Background and Objective Increased transmural dispersion ofrepolarization (TDR) has been shown to contribute to initiation and maintenance of ventricular arrhythmia in long QT syndromes (LQTS).Intercellular uncoupling through gap junctions is an important mechanism for maintaining TDR in both intact and diseased heart.The present study was to test the hypothesis that improving gap junction communication reduces TDR and prevents ventricular arrhythmia in rabbit LQT2 model.Methods An arterially perfused rabbit left ventricular preparation and E4031 (0.5μmol/L) were used to establish a model of LQT2.Preparations were randomly assigned to control (n=10),AAP-100nmol/L(n=10),AAP-500nM(n=10) groups.Transmural ECG as well as action potentials from both endocardium and epicardium was simultaneously recorded.Results In LQT2 model,presence of 500nmol/L AAP 10 reduced endocardial action potential and TDR and prevented ventricular arrhythmia comparing with the control and AAP 100nmol/ L groups (P【0.05).Conclusions The presence of 500 nmol/L AAP10 reduces TDR and prevents ventricular arrhythmia in rabbit ventricular model of LQT2.This study suggests a possible role of GJs in TDR in rabbit LQT2 model and indicates a new clinical approach to the management of LQTS.
Background and Objective Increased transmural dispersion of repolarization (TDR) has been shown to contribute toinitiation and maintenance of ventricular arrhythmia in long QT syndromes(LQTS).Intercellular uncoupling through gap junctions isan important mechanism for maintaining TDR in both intact and diseased heart.The present study was to test the hypothesis thatimproving gap junction communication reduces TDR and prevents ventricular arrhythmia in rabbit LQT2 model.Methods Anarterially perfused rabbit left ventricular preparation and E-403 (0.5μmol/L)were used to establish a model of LQT2.Preparationswere randomly assigned to control(n=10),AAP-100nmol/L(n=10),AAP-500nM(n=10)groups.Transmural ECG as well as actionpotentials from both endocardium and epieardium was simultaneously recorded. Resuits In LQT2 model.presence of 500nmol/LAAP10 reduced endocardial action potential and TDR and prevented ventricular arrhythmia comparing with the control and AAP 100nmol/Lgroups(P<0.05).Conclusions The presence of 500 nmol/LAAP10 reduces TDR and prevents ventricular arrhythmia in rabbitventricular model of LOT2.This study suggests a possible role of GJs in TDR in rabbit LQT2 model and indicates a new clinicalapproach to the management of LQTS.