Introduction: Congenital long QT syndrome 1 (LQTS1) arises from a reduced activity of the slow activating delayed rectifier potassium channel (IKs). Ventricular arrhythmias occur along with increases in sympathetic tone, which can cause sudden cardiac death (SCD). Mechanisms underlying SCD are not understood but may involve changes in ventricular electrophysiology including electrical restitution (RT) – the relationship between action potential duration and diastolic interval. The aim was to develop the innervated heart preparation in the guinea pig and examine the effects of sympathetic nerve stimulation (SNS) on effective refractory period (ERP) and inducibility of ventricular fibrillation (VF) in a pharmacological model of LQTS1. Methods: After anaesthesia (Urethane, 2.5g/kg) was achieved, the decentralised isolated Langendorff perfused innervated heart preparation from adult male guinea pigs (n=6, 450-550g) was prepared. Animals were killed with pentobarbitone (160mg/kg, iv) and the preparation was perfused via the aorta in constant flow. The innervated heart preparation from adult male guinea pigs (n=6, 450-550g) were used. ERP was measured using an extrastimulus protocol whilst the inducibility of VF was assessed with ventricular fibrillation threshold (VFT) during burst pacing. The parameters were measured at baseline (BL) and with SNS (3Hz, 1V) during control and in the presence of the IKs blocker HMR1556 to mimic LQTS1. Data are mean±SEM, analysed using paired Student’s T-Test. Results: During control, SNS significantly reduced ERP and VFT (Table, P<0.05 * vs. BL, ~ vs. Control). In the presence of HMR1556, the effects of SNS on ERP and VFT were augmented whilst the effect on RT was abolished. Conclusion: SNS increases susceptibility to VF which appears to be augmented in this pharmacological LQTS1 model and maybe related to changes in ERP.