title: Lung and vascular function during chronic severe pulmonary ischemia.
abstract: Bronchial vascular angiogenesis takes place in a variety of lung inflammatory conditions such as asthma, cystic fibrosis, lung cancer, and chronic pulmonary thromboembolic disease. However, it is unclear whether neovascularization is predominantly appropriate and preserves lung tissue or whether it contributes further to lung pathology through edema formation and inflammation. In the present study we examined airway and lung parenchymal function 14 days after left pulmonary artery ligation. In rats as well as higher mammals, severe pulmonary ischemia results in bronchial vascular proliferation. Using labeled microspheres, we demonstrated an 18-fold increase in systemic blood flow to the ischemic left lung. Additionally, vascular remodeling extended to the tracheal venules, which showed an average 28% increase in venular diameter. Despite this increase in vascularity, airways resistance was not altered nor was methacholine responsiveness. Since these measurements include the entire lung, we suggest that the normal right lung, which represented 78% of the total lung, obscured the ability to detect a change. When functional indexes such as diffusing capacity, in situ lung volume, and vascular permeability of the left lung could be separated from right lung, significant changes were observed. Thus when comparing average left lung values of rats 14 days after left pulmonary artery ligation to left lungs of rats undergoing sham surgery, diffusing capacity of the left lung decreased by 72%, left lung volume decreased by 38%, and the vascular permeability to protein increased by 58%. No significant differences in inflammatory cell recruitment were observed, suggesting that acute ischemic inflammation had resolved. We conclude that despite the preservation of lung tissue, the proliferating bronchial neovasculature may contribute to a sustained decrement in pulmonary function.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Div. of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. wagnerem@jhmi.edu
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wagner
authors.forename: John
authors.initials: J
authors.lastname: Jenkins
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Perino
authors.forename: Adlah
authors.initials: A
authors.lastname: Sukkar
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D002908:Chronic Disease; D007511:Ischemia / Q000150:complications / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000503:physiopathology*; D011651:Pulmonary Artery / Q000503:physiopathology*; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley