Document Detail


Rattus model utilizing selective pulmonary ischemia induces bronchiolitis obliterans organizing pneumonia.
MedLine Citation:
PMID:  23364425     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
John C Densmore; Paul M Jeziorczak; Anne V Clough; Kirkwood A Pritchard; Breana Cummens; Meetha Medhora; Arjun Rao; Elizabeth R Jacobs
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  39     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2013-07-30     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  271-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Caspase 3 / metabolism
Cryptogenic Organizing Pneumonia / etiology*,  metabolism,  pathology,  radionuclide imaging
Disease Models, Animal*
Ischemia / complications*,  metabolism,  pathology,  radionuclide imaging
Lung / blood supply*,  metabolism,  pathology,  radionuclide imaging
Male
Radiopharmaceuticals / diagnostic use
Rats
Rats, Sprague-Dawley
Severity of Illness Index
Sulfhydryl Compounds / diagnostic use
Technetium Tc 99m Aggregated Albumin / diagnostic use
Toll-Like Receptor 4 / metabolism
Grant Support
ID/Acronym/Agency:
8KL2TR000056/TR/NCATS NIH HHS; 8UL1TR000055/TR/NCATS NIH HHS; HL 102836/HL/NHLBI NIH HHS; HL 102996/HL/NHLBI NIH HHS; HL49294/HL/NHLBI NIH HHS; KL2 TR000056/TR/NCATS NIH HHS; L30 HL115450/HL/NHLBI NIH HHS; R01 HL049294/HL/NHLBI NIH HHS; R01 HL102836/HL/NHLBI NIH HHS; R01 HL116530/HL/NHLBI NIH HHS; R21 HL102996/HL/NHLBI NIH HHS; UL1 TR000055/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Radiopharmaceuticals; 0/Sulfhydryl Compounds; 0/Technetium Tc 99m Aggregated Albumin; 0/Tlr4 protein, rat; 0/Toll-Like Receptor 4; 0/technetium Tc99m-mercaptoacetyl albumin; EC 3.4.22.-/Caspase 3
Comments/Corrections

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