Effects of mechano-electric feedback on scroll wave stability in human ventricular fibrillation

Abstract

Recruitment of stretch-activated channels, one of the mechanisms of mechano-electric feedback, has been shown to influence the stability of scroll waves, the waves that underlie reentrant arrhythmias. However, a comprehensive study to examine the effects of recruitment of stretch-activated channels with different reversal potentials and conductances on scroll wave stability has not been undertaken; the mechanisms by which stretch-activated channel opening alters scroll wave stability are also not well understood. The goals of this study were to test the hypothesis that recruitment of stretch-activated channels affects scroll wave stability differently depending on stretch-activated channel reversal potential and channel conductance, and to uncover the relevant mechanisms underlying the observed behaviors. We developed a strongly-coupled model of human ventricular electromechanics that incorporated human ventricular geometry and fiber and sheet orientation reconstructed from MR and diffusion tensor MR images. Since a wide variety of reversal potentials and channel conductances have been reported for stretch-activated channels, two reversal potentials, -60 mV and -10 mV, and a range of channel conductances (0 to 0.07 mS/µF) were implemented. Opening of stretch-activated channels with a reversal potential of -60 mV diminished scroll wave breakup for all values of conductances by flattening heterogeneously the action potential duration restitution curve. Opening of stretch-activated channels with a reversal potential of -10 mV inhibited partially scroll wave breakup at low conductance values (from 0.02 to 0.04 mS/µF) by flattening heterogeneously the conduction velocity restitution relation. For large conductance values (>0.05 mS/µF), recruitment of stretch-activated channels with a reversal potential of -10 mV did not reduce the likelihood of scroll wave breakup because Na channel inactivation in regions of large stretch led to conduction block, which counteracted the increased scroll wave stability due to an overall flatter conduction velocity restitution.

Figure 1. MRI-based electromechanical model of the human ventricles.

(A): The mechanical mesh, fiber orientation and sheet structure of the human ventricular model. (B): The schematic diagram of the electromechanical model.

Figure 2. VF in the electromechanical model without SAC representation.

(A): Epicardial transmembrane potential distribution maps on the posterior wall from the simulation without SAC representation. Pink dots indicate the locations of the phase singularities. (B): Posterior semi-transparent view of the ventricles shows the filament distribution (blue). (C): Pseudo-ECG.

Figure 3. Recruitment of SAC with V_SAC of −60 mV flattens the single-cell APD restitution curve.

Changes in the single-cell APD restitution curves due to SAC opening for different values of λ_f. (A): g_SAC = 0.03 mS/µF, (B): g_SAC = 0.05 mS/µF and (C): g_SAC = 0.07 mS/µF.

Figure 4. Recruitment of SAC with V_SAC of −60 mV diminishes scroll wave breakup.

(A): Snapshot of the heterogeneous λ_f distribution at 2.3 s after arrhythmia induction for the ventricular model with V_SAC of −60 mV; g_SAC = 0.07 mS/µF. In plotting the λ_f distribution, the range 1.0 to 1.2 was chosen for visual purposes, as 90% of the data points fell within this range. (B): Maximum APD restitution slope distribution for the same model and time instant as in (A). In plotting of maximum APD restitution slopes, the range 0.2 to 1.5 was chosen for visual purposes, as 97% of the data points fell within this range. (C): Epicardial transmembrane potential distribution map on the anterior wall for V_SAC of −60 mV and g_SAC of 0.07 mS/µF when λ_f was assumed constant and equal to 1.2. Pink dot indicates the location of the phase singularity.

Figure 5. Recruitment of SAC with V_SAC of −10 mV diminishes scroll wave breakup at low g_SAC.

Changes in the CV restitution curves due to SAC opening for different values of λ_f. (A): g_SAC = 0.02 mS/µF, (B): g_SAC = 0.04 mS/µF and (C): g_SAC = 0.07 mS/µF. (D): Epicardial transmembrane potential distribution map on the anterior wall for V_SAC of −10 mV and g_SAC = 0.04 mS/µF when λ_f was assumed constant and equal to 1.2. Pink dot indicates the location of the phase singularity.

Figure 6. Recruitment of SAC with V_SAC of −10 mV results in scroll wave breakup at large g_SAC.

(A): Distribution of λ_f at 0.9 s after arrhythmia induction for the ventricular model with V_SAC of −10 mV; g_SAC = 0.07 mS/µF. (B): Scroll wave breakup in the region of large stretch (indicated by arrow). (C), (D) and (E) are plots of I_SAC, I_Na and V_m, respectively from the node indicated by the arrow in (B). The arrow denotes in (C): the large inward I_SAC during repolarization, in (D): inactivation of Na channels, (E): conduction block.