Rattus model utilizing selective pulmonary ischemia induces bronchiolitis obliterans organizing pneumonia.
Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of technetium Tc 99m macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase 3. Pulmonary artery blood flow to left lungs was less than 0.1% of the cardiac output, and bronchial artery circulation was ∼2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation, and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. In quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP.
Children's Research Institute, Milwaukee, WI, USA. jdensmore@chw.org
John C
JC
Densmore
Paul M
PM
Jeziorczak
Anne V
AV
Clough
Kirkwood A
KA
Pritchard
Breana
B
Cummens
Meetha
M
Medhora
Arjun
A
Rao
Elizabeth R
ER
Jacobs
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D018549:Cryptogenic Organizing Pneumonia / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007511:Ischemia / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008297:Male; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013438:Sulfhydryl Compounds; D013668:Technetium Tc 99m Aggregated Albumin; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D019275:Radiopharmaceuticals; D013438:Sulfhydryl Compounds; D013668:Technetium Tc 99m Aggregated Albumin; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C082426:technetium Tc99m-mercaptoacetyl albumin; D053148:Caspase 3