The fast conduction system, in particular the HisPurkinje-System (HPS), is a key element for coordinated electrical activation of the heart. However, it is often omitted in computational studies. We hypothesized that the inclusion of the HPS is necessary when investigating arrhythmia maintenance and termination in an ischemic heart. We used a computational model of regionally-ischemic human ventricles reconstructed from magnetic resonance imaging data, and combined this with a rule-based HPS that produced a realistic activation pattern. Simulations using a high-frequency pacing protocol showed that re-entrant waves through the ischemic region may retrogradely activate the HPS, leading to self-terminating ventricular tachycardia (VT). Simulations without the HPS maintained the ischemia-induced VT, highlighting the role of the HPS in arrhythmia termination. Optical mapping recordings from isolated Langendorf-perfused rabbit hearts during regional ischemia and ischemia-reperfusion are compatible with the conclusions from the in-silico model, showing patterns of re-entry and termination that may be generated from retrograde HPS conduction.