Elucidating the Role of the His-Purkinje System During Long QT Mediated Arrhythmias

Long QT type 2 (LQT2) is a cardiac disorder caused by mutations in the hERG gene, which can lead to life-threatening arrhythmias. However, the exact involvement of the His-Purkinje System (HPS) in LQT2-mediated arrhythmias remains elusive. We utilized a computational model of the rabbit ventricles integrated with HPS to investigate the role of HPS in LQT2-mediated arrhythmia. We induced persistent reentry from an ectopic stimulus and isolated the HPS at different time points following the induction of reentry to determine its involvement in reentry dynamics. The earliest termination time for reentry coincided with the earliest time the HPS was isolated, indicating direct involvement of HPS in LQT2-mediated ventricular arrhythmia. Additionally, altering the HPS junctional parameters, such as coupling resistance or the number of myocytes at the Purkinje-Myocardial Junctions, affected reentry dynamics. Our multi-scale computer modeling outcomes offer important new understandings of probable arrhythmia mechanisms under LQT2 circumstances.