title: N-acetylcysteine suppresses the progression of ventricular remodeling in acute myocarditis: studies in an experimental autoimmune myocarditis (EAM) model.
abstract: BACKGROUND
  Electrical and structural remodeling, characterized by prolonged action potential duration (APD), Kv4.2 downregulation and cellular infiltration were studied in rat experimental autoimmune myocarditis (EAM). Because the reactive oxygen species (ROS) has been speculated to play a role in the promotion of such remodeling, the effect of N-acetylcysteine (NAC) on the progression of ventricular remodeling was evaluated.
  
  
  RESULTS
  Six-week-old Lewis rats were immunized with porcine cardiac myosin. On Days 10-11 after the immunization, NAC (0, 1, 10, or 100mg) was injected intraperitoneally to EAM and control rats. On Day 14, the electrophysiological parameters were evaluated and the expression levels of the mRNA were examined by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR).The EAM rats exhibited a typical acute myocarditis with prolonged APD and reduced Kv4.2 expression as previously reported. The myocarditis and electrical changes were significantly suppressed by NAC-treatment in a dose-dependent manner (P<0.05). In rats with 100mg NAC, the myocarditis was almost totally negated although the mortality increased. In rats with 1mg NAC, the suppression of myocarditis was not obvious, but APD prolongation and Kv4.2 reduction was attenuated (P<0.05).
  
  
  CONCLUSIONS
  The NAC treatment suppressed ventricular remodeling in the EAM rats. This may indicate the role of oxidative stress in causing remodeling and myocarditis itself in the acute phase of myocarditis.
authors.affiliation: Department of Cardio-Angiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Japan. shniwano@med.kitasato-u.ac.jp
authors.forename: Shinichi
authors.initials: S
authors.lastname: Niwano
authors.forename: Hiroe
authors.initials: H
authors.lastname: Niwano
authors.forename: Sae
authors.initials: S
authors.lastname: Sasaki
authors.forename: Hidehira
authors.initials: H
authors.lastname: Fukaya
authors.forename: Masaru
authors.initials: M
authors.lastname: Yuge
authors.forename: Ryuta
authors.initials: R
authors.lastname: Imaki
authors.forename: Yoji
authors.initials: Y
authors.lastname: Machida
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D009205:Myocarditis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000111:Acetylcysteine