抄録
The Purkinje fiber network is one of the specialized excitation conduction systems that ensure coordinated contraction of the ventricles due to faster excitation conduction than other regions of the heart. A recent study identified a mutation in connexin 40 (Cx40), a gap junction isoform predominantly expressed in the His-Purkinje system, in patients with progressive cardiac conduction defect associated with lethal ventricular arrhythmias. This mutation disrupts the formation of gap junction channels in the His-Purkinje system, resulting in a decrease in gap junction conductance. However, the relationship between the reduced gap junction conductance and inducibility and sustainability of arrhythmias in the Purkinje fiber network is not clear. To elucidate the underlying mechanisms, we studied the relationship between cell-to-cell conduction property of the Purkinje fiber network and the initiation of ventricular arrhythmias using computer simulations. We used mathematical action potential models for rabbit Purkinje fiber and ventricular myocyte. Using these models, we constructed simplified anatomical models including action potential models to calculate excitation conduction from the His bundle to ventricular tissue via the Purkinje fiber network and Purkinje-ventricular junctions. Our His-Purkinje-ventricular network models was composed of approximately 13,000 cells, in which neighboring cells were connected by gap junction channels. To simulate mutation in connexin, gap junction conductance was reduced from 5,000 nS (physiological condition) to 10 nS. At lower gap junction conductances, reentrant beats occurred. When one of the reentrant circuits was disconnected, reentrant beats did not persist in some cases, as a consequence of altered excitation conduction dynamics. Our simulation results suggest that both Purkinje fiber network structure and gap junction conductance are important factors for generating arrhythmias in the Purkinje fiber network. In addition, ablation applied to the reentrant circuit in the His-Purkinje-ventricular network is a potential preventive treatment for arrhythmias generated from the Purkinje fiber network.
