Triggers of ventricular tachyarrhythmias and therapeutic effects of nicorandil in canine models of LQT2 and LQT3 syndromes.

OBJECTIVES We sought to identify the triggers of ventricular tachyarrhythmia (VTA) in experimental models of long QT type 2 (LQT2) and long QT type 3 (LQT3) syndromes. BACKGROUND Most adverse cardiac events occurring in the long QT type 1 syndrome are related to sympathetic nerve activity. In contrast, various factors may trigger VTA in patients with LQT2 and LQT3. METHODS The mode of onset of VTA and therapeutic effects of the potassium-adenosine triphosphate channel opener nicorandil were compared in canine models of LQT2 and LQT3, using three induction protocols: 1) bradycardia produced by atrioventricular block (BRADY); 2) programmed ventricular stimulation; and 3) electrical stimulation of the left stellate ganglion (left stellate stimulation [LSS]). Transmural unipolar electrograms were recorded, and the activation-recovery interval (ARI) was measured. RESULTS Ventricular tachyarrhythmias developed during BRADY in all six experiments in the LQT3 model, but in none of the six experiments in LQT2. Programmed ventricular stimulation induced VTA in two experiments of the LQT2 model, but in none of the LQT3 experiments. Stimulation of the left stellate ganglion induced VTA in three experiments in LQT2 and in two experiments in LQT3. Nicorandil caused greater shortening of ARI and greater attenuation of transmural ARI dispersion in the LQT2 model than in the LQT3 model. After treatment with nicorandil, a single VTA was induced in the LQT2 model by LSS, whereas in the LQT3 model, VTA remained inducible by BRADY in four experiments and LSS in one experiment. CONCLUSIONS An abrupt increase in sympathetic activity appeared arrhythmogenic in both models. Nicorandil attenuated the heterogeneity of ventricular repolarization and suppressed the induction of VTA in the LQT2 model, but had a limited therapeutic effect in the LQT3 model.