Antiarrhythmic peptide AAP10 prevents ventricular arrhythmia in rabbit LQT2 model

Background and Objective Increased transmural dispersion of repolarization (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 E-4031 (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 AAP10 reduced endocardial action potential andTDR and prevented ventricular arrhythmia comparing with the control andAAP100nmol/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.