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 sh own to produce a transient pulmonary fibrosis in hamsters after intrat racheal instillation. The goal of this study was to characterize the e arly inflammatory events associated with the administration of AD. Mal e Syrian hamsters that were instilled intratracheally with AD or salin e vehicle underwent bronchoalveolar lavage (BAL). Total cells, macroph ages, and eosinophils obtained by BAL were elevated by AD treatment at day 3. At both days 1 and 3 after instillation, AD-treated animals ha d significant elevations in neutrophil number. BAL fluid albumin was s ignificantly 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 diminish ed by superoxide dismutase and catalase. These results indicate that o xidants such as superoxide and hydrogen peroxide may be involved in th is inflammatory process. The results of this study show that intratrac heal instillation of AD results in an inflammatory response that can b e assessed by cellular, biochemical, and functional means.