrich-Heine-Universität, Düsseldorf, Germany.
- Venue
- Circulation
- Published
- 2005-07-05
- Volume
- 112
- Issue
- 1
- Pages
- 117-124
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2044322051
- Cited by
- 287
- References
- 38
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 11 · 2015: 15 · 2014: 17 · 2013: 19 · 2012: 27
- FWCI
- 15.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- sepsis, statins, simvastatin, atorvastatin, pravastatin, fluvastatin, cecal ligation and puncture, immunomodulation, cardiac function, hemodynamics, endothelial nitric oxide synthase, leukocyte adhesion, survival
- MeSH terms
- Animals, Cardiac Output, Cell Adhesion, Cells, Cultured, Disease Models, Animal, Echocardiography, Endothelium, Vascular, Hemodynamics, Leukocytes, Male, Mice, Inbred C57BL, Survival Rate, Sepsis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Mice, Nitric Oxide Synthase Type III
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