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J Appl Physiol (October 20, 2005). doi:10.1152/japplphysiol.01060.2005
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Submitted on August 30, 2005
Accepted on October 18, 2005

Changes in lung permeability after chronic pulmonary artery obstruction

Elizabeth M. Wagner1*, Gulnura Karagulova1, John Jenkins1, John Bishai1, and Jessica McClintock1

1 Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Environmental Health Sciences, Johns Hopkins University, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: wagnerem{at}jhmi.edu.

We have shown that left pulmonary artery ligation (LPAL) in mice causes a prompt angiogenic response, with new systemic vessels from intercostal arteries penetrating the pleura within 6 days. Since angiogenic vessels in other organs have been shown to exhibit increased permeability, we studied vascular permeability (Evans blue dye extravasation, lung wet wt/dry wt, and lavaged protein) in naive C57Bl/6 mice and 4hrs, 14 and 21 days after LPAL (4-6 mice/time point). We also measured radiolabel clearance as an index of functional perfusion after LPAL. Tracer clearance from the left lung was maximal by 6 days after LPAL and not different from right lungs. Thus, a functional vasculature is established before 6 days of LPAL that results in normal tracer clearance. By 21 days after LPAL, Evans blue-albumin was significantly increased in the left lung relative to both 4 hrs (no vasculature) and 14 days after LPAL. Only after 21 days of LPAL, was left lung wet wt/dry wt significantly different from naive lungs. Additionally, lavaged protein was significantly increased both 4 hrs and 21 days after LPAL relative to control mice. Thus, using 3 different methods, results consistently demonstrated increased permeability to protein and water 21 days after LPAL. Although changes in surface area of perfusion might affect the interpretation of these results, blood flow measured with labeled microspheres indicated no change in left lung perfusion between 14 and 21 days of LPAL. Thus, the lung vasculature, remodeled as a consequence of chronic pulmonary artery obstruction, demonstrates increased water and protein permeability.







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