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However, particularly in pre-injured lungs, even protective ventilation strategies may evoke ventilator-induced lung injury (VILI), which is characterized by pulmonary inflammation and vascular leakage. Adjuvant pharmacologic strategies in addition to lung protective ventilation to attenuate VILI are lacking. Simvastatin exhibited anti-inflammatory and endothelial barrier stabilizing properties <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Mice were ventilated (12 ml\/kg; six hours) and subjected to simvastatin (20 mg\/kg) or sham treatment. Pulmonary microvascular leakage, oxygenation, pulmonary and systemic neutrophil and monocyte counts and cytokine release in lung and blood plasma were assessed. Further, lung tissue was analyzed by electron microscopy.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Mechanical ventilation induced VILI, displayed by increased pulmonary microvascular leakage and endothelial injury, pulmonary recruitment of neutrophils and Gr-1<jats:sup>high<\/jats:sup> monocytes, and by liberation of inflammatory cytokines in the lungs. Further, VILI associated systemic inflammation characterized by blood leukocytosis and elevated plasma cytokines was observed. Simvastatin treatment limited pulmonary endothelial injury, attenuated pulmonary hyperpermeability, prevented the recruitment of leukocytes to the lung, reduced pulmonary cytokine levels and improved oxygenation in mechanically ventilated mice.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>High-dose simvastatin attenuated VILI in mice by reducing MV-induced pulmonary inflammation and hyperpermeability.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/cc9209","type":"journal-article","created":{"date-parts":[[2010,7,30]],"date-time":"2010-07-30T18:59:45Z","timestamp":1280516385000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Simvastatin attenuates ventilator-induced lung injury in mice"],"prefix":"10.1186","volume":"14","author":[{"given":"Holger C","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Hellwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Rosseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tschernig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schmiedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitt","family":"Gutbier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Schmeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hippenstiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harm","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Morawietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Suttorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Witzenrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,7,30]]},"reference":[{"key":"8616_CR1","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1001\/jama.287.3.345","volume":"287","author":"A Esteban","year":"2002","unstructured":"Esteban A, Anzueto A, Frutos F, Alia I, Brochard L, Stewart TE, Benito S, Epstein SK, Apezteguia C, Nightingale P, Arroliga AC, Tobin MJ: Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study.\n                           JAMA 2002, 287: 345-355. 10.1001\/jama.287.3.345","journal-title":"JAMA"},{"key":"8616_CR2","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/labinvest.3700440","volume":"86","author":"S Dhanireddy","year":"2006","unstructured":"Dhanireddy S, Altemeier WA, Matute-Bello G, O'Mahony DS, Glenny RW, Martin TR, Liles WC: Mechanical ventilation induces inflammation, lung injury, and extra-pulmonary organ dysfunction in experimental pneumonia.\n                           Lab Invest 2006, 86: 790-799. 10.1038\/labinvest.3700440","journal-title":"Lab Invest"},{"key":"8616_CR3","doi-asserted-by":"publisher","first-page":"R136","DOI":"10.1186\/cc5050","volume":"10","author":"DS O'Mahony","year":"2006","unstructured":"O'Mahony DS, Liles WC, Altemeier WA, Dhanireddy S, Frevert CW, Liggitt D, Martin TR, Matute-Bello G: Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction.\n                           Crit Care 2006, 10: R136. 10.1186\/cc5050","journal-title":"Crit Care"},{"key":"8616_CR4","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/j.1475-097X.2007.00722.x","volume":"27","author":"SJ Verbrugge","year":"2007","unstructured":"Verbrugge SJ, Lachmann B, Kesecioglu J: Lung protective ventilatory strategies in acute lung injury and acute respiratory distress syndrome: from experimental findings to clinical application.\n                           Clin Physiol Funct Imaging 2007, 27: 67-90. 10.1111\/j.1475-097X.2007.00722.x","journal-title":"Clin Physiol Funct Imaging"},{"key":"8616_CR5","doi-asserted-by":"crossref","unstructured":"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. 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