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(Circulation. 2005;111:894-899.)
© 2005 American Heart Association, Inc.

Heart Failure

Amiodarone Improves Cardiac Sympathetic Nerve Function to Hold Norepinephrine in the Heart, Prevents Left Ventricular Remodeling, and Improves Cardiac Function in Rat Dilated Cardiomyopathy

Hitoshi Tachikawa, MD; Makoto Kodama, MD; Kenichi Watanabe, MD, PhD; Toshihiro Takahashi, PhD; Meilei Ma, PhD; Takeshi Kashimura, MD; Masahiro Ito, MD; Satoru Hirono, MD; Yuji Okura, MD; Kiminori Kato, MD; Haruo Hanawa, MD; Yoshifusa Aizawa, MD

From the First Department of Internal Medicine (H.T., M.K., T.K., M.I., S.H., Y.O., K.K., H.H., Y.A.), Radioisotope Center (T.T.), Niigata University Graduate School of Medicine, and Department of Clinical Pharmacology, Niigata College of Pharmacy (K.W., M.M.), Niigata, Japan.

Correspondence to Hitoshi Tachikawa, MD, First Department of Internal Medicine, Niigata University Graduate School of Medicine, Asahimachi 1-754, Niigata 951-8510, Japan. E-mail TachiHH{at}aol.com

Received June 29, 2004; revision received September 24, 2004; accepted October 6, 2004.

Background— It is unclear how amiodarone therapy exerts its effects on left ventricular remodeling and cardiac sympathetic nerve function in chronic heart failure. We investigated long-term effects of amiodarone on rat dilated cardiomyopathy after healing of cardiac myosin–induced autoimmune myocarditis.

Methods and Results— Rats were treated with oral amiodarone or vehicle for 6 weeks. We determined cardiac function, left ventricular remodeling, and cardiac sympathetic nerve function with iodine-125–labeled metaiodobenzylguanidine ([I¹²⁵]MIBG). Amiodarone treatment improved left ventricular pressure, central venous pressure, and rate of isovolumetric contraction and decreased ventricular weight (P<0.005). Expression of cytokine mRNA was unchanged; expression of atrial natriuretic peptide, collagen III, and transforming growth factor-ß₁ mRNA was decreased in amiodarone-treated rats (P<0.05). Phenotype of myosin heavy chain was moved toward that of normal rats by amiodarone. Initial myocardial uptake of MIBG decreased by 67% (P<0.001) and washout rate accelerated by 221% in rats with chronic heart failure compared with normal rats. Whereas amiodarone decreased the initial uptake by 71% in normal rats, amiodarone decelerated the early washout and the late washout and improved the late myocardial distribution of MIBG in rats with chronic heart failure (257% compared with vehicle-treated rats with chronic heart failure; P<0.01). In proportion to MIBG distributions, cardiac tissue catecholamines were increased by amiodarone treatment.

Conclusions— Long-term amiodarone treatment prevented left ventricular remodeling and improved cardiac function in rat dilated cardiomyopathy. Long-term amiodarone treatment also restored cardiac sympathetic tone to hold norepinephrine in the heart.

Key Words: cardiomyopathy • antiarrhythmia agents • remodeling • nervous system, sympathetic

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