Bleomycin-induced Fibrosis In Swine: A Correlative Radiology And Pathology Study.

Bleomycin is an important and effective antitumor agent. However, use of the drug is related to the development of pulmonary fibrosis. The development of bleomycin-induced lung toxicity has been extensively examined in animals. It was initially observed in dogs but most of the subsequent works has been on rodents. These small experimental animals are not suitable for radiologic-pathologic evaluation. So we established a dog model for bleomycin-induced fibrosis and studied the CT and MRl characteristics of experimentally induced interstitial pulmonary fibrosis with precise radiologic-pathologic correlation. The significance of the bronchiole alveolar lavage was also appreciated. Materials and methods:35 healthy adult mongrel dogs weighing 14.3 ±4.0 Kg (mean±SD) were randomized into three groups. The models of bleomycin-induced pulmonary fibrosis were established by 3 methods: ①intrabroncheal instilling of a single dose of bleomycin A5 (n=6); ②intrabroncheal aerosolizing ventilation of a single dose (n=24); (3) mixed pulmonary perfusion and intrabroncheal aerosolizing ventilation(n=5). Another five dogs served as control. In control group, the bleomycin was replaced by physiologic saline solution. The baseline and sequential HRCT and MRl examinations were acquired on days 0,3,7,14 and months 1,2,4,5,6,8 after treatment. The animals were sacrificed at the predetermined date and the lungs were removed and fixed with the method described by Heitzman. The electron microscopy examination was also performed on five dogs in group 2. RESULTS:All animals tolerated the modeling procedures well. Both HRCT and patho-histological examination revealed typical fibrosis formation, but there were significant individual differences. HRCT demonstrated different changes produced by different methods of drug delivery and good correlation between...