Background Recent studies have identified that dyssynchronous ventricular activation can have detrimental effects including hypertrophy, dilatation and ultimately heart failure. The mechanisms are incompletely understood but appear to involve regional heterogeneities in ventricular workload. We investigated cellular remodelling in a model of dyssynchrony induced by right ventricular pacing, with regards to regional heterogeneity and how this relates to an existing model of heart failure. Methods Experiments were performed in female Welsh Mountain sheep, with isofluorane anaesthesia (1-4%) used for all surgical procedures. For the dyssynchrony model, transvenous pacemaker leads were implanted at the right ventricular apex and right atrial appendage. These were attached to a dual chamber pacemaker, programmed in VDD mode with a 40ms atrioventricular delay. For the heart failure model, the heart was paced at a rate of 210 bpm via a single lead implanted at the right ventricular apex. Pacing continued for 6-8 weeks in the heart failure model and 3 months in the dyssynchrony model. The animals were then euthanased with Pentobarbitone (200mg/kg IV) and the hearts excised. Ventricular myocytes were isolated by enzymatic digestion from the mid layer of the intraventricular septum (IVS) and left ventricular free wall (FW). After loading with Fura-2, these were studied at 37°C using the perforated patch current clamp technique. Action potentials were recorded at a stimulation frequency of 0.5Hz in normal Tyrode’s solution, and the time to 70% repolarisation (APD70) was measured. The magnitude of the calcium transient (Ca-Tran) was calculated, along with its exponential decay rate constant (Ca-RC). Statistical comparison was performed using 2 way ANOVA with significance accepted at p<0.05. Results Results are shown as mean ± standard deviation. APD70 was longer in the septum than the free wall and in both regions was shortened in heart failure. This was associated with a reduction in the magnitude and rate of decay of the calcium transient. Dyssynchrony was associated with a trend towards APD70 shortening, and no apparent effect on the calcium transient. Discussion These preliminary data suggest that this model of dyssynchrony may display similar action potential changes to the heart failure model. Further experiments will explore the underlying mechanisms, and whether dyssynchrony might be considered an intermediate stage in the remodelling seen in heart failure.