The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

Abstract

Transmural electrophysiological heterogeneities have been shown to contribute to arrhythmia induction in the heart; however, their role in defibrillation failure has never been examined. The goal of this study is to investigate how transmural heterogeneities in ionic currents and gap-junctional coupling contribute to arrhythmia generation following defibrillation strength shocks. This study used a 3D anatomically realistic bidomain model of the rabbit ventricles. Transmural heterogeneity in ionic currents and reduced sub-epicardial intercellular coupling were incorporated based on experimental data. The ventricles were paced apically, and truncated-exponential monophasic shocks of varying strength and timing were applied via large external electrodes. Simulations demonstrate that inclusion of transmural heterogeneity in ionic currents results in an increase in vulnerability to shocks, reflected in the increased upper limit of vulnerability, ULV, and the enlarged vulnerable window, VW. These changes in vulnerability stem from increased post-shock dispersion in repolarisation as it increases the likelihood of establishment of re-entrant circuits. In contrast, reduced sub-epicardial coupling results in decrease in both ULV and VW. This decrease is caused by altered virtual electrode polarisation around the region of sub-epicardal uncoupling, and specifically, by the increase in (1) the amount of positively polarised myocardium at shock-end and (2) the spatial extent of post-shock wavefronts.

Fig. 1

(A) Anterior epicardial and (B) basal transmural views of the rabbit ventricular model with the shock electrodes at the boundaries of the perfusing chamber, the pacing electrode at the apex (E1), and the ECG electrode (E2). Pre-shock epicardial transmembrane potential distribution corresponds to a coupling interval of 140 ms in the heterogeneous ventricles.

Fig. 2

Time course of an action potential computed using (A) a single cell model with membrane kinetics as used in the homogeneous model and (B) models of epicardial (solid), midmyocardial (dotted) and endocardial (dashed) single cells as implemented in the heterogeneous models. Basic cycle length is 250 ms.

Fig. 3

Electrical activity following the application of the 7th apical pacing stimulus to the homogeneous ventricles (panel A), the heterogeneous ventricles (panel B), and the heterogeneous ventricles with sub-epicardial uncoupling (panel C), I). Activation maps; (II) repolarisation maps; (III) APD maps (left) and time course of the action potentials (right) from an LV node in the homogeneous model (panel A), and from LV nodes located in the mid-section of the epicardial (blue), the midmyocardial (green), and the endocardial (red) layers of the heterogeneous model (panel B) and the heterogeneous model with sub-epicardial uncoupling (panel C) IV) time course of the pseudo-ECGs recorded at the E2 electrode as shown in Fig. 1. RT_min and RT_max indicate the earliest and latest local repolarisation times (RT) within the ventricles.

Fig. 4

Vulnerability areas for (A) the homogeneous model, (B) the heterogeneous model and (C) the heterogeneous model with sub-epicardial uncoupling. Dots represent episodes of shock delivery. Dark and light grey areas encompass episodes of sustained and unsustained re-entry, respectively.

Fig. 5

Transmembrane potential distributions and distributions of filaments at shock-end (0 ms panels) and at 20, 50 and 100 ms following a shock applied at CI = 140 ms of strength 11.43 V/cm in the homogeneous (panels A and D) and in the heterogeneous (panels B and E) model, and of strength 7.62 V/cm in the heterogeneous model with sub-epicardial uncoupling (panels C and F). Panels A–C show anterior epicardial and transmural views. In panels D–F, the epicardial surface has been rendered semi-transparent to allow visualisation, in pink, of scroll-wave filaments. Colour scale is saturated, i.e. transmembrane potential above 20 mV and below –90 mV appear red and blue, respectively. Arrows indicate the direction of wave propagation.

Fig. 6

Percentage of myocardial nodes that are of transmembrane potential above +20 mV (black bars) and below –90 mV (grey bars) at the end of a 11.43 V/cm shock applied at CIs in the range of 100–200 ms in the homogeneous model (panel A), the heterogeneous model (panel B), and the heterogeneous model with sub-epicardial uncoupling (panel C).

Fig. 7

Spatial extent of post-shock wavefronts (calculated as a percentage of all myocardial nodes activated during the first two milliseconds following shock-end) as a function of coupling interval at the end of a 11.43-V/cm shock in all three models.

Fig. 8

Transmembrane potential and filament distributions at shock-end (0 ms panels) and at 20, 50 and 100 ms following a 30.5-V/cm shock applied at a CI of 140 ms to the homogeneous ventricles (panels A and D), to the heterogeneous ventricles (panels B and E), and to the heterogeneous ventricles with sub-epicardial uncoupling (panels C and F). Panels A–C show anterior epicardial and transmural views. In panels D–F, the epicardial surface has been rendered semi-transparent to allow visualisation, in pink, of scroll-wave filaments. Colour scale is saturated, i.e. transmembrane potential above 20 mV and below –90 mV appear red and blue, respectively. Arrows indicate the direction of propagation, and circles denote the presence or lack thereof of a local wavefront on the epicardial surface at 50 ms post-shock.