Interactive effects of mechanical ventilation and kidney health on lung function in an in vivo mouse model.
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.
Dodd-O
Jeffrey M
JM
Anesthesiology/Critical Care Medicine, Johns Hopkins Hospital, Meyer 297A, 600 N. Wolfe St., Baltimore, MD 21287-8106, USA. jdoddo@jhmi.edu
Hristopoulos
Maria
M
Scharfstein
Daniel
D
Brower
Roy
R
Hassoun
Paul
P
King
Landon S
LS
Becker
Patrice
P
Liu
Manchang
M
Wang
Weiwei
W
Hassoun
Heitham T
HT
Rabb
Hamid
H
D000208:Acute Disease; D055371:Acute Lung Injury / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002245:Carbon Dioxide / Q000097:blood; D004396:Coloring Agents / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005070:Evans Blue / Q000493:pharmacokinetics; D007674:Kidney Diseases / Q000150:complications* / Q000503:physiopathology*; D008214:Lymphocytes / Q000473:pathology; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000097:blood; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods*; D012720:Severity of Illness Index; D013047:Specific Pathogen-Free Organisms; D013990:Tidal Volume
D004396:Coloring Agents; D002245:Carbon Dioxide; D005070:Evans Blue; D010100:Oxygen