Rat model of lung fibrosis: comparison of functional, biochemical, and histopathological changes 4 months after single irradiation of the right hemithorax

This study investigated changes in lung function, hydroxyproline (OH-pro) c ontent of lung tissue and histopathology in anesthetized, spontaneously bre athing rats after a single, selective irradiation of the right hemithorax w ith a single dose of 20 Gy. The objective of this animal model was to exami ne as to whether non-invasive lung function measurements (LFM) could be use d to analyze the magnitude of the irradiation-related pneumonitis and its l ong-term sequel occurring in the right lune in the presence of a normal lef t lung. Four months after irradiation. the OH-pro content in the irradiated right lung was determined and compared with the non-irradiated contralater al left lung, as well as lungs from non-irradiated sham controls. LFM revea led significantly depressed flow-volume curves and reduced quasistatic comp liance, 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 maldistributi on of ventilation shown by the single-breath N-2-wash-out lest. Single-brea th carbon monoxide diffusing capacity (Dlco) was significantly decreased. T he content of OH-pro. a marker of increased collagen: was significantly inc reased in the irradiated right lung but was indistinguishable from sham con trols in the non-irradiated left lung. Histopathological examinations provi ded evidence of both inflammatory and fibrotic lesions in the irradiated lo bes: including bronchiolo-alveolar hyperplasia. No changes were observed in the non-irradiated left lung. In summary, effects observed in the irradiat ed right lung were largely consistent with effects described in other anima l models of human interstitial pulmonary fibrosis. Non-invasive LFM were co nsidered to be particularly sensitive to study the overall extent of change s, however, the interpretation of findings appears to be complicated by the lobar heterogeneity of tissue- and how-related functional end points. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.