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

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Electrophysiology

Background:

• Dialysis can cause cardiac blood flow defects, potentially leading to electrophysiological heterogeneity.
• Increased ischemic zones in the left ventricle may augment arrhythmia risk.

Purpose of the Study:

• To computationally investigate if an increased number of ischemic zones aggravates cardiac arrhythmia.
• To model the impact of ischemia on human ventricular electrophysiology and re-entry dynamics.

Main Methods:

• Adapted a human ventricle cardiomyocyte model to simulate ischemic action potentials.
• Incorporated the cell model into a 2D spatial model with varying numbers of ischemic zones.
• Simulated slow conduction by reducing gap junction coupling within ischemic zones and assessed arrhythmia severity via re-entry induction and pacing rates.

Main Results:

• Ischemia elevated resting potential and reduced action potential duration in cardiomyocytes.
• The 2D model showed low propensity for re-entrant waves without ischemic zones.
• Inclusion of multiple ischemic zones initiated re-entrant waves, leading to fibrillation, and drastically increased dominant frequency.
• Re-entrant wave tips increased from 1 to 34 with 20 ischemic zones.

Conclusions:

• Multiple ischemic zones create a substrate for initiating re-entrant waves and promoting ventricular fibrillation.
• Dialysis-induced electrophysiological heterogeneity may promote deleterious arrhythmias.
• Computational models are valuable for understanding arrhythmia mechanisms in conditions like dialysis.