Notably, an upcoming randomized controlled NHLBI sponsored trial is going to investigate statin therapy in ALI (NCT00979121). As patients included in this trial will presumably receive respirator therapy, screening libraries the effects of statins on VILI observed in the current experimental study may possibly contribute to the outcome of the treatment arm.ConclusionsThis study shows, for the first time, that high-dose simvastatin markedly reduced VILI-associated microvascular leakage and improved pulmonary gas exchange in mechanically ventilated mice. Simvastatin prevented recruitment of PMN and Gr-1high monocytes to the lung, limited pulmonary cytokine production and attenuated endothelial injury in VILI. The data suggest that high-dose simvastatin offers a promising perspective to prevent VILI in addition to lung protective ventilation.
Key messages? Simvastatin improved microvascular leakage and improved oxygenation in VILI.? Simvastatin limited pulmonary hyperinflammation in VILI.? Simvastatin protected against VILI induced pulmonary endothelial injury.? Simvastatin offers a promising perspective to limit VILI in addition to lung protective ventilation.AbbreviationsALI: acute lung injury; ALT: Alanine transaminase; BAL: bronchoalveolar lavage; ELISA: enzyme-linked immuno sorbent assay; HMG COA: 3-hydroxy-3-methylglutaryl coenzyme A; HAS: human serum albumin; LPS: lipopolysacharide; MV: mechanical ventilation; PEEP: positive end-expiratory pressure; VILI: ventilator-induced lung injury; VT: tidal volume pressure.Competing interestsThe authors declare that they have no competing interests.
Authors’ contributionsHCM designed, coordinated and supervised all experiments, analysed the data and drafted the manuscript. KH and BG carried out the animal experiments and performed flow cytometry experiments. SR contributed to the design Carfilzomib of the experiments and drafted the manuscript. TT and AS performed electron microscopy and were responsible for image analysis. BS and SH carried out multiplex array experiments while HP performed cystatin C analysis and NS participated in drafting the manuscript. MW participated in the study design and drafted the manuscript.NotesSee related letter by Siempos et al., http://ccforum.com/content/14/5/441AcknowledgementsWe thank A. Santel for thoughtful discussion and useful advice and Andrea Schoenknecht for technical support.This study was supported in part by grants from the German Research Foundation to MW (OP 86/7-1) and SH (HI-789/6-1), and the German Federal Ministry of Education and Research to HCM, NS and SR (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis PROGRESS).
Respiratory tract infections are a serious threat to patients in ICUs [1,2].