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Critical Care Research and Practice
Volume 2011, Article ID 217896, 11 pages
http://dx.doi.org/10.1155/2011/217896
Research Article

Plasminogen Activator Inhibitor-Type I Gene Deficient Mice Show Reduced Influx of Neutrophils in Ventilator-Induced Lung Injury

1Department of Anesthesiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
2Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
3Department of Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
4Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
5Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
6Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
7HERMES Critical Care Group, Amsterdam, The Netherlands

Received 28 February 2011; Revised 15 May 2011; Accepted 17 May 2011

Academic Editor: Peter J. Papadakos

Copyright © 2011 Esther K. Wolthuis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ventilator-induced lung injury (VILI) is associated with inhibition of the fibrinolytic system secondary to increased production of plasminogen activator inhibitor- (PAI-)1. To determine the role of PAI-1 on pulmonary coagulopathy and inflammation during mechanical ventilation, PAI-1 gene-deficient mice and their wild-type littermates were anesthetized (control), or anesthetized, tracheotomized and subsequently ventilated for 5 hours with either low tidal volumes ( L V T ) or high tidal volumes ( H V T ). VILI was assessed by pulmonary coagulopathy, lung wet-to-dry ratios, total protein level in bronchoalveolar lavage fluid, neutrophil influx, histopathology, and pulmonary and plasma cytokine levels. Ventilation resulted in pulmonary coagulopathy and inflammation, with more injury following ventilation with H V T as compared to L V T . In PAI-1 gene-deficient mice, the influx of neutrophils in the pulmonary compartment was attenuated, while increased levels of pulmonary cytokines were found. Other endpoints of VILI were not different between PAI-1 gene-deficient and wild-type mice. These data indicate that a defect fibrinolytic response attenuates recruitment of neutrophils in VILI.