From the Purkinje fibres to the ventricle: One dimensional computer simulation for the healthy and failing heart

This study used one-dimensional computer simulation to investigate the influence of heart failure on action potential conduction through the left Purkinje fibres to the left ventricle. The study was based on a rabbit model of left ventricular heart failure caused by volume and pressure overload. To simulate the effect of heart failure, we began with models of the healthy rabbit Purkinje fibre action potential and healthy left ventricular (endocardial) action potential. In the absence of ionic current measurements from failing rabbit Purkinje fibres, we assumed that changes in ionic currents mirrored changes in ion channel expression (measured at the messenger RNA level): ionic conductances were adjusted based on changes in expression of the relevant ion channels. Ionic currents in the left ventricle were adjusted in the same way, but in addition, changes in ionic currents measured in the failing rabbit left ventricle by Ruijter et al. and Powizd et al. were used in simulations. The simulations predict a gradient in action potential duration from the Purkinje fibres to the ventricle and this gradient is exacerbated in heart failure. The predicted changes in the Purkinje fibre and left ventricular action potential were compared to actual changes measured using sharp microelectrodes.