This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Filippatos, G. S. Articles by Utsumi, H. Search for Related Content PubMed PubMed Citation Articles by Filippatos, G. S. Articles by Utsumi, H. Related Collections Remodeling Apoptosis

(Circulation. 2000;102:e170.)
© 2000 American Heart Association, Inc.

Correspondence

Effects of Amiodarone on Heart Cells

Gerasimos S. Filippatos, MD

Second Department of Cardiology, Evangelismos General Hospital, 28 Doukissis Plakentias Street,, 115 23, Ambelokipi, Athens, Greece, geros@compulink.gr

Bruce D. Uhal, PhD

Cardiovascular Institute, Michael Reese Hospital, Chicago, Illinois

To the Editor:

We read with interest the article by Ide et al.¹ The authors showed that amiodarone protects cardiac myocytes against injury mediated by oxidative stress, and they conclude that this antioxidant action of amiodarone may contribute to the beneficial effects of this drug in patients with ischemic heart disease and heart failure.² Although this mechanism may well be active for the cardiac myocyte, the myocytes comprise a minor fraction of the total cell population of the heart, and the influence of amiodarone on other heart cells is largely unknown.

Cell death by apoptosis has been proposed as a possible mechanism for end-stage heart failure and for the deterioration of the heart, even in patients with moderate heart failure. It also has been proposed that the expression of tumor necrosis factor- (TNF-) increases oxidative stress and induces apoptosis in the heart. The recent demonstration that amiodarone decreases TNF- production by human blood mononuclear cells in response to³ lipopolysaccharide s consistent with that theory. However, the finding that amiodarone treatment is associated with an increase in TNF- levels in patients with ischemic cardiomyopathy⁴ does not support the existence of such a mechanism in vivo. Moreover, recent unpublished data from our laboratory show that amiodarone and its metabolite desethylamiodarone induce apoptosis in lung alveolar epithelial cells at doses equal to the therapeutic serum concentration of amiodarone. These agents are directly cytotoxic for lung fibroblasts and endothelial cells, albeit at somewhat higher concentrations, and on this basis, direct cytotoxicity has been . . . [Full Text of this Article]

Hiroyuki Tsutsui, MD, PhD

Tomomi Ide, , MD

Shintaro Kinugawa, MD

Akira Takeshita, MD, PhD

Department of Cardiovascular Medicine Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku,, Fukuoka, 812-8582, Japan, prehiro@cardiol.med.kyushu-u.ac.jp

Hideo Utsumi, PhD

Department of Biophysics, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan