AMIODARONE-INDUCED PULMONARY FIBROSIS IN FISCHER-344 RATS

Amiodarone is a potent antiarrhythmic agent with a number of side-effe cts, the most serious being the development of pulmonary toxicity. The purpose of the study was to determine if a single intratracheal insti llation of amiodarone would induce pulmonary fibrosis and associated f unctional changes in rats. Female Fischer 344 rats were given a single intratracheal instillation of 200 mu l containing 1.25 mg amiodarone (n = 9) while the control group received an equivalent volume of steri le water (n = 8). After 6 weeks, pulmonary function tests, lung hydrox yproline measurements and lung histology were performed. The amiodaron e-treated animals showed a significant reduction in the coefficient of diffusion (kCO) and a significant increase in lung hydroxyproline lev els as compared to the control group. The treated group had abnormal h istology including areas of septal thickening with cellular infiltrati on of the interstitial and alveolar spaces, whereas the control group had normal histology. These observations suggest that the intratrachea l instillation route of amiodarone treatment produces a fibrotic respo nse in rats that can be measured physiologically, biochemically and hi stologically. This model may aid in the elucidation of the mechanism o f amiodarone-induced pulmonary toxicity (AIPT)./ABS .