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Am J Physiol Lung Cell Mol Physiol 287: L402-L410, 2004. First published April 23, 2004; doi:10.1152/ajplung.00435.2003
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Effect of lung-protective ventilation on severe Pseudomonas aeruginosa pneumonia and sepsis in rats

Kiyoyasu Kurahashi,1 Shuhei Ota,1 Kyota Nakamura,1 Yoji Nagashima,2 Takuya Yazawa,3 Minako Satoh,1 Asako Fujita,1 Ritsuko Kamiya,1 Eri Fujita,1 Yasuko Baba,1 Kanji Uchida,1 Naoto Morimura,1 Tomio Andoh,1 and Yoshitsugu Yamada1

Departments of 1Anesthesiology and Critical Care Medicine, 2Molecular Pathology and Oncology, and 3Cellular Pathobiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan 236-0004

Submitted 5 December 2003 ; accepted in final form 19 April 2004

Pneumonia caused by Pseudomonas aeruginosa carries a high rate of morbidity and mortality. A lung-protective strategy using low tidal volume (VT) ventilation for acute lung injury improves patient outcomes. The goal of this study was to determine whether low VT ventilation has similar utility in severe P. aeruginosa infection. A cytotoxic P. aeruginosa strain, PA103, was instilled into the left lung of rats anesthetized with pentobarbital. The lung-protective effect of low VT (6 ml/kg) with or without high positive end-expiratory pressure (PEEP, 10 or 3 cmH2O) was then compared with high VT with low PEEP ventilation (VT 12 ml/kg, PEEP 3 cmH2O). Severe lung injury and septic shock was induced. Although ventilatory mode had little effect on the involved lung or septic physiology, injury to noninvolved regions was attenuated by low VT ventilation as indicated by the wet-to-dry weight ratio (W/D; 6.13 ± 0.78 vs. 3.78 ± 0.26, respectively) and confirmed by histopathological examinations. High PEEP did not yield a significant protective effect (W/D, 4.03 ± 0.32) but, rather, caused overdistension of noninvolved lungs. Bronchoalveolar lavage revealed higher concentrations of TNF-{alpha} in the fluid of noninvolved lung undergoing high VT ventilation compared with those animals receiving low VT. We conclude that low VT ventilation is protective in noninvolved regions and that the application of high PEEP attenuated the beneficial effects of low VT ventilation, at least short term. Furthermore, low VT ventilation cannot protect the involved lung, and high PEEP did not significantly alter lung injury over a short time course.

acute lung injury; ventilator-induced lung injury; lung protective strategy; cytokines; bacterial toxins



Address for reprint requests and other correspondence: K. Kurahashi, 3-9, Fukuura, Kanazawa-ku, Yokohama, Japan, 236-0004 (E-mail: kiyok{at}med.yokohama-cu.ac.jp)




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