N-Acetylcysteine Suppresses the Progression of Ventricular Remodeling in Acute Myocarditis-Studies in an Experimental Autoimmune Myocarditis (EAM) Model-

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. Methods and Results: Six-week-old Lewis rats were immunized with porcine cardiac myosin. On Days 10 11 after the immunization, NAG (0, 1, 10, or 100 mg) 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 NAG-treatment in a dose-dependent manner (P < 0.05). In rats with 100 mg NAG, the myocarditis was almost totally negated although the mortality increased. In rats with 1 mg NAG, the suppression of myocarditis was not obvious, but APD prolongation and Kv4.2 reduction was attenuated (P < 0.05). Conclusions: The NAG 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. (Circ J 2011; 75: 662 671)