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Critical Care
Published in: Critical Care 4/2010

Open Access 01-08-2010 | Research

Simvastatin attenuates ventilator-induced lung injury in mice

Authors: Holger C Müller, Katharina Hellwig, Simone Rosseau, Thomas Tschernig, Andreas Schmiedl, Birgitt Gutbier, Bernd Schmeck, Stefan Hippenstiel, Harm Peters, Lars Morawietz, Norbert Suttorp, Martin Witzenrath

Published in: Critical Care | Issue 4/2010

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Abstract

Introduction

Mechanical ventilation (MV) is a life saving intervention in acute respiratory failure without alternative. 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 in vitro and in vivo.

Methods

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.

Results

Mechanical ventilation induced VILI, displayed by increased pulmonary microvascular leakage and endothelial injury, pulmonary recruitment of neutrophils and Gr-1high 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.

Conclusions

High-dose simvastatin attenuated VILI in mice by reducing MV-induced pulmonary inflammation and hyperpermeability.
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Metadata
Title
Simvastatin attenuates ventilator-induced lung injury in mice
Authors
Holger C Müller
Katharina Hellwig
Simone Rosseau
Thomas Tschernig
Andreas Schmiedl
Birgitt Gutbier
Bernd Schmeck
Stefan Hippenstiel
Harm Peters
Lars Morawietz
Norbert Suttorp
Martin Witzenrath
Publication date
01-08-2010
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2010
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc9209

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