Myocardial ischemia could induce arrhythmias such as ventricular tachycardia and ventricular fibrillation, leading to sudden death and other serious consequences. This manuscript adopted the cardiac modeling and simulation method to study the activity pattern of myocardial ischemia-related ventricular tachycardia and the effect of increased extracellular potassium concentration on arrhythmia vulnerability. A whole ventricular electrophysiological model of endocardial ischemia caused by distal occlusion of left anterior descending coronary artery was established. The simulation results suggested that the relationship between the vulnerability of ventricular arrhythmias and extracellular potassium concentration was bell shaped with a peak in susceptibility at 12 mM. This result was caused by the effect of extracellular potassium concentration on the dispersion of repolarization and the effective refractory period of cardiomyocytes. The extension of the effective refractory period was due to the electrical remodeling of the ventricle. Specifically, it was because of the delayed recovery of the I_Na current. In addition, the regularity of endocardial/epicardial reentrant pattern during non-transmural ischemia was also analyzed. The endocardium formed micro-reentrant, while the epicardium established macro-reentrant rotating around the ischemic regions provided a new idea for the determination of clinical ablation targets.

(1) Background: The main factors and their interrelationships contributing to cardiac repolarization alternans (CRA) remain unclear. This study aimed to elucidate the calcium (Ca²⁺)-related mechanisms underlying myocardial ischemia (MI)-induced CRA. (2) Materials and Methods: CRA was induced using S1 stimuli for pacing in an in silico ventricular model with MI. The standard deviations of nine Ca²⁺-related subcellular parameters among heartbeats from 100 respective nodes with and without alternans were chosen as features, including the maximum systole and end-diastole and corresponding differences in the Ca²⁺ concentration in the intracellular region([Ca²⁺]_i) and junctional sarcoplasmic reticulum ([Ca²⁺]_jsr), as well as the maximum opening of the L-type Ca²⁺ current (I_CaL) voltage-dependent activation gate (d-gate), maximum closing of the inactivation gate (ff-gate), and the gated channel opening time (GCOT). Feature selection was applied to determine the importance of these features. (3) Results: The major parameters affecting CRA were the differences in [Ca²⁺]_i at end-diastole, followed by the extent of d-gate activation and GCOT among beats. (4) Conclusions: MI-induced CRA is primarily characterized by functional changes in Ca²⁺ re-uptake, leading to alternans of [Ca²⁺]_i and subsequent alternans of I_CaL-dependent properties. The combination of computational simulation and machine learning shows promise in researching the underlying mechanisms of cardiac electrophysiology.