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Am J Physiol Lung Cell Mol Physiol 296: L3-L11, 2009. First published October 10, 2008; doi:10.1152/ajplung.00030.2008
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EDITORIAL FOCUS

Interactive effects of mechanical ventilation and kidney health on lung function in an in vivo mouse model

Jeffrey M. Dodd-o,1 Maria Hristopoulos,1 Daniel Scharfstein,2 Roy Brower,4 Paul Hassoun,4 Landon S. King,4 Patrice Becker,4 Manchang Liu,3 Weiwei Wang,2 Heitham T. Hassoun,5 and Hamid Rabb3

Departments of 1Anesthesiology and Critical Care Medicine, 2Biostatistics, Johns Hopkins Bloomberg School of Public Health, 3Medicine, Division of Nephrology, 4Medicine, Division of Pulmonary and Critical Care Medicine, and 5Surgery, Division of Vascular Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Submitted 15 January 2008 ; accepted in final form 2 October 2008

We hypothesized that the influence of acute kidney injury (AKI) on the sensitivity of the lung to an injurious process varies with the severity of the injurious process. Thus, we thought that AKI would exacerbate lung injury from low degrees of lung trauma but attenuate lung injury from higher degrees of lung trauma. C57BL/6 mice underwent AKI (30-min kidney ischemia) or sham surgery, followed at 24 h by 4 h of spontaneous breathing (SB), mechanical ventilation with low tidal volume (7 ml/kg, LTV), or mechanical ventilation with high tidal volume (30 ml/kg, HTV). Compared with LTV, median bronchoalveolar lavage (BAL) protein leak was significantly lower with SB and greater with HTV in both sham and AKI mice. Compared with LTV, median Evans blue dye-labeled albumin extravasation in lungs (L-EBD) was also significantly lower with SB and greater with HTV. L-EBD showed a significant interaction between ventilatory mode and kidney health, such that AKI attenuated the L-EBD rise seen in HTV vs. LTV sham mice. An interaction between ventilatory mode and kidney health could also be seen in BAL neutrophil number (PMN). Thus, AKI attenuated the BAL PMN rise seen in HTV vs. LTV sham mice. These data support the presence of a complex interaction between mechanical ventilation and AKI in which the sensitivity of the lung to trauma varies with the magnitude of the trauma and may involve a modification of pulmonary neutrophil activity by AKI.

acute kidney injury; Evans blue dye



Address for reprint requests and other correspondence: J. M. Dodd-o, Anesthesiology/Critical Care Medicine, Johns Hopkins Hospital, Meyer 297A, 600 N. Wolfe St., Baltimore, MD 21287-8106 (e-mail: jdoddo{at}jhmi.edu)




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