Introduction: Long QT Syndrome (LQTS) types 1 & 2 are ion channelopathies of the slow- (IKs) or rapid- (IKr) activating delayed rectifier K+ current that predispose individuals to cardiac arrhythmias, typified by polymorphic ventricular tachycardia known as Torsades de Pointes that can degenerate into ventricular fibrillation (VF). Mechanisms underlying LQTS arrhythmic-fatality are not fully known but may relate to reduced ventricular repolarising capacity. We aimed to use pharmacological models of LQTS 1&2 using HMR-1556 and E4031 respectively and examine the effects on the ventricle.Methods: Adult male Dunkin Hartley guinea pig hearts were used (410-490g) following a non-Schedule 1 killing method and perfused in constant flow Langendorff mode (37°C). Monophasic action potentials (MAP) were recorded at apex and base, measured at 90% decay (MAPD90). Effective refractory period (ERP) was measured using a single extrastimulus protocol with VF threshold (VFT) using rapid pacing. All measurements were taken at baseline (BL) and different doses of HMR (0.1,0.5,1µm,n=6) and E4031 (0.02,0.05,0.1µm,n=6). Values are mean±SEM, analysed with one-way ANOVA and Bonferroni post-hoc testResults: Both drugs reduced heart rate and increased ERP & VFT. The drugs increased MAPD90 at both apex and base in nearly equal amounts.Both drugs increased slopemax, with base/apex ratio increasing in a dose-dependent manner.Conclusion: HMR & E4031 mimic LQTS 1&2 by prolonging APD and increasing ERP by reducing repolarisation capacity of the ventricles. The Base/Apex slope ratio is increased by both drugs, suggesting that the drugs have a greater effect on restitution at the base than apex. This may be important in arrhythmogenesis in LQTS