Chronic airway obstruction and bronchiectasis in the rat after intratracheal bleomycin.

Abstract

Intratracheal instillation of bleomycin (BLM) has been used to generate rodent models of interstitial pulmonary fibrosis. In rats, we show that intratracheally instilled BLM evokes acute bronchopneumonia which persists and evolves into bronchiectasis associated with marked airflow dysfunction. Male F-344 rats, 11 weeks old, were treated once with BLM (4 or 5 units/kg body weight) and sacrificed at 2, 7, 14, 28, 56, and 154 d later for morphologic assessment. Static and dynamic pulmonary function tests were performed on the surviving rats 14 months and 2 years after treatment. The lungs from these rats were divided for histological and biochemical (elastin, hydroxyproline, DNA, protein) analyses. At both 14 months and 2 years, significantly depressed flow-volume curves and paradoxical increases in inflation pressure and residual volume were the predominant dysfunctions. Elastin and hydroxyproline levels, markedly elevated at 14 months, correlated with airflow dysfunction rather than loss of compliance. Light microscopy confirmed the presence of airway damage which comprised focal bronchiectasis and confluent peribronchial fibrosis.