title: Amiodarone improves cardiac sympathetic nerve function to hold norepinephrine in the heart, prevents left ventricular remodeling, and improves cardiac function in rat dilated cardiomyopathy.
abstract: 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.
  
  
  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-beta1 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.
authors.affiliation: First Department of Internal Medicine, Niigata University Graduate School of Medicine, Asahimachi 1-754, Niigata 951-8510, Japan. TachiHH@aol.com
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takahashi
authors.forename: Meilei
authors.initials: M
authors.lastname: Ma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kashimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Satoru
authors.initials: S
authors.lastname: Hirono
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okura
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics; D000638:Amiodarone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D006334:Heart Function Tests; D008297:Male; D009205:Myocarditis / Q000150:complications; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D019797:3-Iodobenzylguanidine; D000638:Amiodarone; D009638:Norepinephrine