Amiodarone improves cardiac sympathetic nerve function to hold norepinephrine in the heart, prevents left ventricular remodeling, and improves cardiac function in rat dilated cardiomyopathy

作者：Tachikawa H^*; Kodama M; Watanabe K; Takahashi T; Ma ML; Kashimura T; Ito M; Hirono S; Okura Y; Kato K; Hanawa H; Aizawa Y

来源：Circulation, 2005, 111(7): 894-899.

DOI：10.1161/01.CIR.0000155610.49706.D2

• cardiomyopathy
• antiarrhythmia agents
• remodeling
• nervous system, sympathetic

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 ([I-125]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-β(1) 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.

• 出版日期2005-2-22