ACUTE MYOCARDITIS CAUSES STRUCTURAL AND ELECTRICAL VENTRICULAR REMODELING -THE ROLE OFREDUCTION OF I_(TO)-RELATED MOLECULES IN EXPERIMENTAL AUTOIMMUNE MYOCARDITIS RAT-

摘要

BACKGROUND: We have reported that experimental autoimmune myocarditis (EAM) rats showed dramatic changes in ventricular action potential, but their mechanisms are unclear. To investigate the mechanism of cardiac remodeling in acute myocarditis and subsequent heart failure, physiological and molecular changes were evaluated. METHODS: On day 14, 21, 35 and 60 after immunization to Lewis rats, electrophysiological parameters and ionic changes were evaluated. Kv and L-Ca~(2+) channels, ion transporters and BNP expressions in the left ventricle were examined by real-time RT-PCR and Western blot analysis. Results: EAM showed acute myocarditis on day 14, day 21 and chronic DCM-like phase on day 60. HW/BW, LVEDP, and dP/dt were always higher in EAM than control. ERP and monophasic action potential duration (MAPD) were always longer in EAM, with a peak on day 21 which was parallel to PVC inducibility. mRNA levels of Kv4.2, Kvl.5, KChIP2, frequenin and SERCA, and the protein levels of Kv4.2 and Kvl.5 were reduced especially in acute phase. CONCLUSIONS: EAM showed structural and electrical remodeling in all phase, but most prominent change was documented in acute inflamatory phase. The reduction of Ito-related molecules and the prolongation of MAPD were considered to be a key mechanism of ventricular remodeling in EAM.