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American Journal of Pathology, Vol 120, 344-350, Copyright © 1985 by American Society for Investigative Pathology

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Amiodarone-induced lung toxicity. In vitro evidence for the direct toxicity of the drug

WJ Martin and DM Howard

Amiodarone, a new antiarrhythmic agent, is associated with serious lung toxicity. This study indicates that in vitro amiodarone can directly induce bovine pulmonary artery endothelial cells to form cytoplasmic lamellar inclusions characteristic of the lung biopsy findings described in vivo. These morphologic changes occur as soon as 4 hours after incubation with the drug and with as little as 1 microgram/ml (within the therapeutic range). Amiodarone-induced endothelial cell injury, monitored by 51Cr release, occurs with as little as 10-20 micrograms/ml. The data suggest that amiodarone toxicity to the lung may be primarily related to its direct toxic effect on lung cells, and that the characteristic morphologic changes of cytoplasmic inclusions may represent an early sign of the drug's effect.

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