Amiodarone-induced pulmonary fibrosis in Fischer 344 rats.

Amiodarone is a potent antiarrhythmic agent with a number of side-effects, the most serious being the development of pulmonary toxicity. The purpose of the study was to determine if a single intratracheal instillation of amiodarone would induce pulmonary fibrosis and associated functional changes in rats. Female Fischer 344 rats were given a single intratracheal instillation of 200 microliters containing 1.25 mg amiodarone (n = 9) while the control group received an equivalent volume of sterile water (n = 8). After 6 weeks, pulmonary function tests, lung hydroxyproline measurements and lung histology were performed. The amiodarone-treated animals showed a significant reduction in the coefficient of diffusion (kCO) and a significant increase in lung hydroxyproline levels as compared to the control group. The treated group had abnormal histology including areas of septal thickening with cellular infiltration of the interstitial and alveolar spaces, whereas the control group had normal histology. These observations suggest that the intratracheal instillation route of amiodarone treatment produces a fibrotic response in rats that can be measured physiologically, biochemically and histologically. This model may aid in the elucidation of the mechanism of amiodarone-induced pulmonary toxicity (AIPT)./ABS.