Time and pressure dependence of transvascular Clara cell protein, albumin, and IgG transport during ventilator-induced lung injury in mice

We compared the transport of three proteins with different hydrodynamic radii with ultrastructural changes in lungs of intact mice ventilated at peak inflation pressures (PIP) of 15, 35, 45, and 55 cmH2O for 2 h and PIP of 55 cmH2O for 0.5 and 1 h. After 2 h of ventilation, significant increases were observed in plasma Clara cell secretory protein (1.9 nm radius) at 35 cmH2O PIP and in bronchoalveolar lavage fluid albumin (3.6 nm radius) at 45 cmH2O PIP and IgG (5.6 nm radius) at 55 cmH2O PIP. Increased concentrations of all three proteins and lung wet-to-dry weight ratios were significantly correlated with PIP and ventilation time. Clara cell secretory protein and albumin increased significantly after 0.5 h of 55 cmH2O PIP, but IgG increased only after 2 h. Separation of endothelium or epithelium to form blebs was apparent only in small vessels (15-30 μm diameter) at 45 cmH2O PIP and after 0.5 h at 55 cmH2O PIP but became extensive after 2 h of ventilation at 55 cmH2O PIP. Junctional gaps between cells were rarely observed. Ultrastructural lung injury and protein clearances across the air-blood barrier were related to ventilation time and PIP levels. Protein clearances increased in relation to molecular size, consistent with increasing dimensions and frequency of transmembrane aqueous pathways.