Differential susceptibilities of isolated hamster lung cell types to amiodarone toxicity

Treatment of cardiac dysrhythmias with the iodinated benzofuran derivative amiodarone (AM) is limited by pulmonary toxicity. The susceptibilities of d ifferent lung cell types of male Golden Syrian hamsters to AM-induced cytot oxicity were investigated in vitro. Bronchoalveolar lavage and protease dig estion to release cells, followed by centrifugal elutriation and density gr adient centrifugation, resulted in preparations enriched with alveolar macr ophages (98%), alveolar type II cells (75-85%), and nonciliated bronchiolar epithelial (Clara) cells (35-50%). Alveolar type II cell and Clara cell pr eparations demonstrated decreased viability (by 0.5% trypan blue dye exclus ion) when incubated with 50 mu M AM for 36 h, and all AM-treated cell prepa rations demonstrated decreased viability when incubated with 100 or 200 mu M AM. Based on a viability index ((viability of AM-treated cells divided by viability of controls) x 100%), the Clara cell fraction was significantly (p < 0.05) more susceptible than all of the other cell types to 50 mu M AM. However, AM cytotoxicity was greatest (p < 0.05) in alveolar macrophages f ollowing incubation with 100 or 200 mu M AM. There was no difference betwee n any of the enriched cell preparations in the amount of drug accumulated f ollowing 24 h of incubation with 50 mu M AM, whereas alveolar macrophages a ccumulated the most drug during incubation with 100 mu M AM. Thus, the most susceptible cell type was dependent on AM concentration. AM-induced cytoto xicity in specific cell types may initiate processes leading to inflammatio n and pulmonary fibrosis.