Elucidating the relationship between arrhythmia and ischemic heterogeneity: an in silico study*

Dialysis causes blood flow defects in the heart that may augment electrophysiological heterogeneity in the form of increased number of ischemic zones in the human left ventricle. We computationally tested whether a larger number of ischemic zones aggravate arrhythmia using a 2D electrophysiological model of the human ventricle.A human ventricle cardiomyocyte model capable of simulating ischemic action potentials was adapted in this study. The cell model was incorporated into a spatial 2D model consisting of known number of ischemic zones. Inter-cellular gap junction coupling within ischemic zones was reduced to simulate slow conduction. Arrhythmia severity was assessed by inducing a re-entry, and quantifying the ensuing breakup and tissue pacing rates.Ischemia elevated the isolated cardiomyocyte’s resting potential and reduced its action potential duration. In the absence of ischemic zones, the propensity in the 2D model to induce multiple re-entrant waves was low. The inclusion of ischemic zones provided the substrate for initiation of re-entrant waves leading to fibrillation. Dominant frequency, which measured the highest rate of pacing in the tissue, increased drastically with the inclusion of multiple ischemic zones. Re-entrant wave tip maximum numbers increased from 1 tip (no ischemic zone) to 34 tips when a large number (20) of ischemic zones were included. Computational limiting factors of our platform were identified using software profiling.Clinical significance. Dialysis may promote deleterious arrhythmias by increasing tissue level action potential dispersion.