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Rattus model utilizing selective pulmonary ischemia induces bronchiolitis obliterans organizing pneumonia. Shock 2013 Mar;39(3):271-7

Date

02/01/2013

Pubmed ID

23364425

Pubmed Central ID

PMC3578046

DOI

10.1097/SHK.0b013e318281a58c

Scopus ID

2-s2.0-84874256858   7 Citations

Abstract

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.

Author List

Densmore JC, Jeziorczak PM, Clough AV, Pritchard KA Jr, Cummens B, Medhora M, Rao A, Jacobs ER

Authors

Anne Clough PhD Professor in the Mathematics, Statistics, and Computer Science department at Marquette University
John C. Densmore MD Professor in the Surgery department at Medical College of Wisconsin
Elizabeth R. Jacobs MD Associate Dean, Professor in the Medicine department at Medical College of Wisconsin
Meetha M. Medhora PhD Professor in the Radiation Oncology department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Caspase 3
Cryptogenic Organizing Pneumonia
Disease Models, Animal
Ischemia
Lung
Male
Radionuclide Imaging
Radiopharmaceuticals
Rats
Rats, Sprague-Dawley
Severity of Illness Index
Sulfhydryl Compounds
Technetium Tc 99m Aggregated Albumin
Toll-Like Receptor 4
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a