Ventilator-associated lung injury decreases lung ability to clear edema in rats

Ventilator-associated lung injury (VALI) is caused by high tidal volume (VT) excursions producing microvascular leakage and pulmonary edema. However, the effects of VALI on lung edema clearance and alveolar epithelial cells' Na,K-ATPase function have not been elucidated. We studied lung edema clearance in the isolated-perfused rat lung model after ventilation for 25, 40, and 60 min with high Vr (peak airway opening pressure [Pao] of approximately 35 cm H2O) and compared them with low Vr ventilation (Pao similar to 8 cm H2O), moderate VT ventilation (Pao similar to 20 cm H2O), and nonventilated rats. Lung edema clearance in control rats was 0.50 +/- 0.02 ml/h and decreased after 40 and 60 min of high VT to 0.26 +/- 0.03 and 0.11 +/- 0.08 ml/h, respectively (p < 0.01), but did not change after low Vr and moderate VT ventilation at any time point. Lung permeability to small (Na-22(+), [H-3]mannitol) and large solutes (fluorescein isothiocyanate-tagged albumin [FITC-albumin]) increased significantly in rats ventilated for 60 min with high VT, compared with low VT, moderate VT, and control rats (p < 0.01). Paralleling the impairment in lung edema clearance we found a decrease in Na,K-ATPase activity in alveolar type ii (ATII) cells isolated from rats ventilated with moderate VT and high VT for 40 min without changes in alpha 1 Na,K-ATPase mRNA. We reason that VALI decreases lung ability to clear edema by inhibiting active sodium transport and Na,K-ATPase function in the alveolar epithelium.