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Am J Physiol Lung Cell Mol Physiol 280: L896-L904, 2001;
1040-0605/01 $5.00
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Vol. 280, Issue 5, L896-L904, May 2001

Alveolar epithelial barrier functions in ventilated perfused rabbit lungs

Hossein Ardeschir Ghofrani, Markus Gerhard Kohstall, Norbert Weissmann, Thomas Schmehl, Ralph Theo Schermuly, Werner Seeger, and Friedrich Grimminger

Department of Internal Medicine, Justus-Liebig-University Giessen, 35385 Giessen, Germany

We employed ultrasonic nebulization for homogeneous alveolar tracer deposition into ventilated perfused rabbit lungs. 22Na and 125I-albumin transit kinetics were monitored on-line with gamma detectors placed around the lung and the perfusate reservoir. [3H]mannitol was measured by repetitive counting of perfusion fluid samples. Volume of the alveolar epithelial lining fluid was estimated with bronchoalveolar lavage with sodium-free isosmolar mannitol solutions. Sodium clearance rate was -2.2 ± 0.3%/min. This rate was significantly reduced by preadministration of ouabain/amiloride and enhanced by pretreatment with aerosolized terbutaline. The 125I-albumin clearance rate was -0.40 ± 0.05%/min. The appearance of [3H]mannitol in the perfusate was not influenced by ouabain/amiloride or terbutaline but was markedly enhanced by pretreatment with aerosolized protamine. An epithelial lining fluid volume of 1.22 ± 0.21 ml was calculated in control lungs. Fluid absorption rate was 1.23 µl · g lung weight-1 · min-1, which was blunted after pretreatment with ouabain/amiloride. We conclude that alveolar tracer loading by aerosolization is a feasible technique to assess alveolar epithelial barrier properties in aerated lungs. Data on active and passive sodium flux, paracellular solute transit, and net fluid absorption correspond well to those in previous studies in fluid-filled lungs; however, albumin clearance rates were markedly higher in the currently investigated aerated lungs.

amiloride; epithelial lining fluid; ion channel; ouabain; protamine; protein clearance


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