Snyder V L, Bandyopadhyay S, Collins J, Gross S A, Somani P, Didio L J
Department of Anatomy, Medical College of Ohio, Toledo.
J Submicrosc Cytol Pathol. 1990 Jan;22(1):71-8.
Amiodarone, an antiarrhythmic agent, has proven to be unique in its capability to control arrhythmias unresponsive to conventional drugs. However, its association with many undesirable side effects after chronic usage has become just as clear. Chronic clinical toxicity with amiodarone is associated with intracellular lamellar or myelinoid inclusion bodies (onionoid bodies or corpora cepiformia) in various organs (i.e. skin, cornea, lung, liver, and lymph nodes). Previous study has demonstrated formation of these inclusion bodies in canine myocardium following multiple doses of amiodarone. The present study was designed to develop a more convenient animal model, and to measure the concentration of amiodarone, as well as desethylamiodarone (its major metabolite) in this rodent model. The direct role of desethylamiodarone in formation of lamellar inclusion bodies in rat myocardium was also investigated. Amiodarone (50 mg/kg) or desethylamiodarone (25 mg/kg) was injected intraperitoneally daily for a period of 14 days. Myocardial sections revealed the presence of lamellar inclusion bodies, round or oval in appearance, in the form of laminated or concentrically arranged membranes after either amiodarone or desethylamiodarone treatment. This is the first reference to the induction of these myelinoid inclusion bodies with desethylamiodarone. Myocardial tissue concentrations of amiodarone and desethylamiodarone exceeding plasma concentrations were found in the present study and indicate the capability of these compounds to easily distribute and accumulate in the myocardium.
胺碘酮是一种抗心律失常药物，已被证明在控制对传统药物无反应的心律失常方面具有独特能力。然而，长期使用后它与许多不良副作用的关联也已十分明确。胺碘酮的慢性临床毒性与各器官（如皮肤、角膜、肺、肝脏和淋巴结）内的细胞内板层状或髓鞘样包涵体（洋葱样小体或脑形小体）有关。先前的研究已证明多次给予胺碘酮后犬心肌中会形成这些包涵体。本研究旨在建立一种更便捷的动物模型，并测定该啮齿动物模型中胺碘酮及其主要代谢产物去乙基胺碘酮的浓度。同时还研究了去乙基胺碘酮在大鼠心肌中板层状包涵体形成过程中的直接作用。每天腹腔注射胺碘酮（50毫克/千克）或去乙基胺碘酮（25毫克/千克），持续14天。心肌切片显示，经胺碘酮或去乙基胺碘酮治疗后，出现了外观呈圆形或椭圆形的板层状包涵体，其形态为层状或同心排列的膜。这是首次提及去乙基胺碘酮可诱导这些髓鞘样包涵体。本研究发现心肌组织中胺碘酮和去乙基胺碘酮的浓度超过血浆浓度，这表明这些化合物能够轻易地在心肌中分布和蓄积。
