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

Departments of ¹Physiology and ²Pathology and ³Center for Lung Biology, College of Medicine, University of South Alabama, Mobile, Alabama 36688; and ⁴Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Submitted 21 August 2003 ; accepted in final form 8 November 2003

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.

vascular permeability; acute respiratory distress syndrome; bronchoalveolar lavage; pulmonary edema

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