Long QT Syndrome (LQTS) 1&2 are life-threatening conditions that arise from dysfunction of slow (IKs) and rapid (IKr) components of the delayed rectifier K+ current respectively. The consequential impairment of ventricular repolarisation predisposes individuals to ventricular fibrillation (VF). It is known that sympathetic surges often precede VF in LQTS, but mechanisms of initiation are not understood. We aim to use pharmacological models of LQTS 1&2 in combination with the β-adrenoreceptor (β-AR) agonist isoproterenol (ISO), to mimic sympathetic stimulation to examine effects on the ventricular electrophysiology. Adult male Dunkin Hartley guinea pig hearts (400-600g, n=12) were used in constant flow Langendorff mode following a licenced non-Schedule 1 culling procedure. Ventricular Monophasic Action Potentials (MAPs) were recorded at apical and basal sites and measured at 90% decay (MAPD90). Effective refractory period (ERP) / action potential duration restitution (RT) and ventricular fibrillation threshold (VFT) were measured using an extrastimulus and burst pacing protocol respectively. All tests were performed at control, ISO (10nM), LQTS drug and ISO + LQTS drug. HMR-1556 (HMR; 0.5μM, n=6) and E4031 (0.05μM, n=6) were used to replicate LQTS 1 & 2 respectively. Data is shown as mean±SEM and analysed using ANOVA, p<0.05 was considered significant. Both HMR and E4031 have a bradycardic effect, but the application of ISO to LQTS models increased HR significantly compared to control. β-AR stimulation had different effects on the LQTS models: in LQT1, the presence of ISO caused a flattening of the RT curve, but in LQT2 the RT curve gradient was significantly steeper than in control conditions. Both ERP and VFT were increased during HMR and E4031 perfusion, but decreased when ISO was applied to both models. The preliminary data suggest that both LQTS 1&2 are associated with an increase in VF susceptibility when sympathetic activity is enhanced, in terms of ERP and VFT. However, there is a dichotomy in the effect on RT slope gradient between the two models, where β-AR stimulation flattens the RT slope in LQTS 1 model but steepens the RT slope in LQTS 2 model; this implies that there may be different mechanisms involved in arrhythmogenesis.