Lung microvascular permeability to dextran in alpha-naphthylthiourea-induced edema. Sites of filtration, patterns of accumulation, and effects of fixation.

The detailed topography of filtration and of accumulation of the tracer dextran 75 was studied in 3 control dogs and in 9 experimental dogs in which edema was induced with 27 mg/kg alpha-naphthylthiourea. When moderately severe edema was present, 15-20 ml/kg of 6% dextran 75 was infused over 10-15 minutes; lung lobes were then fixed immediately by immersion, airway instillation, or vascular perfusion with 5% glutaraldehyde, 3% paraformaldehyde, or by freeze-substitution. For light microscopy, sections were embedded in methacrylate and stained with periodic acid-Schiff; for electron microscopy, they were embedded in Epon. The tracer was confined to the vasculature in controls. In all but one animal with edema, the tracer was seen in relation to capillaries, nonmuscular and partly muscular arteries, and veins, not in the walls of muscular arteries or around bronchial vessels. The dextran rapidly entered alveoli, lymphatics, and the interstitium around small vessels; there was much less tracer in the interstitium around larger vessels and essentially none around airways, consistent with the notion the interstitium acts as a sequestered pool. Furthermore, it was found that significant artifacts resulted from airway instillation and vascular perfusion fixation.