Original Article Elmer ress J Clin Med Res • 2012;4(3):190-196 Ultrastructural Changes in Rat’s Atrial Cardiomyocytes After Short Term Administration of Amiodarone and Possible Protective Role of Vitamin E Abdullah S. Shatoora, Mohamed Samir Ahmad Zakib, d, Refaat A. Eidc, Mohamed A. Sayed-Ahmadb Abstract Background: Amiodarone chlorhydrate is a diiodated benzofuran derivative used to treat a variety of cardiac rhythm abnormalities. The use of amiodarone is associated with ultrastructural changes affecting body tissues, but its effect on the ultrastructure of the heart has not yet been fully elucidated. Methods: The aim of this study is to test the adverse effects of amiodarone administration on cardiomyocytes and to study the pos- sible protective role of vitamin E co-administration. A total of 18 adult male albino rats were used in this study. The rats were divided randomly into three groups of 6 rats each as follows: group I was considered the control group and was given vegetable oil; group II received 54 mg/kg of oral amiodarone; and group III received a single dose of combined vitamin E (50 mg/kg) and amiodarone (54 mg/kg). After 2 weeks, the rats were sacrificed, and the atrial tissues were harvested and processed for electron microscopic study. Results: Administration of amiodarone alone modified the atrial architecture, which was demonstrated by the following: mitochon- drial enlargement and cristae lysis; marked heterogeneity of myo- fibril patterns with partial necrosis and disintegration of myofila- ments; and irregularities of the sarcomere and less concentration of atrionatriuretic factor (ANF) granules, which localised in closed proximity to the nucleus with disrupted chromatin contents. Con- Manuscript accepted for publication April 30, 2012 aInternal Medicine Department, Cardiology Section, Faculty of Medicine, King Khalid University, Saudi Arabia bAnatomy Department, Faculty of Medicine, King Khalid University, Saudi Arabia cPathology Department (Electron Microscopy Unit), Faculty of Medicine, King Khalid University, Saudi Arabia dCorresponding author: Mohamed Samir Ahmed Zaki, Histology and Cytology (Anatomy) Department, College of Medicine, King Khalid University (KKU), Abha 24121 Saudi Arabia. Email: mszaki1@hotmail.com doi:10.4021/jocmr909w comitant administration of vitamin E with amiodarone showed a considerable preservation of the atrial architecture. Conclusions: Oral administration of amiodarone in rats resulted in ultrastructural changes in atria, which can be attenuated by vitamin E co-administration. Keywords: Electron microscopy; Amiodarone; Cardiomyocytes Introduction It is well established that long-term oral administration of amiodarone is extremely effective in the management of most supraventricular and ventricular tachyarrhythmias [1, 2]. Amiodarone is categorised as a class III antiarrhythmic agent, as it prolongs the atrial and ventricular action poten- tial duration (APD) as well as the refractory period of car- diac muscle. These effects are potentiated when the drug is given for longer durations [3]. Compared to the action of most available antiarrhythmic agents, the oral administration of amiodarone has a nega- tive inotropic effect of lower significance and is less proar- rhythmic, making it advantageous for use in patients with impaired ventricular function [4, 5]. On the contrary, intra- venous administration of amiodarone in studies conducted on dogs resulted in considerable reduction of myocardial contractility [6, 7]. In spite of these advantages, adverse effects caused by amiodarone are frequent and can be serious and even lethal. Such reactions involve the liver [8], lungs [9-11], cornea [12], skin [13] and thyroid gland [14]. Evidence from in vitro and in vivo studies has attributed the pathogenesis of amiodarone toxicity to oxygen free radicals and oxidative stress [9, 10]. However, other studies do not support these findings. The effects of amiodarone on the mitochondrial oxidation of fatty acids in the liver of mice were determined [15-18]. Characteristic lamellar lysosomal inclusion bodies representing phospholipidosis were found in microscopi- cally studied liver specimens [17]. Vitamin E (α-tocopherol) is thought to protect tissues 190 Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press™ | www.jocmr.org This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited