Ultrastructural Study of Amiodarone-Associated Lung Injury

Kim, Eun Yung; Lee, Sang Han; Sohn, Yoon Kyung; Sohn, Tae Joong

Abstract

Amiodarone, an antiarrhythmic drug, may exert pulmonary toxicity in some patients but the pathogenesis is not clear. This study was carried out to investigate the pathogenetic mechanism of pulmonary injury induced by amiodarone at dose of 100 mg/kg/day given to rats by intraperitoneal injection for 3 weeks. And the preventive effects of concomitantly injected steroid (10 mg/kg/day) on amiodarone induced pulmonary injury was also studied using bronchoalveolar lavage, light microscopy and transmission electron microscopy. The results obtained were summarized as follows: Mild lymphocytosis of bronchoalveolar lavage fluid was found in all experimental groups. Intracytoplasmic lamellar body formation was found in all types of pulmonary cells and type II pneumocytes revealed the earliest abnormal lamellar body formation. The capillary endothelial cells showed cellular swelling and detachment from underlying basement membrane at early phase of experiment and the edema of alveolar wall and interstitium were noted. Interstitial fibrosis and proliferation of type II pneumocytes were noted at late phase. The lungs of steroid injected groups revealed accumulation of lamellar bodies in all types of pulmonary cells but interstitial fibrosis was not occurred. These findings support the concept that amiodarone is responsible for a drug-induced phospholipidosis and directly toxic to pulmonary endothelial and epithelial cells. And steroid may regress the progression of amiodarone induced pulmonary injury.