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Transmural electrophysiological heterogeneities in action potential duration increase the upper limit of
T Maharaj1, B Rodriguez, R Blake
1Computing Laboratory, Oxford, UK. thum@comlab.ox.ac.uk
Insights
Transmural dispersion in action potential duration (APD) increases cardiac vulnerability to defibrillation shocks. This heightened vulnerability, driven by post-shock repolarization changes, may explain defibrillation failure during lethal arrhythmias.
Area of Science:
- Cardiac Electrophysiology
- Computational Cardiology
- Medical Device Engineering
Background:
- Transmural dispersion of action potential duration (APD) is linked to arrhythmia induction.
- The impact of APD dispersion on defibrillation shock efficacy remains unexplored.
Purpose of the Study:
- To investigate how transmural APD dispersion influences cardiac vulnerability to defibrillation shocks.
- To elucidate mechanisms underlying defibrillation failure.
Main Methods:
- Utilized a 3D finite element bidomain rabbit ventricular model.
- Incorporated transmural heterogeneities in ionic currents to simulate APD profiles.
- Analyzed virtual electrode polarization and post-shock electrical activity.
Main Results:
- Cardiac vulnerability to defibrillation shocks increased in models with heterogeneous APD compared to homogeneous models.
- The upper limit of vulnerability rose from 26.7 V/cm to 30.5 V/cm with transmural APD heterogeneities.
- Increased post-shock repolarization dispersion in the left ventricular wall was identified as a key factor.
Conclusions:
- Transmural APD dispersion elevates cardiac vulnerability to defibrillation shocks.
- This increased vulnerability is associated with greater post-shock repolarization dispersion, promoting re-entrant circuits.
- Findings offer insights into defibrillation failure mechanisms and potential therapeutic targets.
Abstract:
Transmural dispersion in action potential duration (APD) has been shown to contribute to arrhythmia induction in the heart. However, its role in termination of lethal arrhythmias by defibrillation shocks has never been examined. The goal of this study is to investigate how transmural dispersion in APD affects cardiac vulnerability to electric shocks, in an attempt to better understand the mechanisms behind defibrillation failure. This study used a three- dimensional, geometrically accurate finite element bidomain rabbit ventricular model. Transmural heterogeneities in ionic currents were incorporated based on experimental data to generate the transmural APD profile recorded in adult rabbits during pacing. Results show that the incorporation of transmural APD heterogeneities in the model causes an increase in the upper limit of vulnerability from 26.7 V/cm in the homogeneous APD ventricles to 30.5 V/cm in the ventricles with heterogeneous transmural APD profile. Examination of shock-end virtual electrode polarisation and postshock electrical activity reveals that the higher ULV in the heterogeneous model is caused by increased dispersion in postshock repolarisation within the LV wall, which increases the likelihood of the establishment of intramural re-entrant circuits.
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