Ventilator-associated lung injury decreases lung ability to clear edema inrats

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 cleara nce in the isolated-perfused rat lung model after ventilation for 25, 40, a nd 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 decr eased 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 [FIT C-albumin]) increased significantly in rats ventilated for 60 min with high VT, compared with low VT, moderate VT, and control rats (p < 0.01). Parall eling the impairment in lung edema clearance we found a decrease in Na,K-AT Pase activity in alveolar type ii (ATII) cells isolated from rats ventilate d with moderate VT and high VT for 40 min without changes in alpha 1 Na,K-A TPase mRNA. We reason that VALI decreases lung ability to clear edema by in hibiting active sodium transport and Na,K-ATPase function in the alveolar e pithelium.