Document Detail

Rat model of lung fibrosis: comparison of functional, biochemical, and histopathological changes 4 months after single irradiation of the right hemithorax.
MedLine Citation:
PMID:  11297804     Owner:  NLM     Status:  MEDLINE    
This study investigated changes in lung function, hydroxyproline (OH-pro) content of lung tissue and histopathology in anesthetized, spontaneously breathing rats after a single, selective irradiation of the right hemithorax with a single dose of 20 Gy. The objective of this animal model was to examine as to whether non-invasive lung function measurements (LFM) could be used to analyze the magnitude of the irradiation-related pneumonitis and its long-term sequel occurring in the right lung in the presence of a normal left lung. Four months after irradiation, the OH-pro content in the irradiated right lung was determined and compared with the non-irradiated contralateral left lung, as well as lungs from non-irradiated sham controls. LFM revealed significantly depressed flow-volume curves and reduced quasistatic compliance, suggesting a marked diminution of elastic recoil of the lung. Total lung capacity (TLC) was significantly decreased, while the residual volume (RV) and functional residual capacity (FRC) remained almost unchanged. One of the most predominant dysfunction of the lung was a severe maldistribution of ventilation shown by the single-breath N(2)-wash-out test. Single-breath carbon monoxide diffusing capacity (Dlco) was significantly decreased. The content of OH-pro, a marker of increased collagen, was significantly increased in the irradiated right lung but was indistinguishable from sham controls in the non-irradiated left lung. Histopathological examinations provided evidence of both inflammatory and fibrotic lesions in the irradiated lobes, including bronchiolo-alveolar hyperplasia. No changes were observed in the non-irradiated left lung. In summary, effects observed in the irradiated right lung were largely consistent with effects described in other animal models of human interstitial pulmonary fibrosis. Non-invasive LFM were considered to be particularly sensitive to study the overall extent of changes, however, the interpretation of findings appears to be complicated by the lobar heterogeneity of tissue- and flow-related functional end points.
J Pauluhn; M Baumann; C Hirth-Dietrich; M Rosenbruch
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Toxicology     Volume:  161     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-04-12     Completed Date:  2001-05-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  153-63     Citation Subset:  IM    
Institute of Toxicology, Bayer AG, Building no. 514, 42096, Wuppertal, Germany.
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MeSH Terms
Airway Resistance
Disease Models, Animal
Hydroxyproline / metabolism
Lung / metabolism,  pathology,  physiopathology,  radiation effects*
Lung Volume Measurements
Peak Expiratory Flow Rate
Pulmonary Fibrosis / metabolism,  pathology,  physiopathology*
Radiation Pneumonitis / metabolism,  pathology,  physiopathology*
Rats, Inbred F344
Tidal Volume
Reg. No./Substance:

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