ACUTE PULMONARY INFLAMMATION IN HAMSTERS FOLLOWING INTRATRACHEAL ADMINISTRATION OF AMIODARONE

The use of the antiarrythmic drug amiodarone (AD) has been limited by the propensity of the drug to cause severe lung damage. AD has been shown to produce a transient pulmonary fibrosis in hamsters after intratracheal instillation. The goal of this study was to characterize the early inflammatory events associated with the administration of AD. Male Syrian hamsters that were instilled intratracheally with AD or saline vehicle underwent bronchoalveolar lavage (BAL). Total cells, macrophages, and eosinophils obtained by BAL were elevated by AD treatment at day 3. At both days 1 and 3 after instillation, AD-treated animals had significant elevations in neutrophil number. BAL fluid albumin was significantly elevated at day 1 in treated animals. Chemiluminescence (CL) performed on cells obtained by BAL showed an increase in CL of AD-treated samples compared to controls in phorbol myristate acetate (PMA) stimulated CL. PMA-induced increases in responsiveness were diminished by superoxide dismutase and catalase. These results indicate that oxidants such as superoxide and hydrogen peroxide may be involved in this inflammatory process. The results of this study show that intratracheal instillation of AD results in an inflammatory response that can be assessed by cellular, biochemical, and functional means.