Computer simulation of Purkinje fibres from a rabbit model of congestive heart failure

This study used computer simulation to investigate the influence of heart failure (HF) on the Purkinje fibre. The study was based on a rabbit model of HF caused by volume and pressure overload. In the left ventricular free running Purkinje fibres, the expression level of the key cardiac ion channels was measured at the mRNA (messenger RNA) level using qPCR (quantitative polymerase chain reaction). Major changes were observed. To simulate the effect of these changes, we began with a model of the healthy rabbit Purkinje fibre 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: ionic conductances were adjusted based on changes in expression of the relevant ion channels. In the simulations, if all changes observed were incorporated, the Purkinje fibre is predicted to become inexcitable. Such an outcome would result in left bundle branch block (as observed in HF patients). The simulations predict that HF-dependent changes in I
_NaL
, I
_to
, I
_Kr
and I
_K1
and will have the most influence on the Purkinje fibre action potential. The predicted changes in the Purkinje fibre action potential were compared to actual changes measured using sharp microelectrodes.