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1 Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States
2 Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institution, Baltimore, Maryland, United States; United States
3 Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
4 Medicine, Johns Hopkins University, Baltimore, Maryland, United States
5 Johns Hopkins University, United States
6 Medicine-renal, Johns Hopkins University, Baltimore, Maryland, United States
7 Surgery, Johns Hopkins, Baltimore, Maryland, United States
8 Medicine/Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
* To whom correspondence should be addressed. E-mail: jdoddo{at}jhmi.edu.
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. C57BL6 mice underwent AKI (30 min kidney ischemia) or sham surgery, followed at 24 hr by 4 hrs spontaneously breathing (SB), mechanical ventilation with low tidal volume (7 ml/kg, LTV), or mechanical ventilation with high tidal volume (30 ml/kg, HTV). Compared to LTV, median bronchial alveolar lavage (BAL) protein leak was signifianctly lower with SB and greater with HTV in both sham and AKI mice. Compared to 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 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 MV 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.
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