Article
Ventricular endocardial tissue geometry influences stimulus threshold and effective refractory period

Abstract

Background

Understanding the biophysical processes by which electrical stimuli applied to cardiac tissue may result in local activation is important in both the experimental and clinical electrophysiology laboratory environments, as well as gaining a more in-depth knowledge of the mechanisms of focal trigger-induced arrhythmias. Previous computational models have predicted that local myocardial tissue architecture alone may significantly modulate tissue excitability, affecting both the local stimulus current required to excite the tissue and the local effective refractory period (ERP). In this work, we present experimental validation of this structural modulation of local tissue excitability on the endocardial tissue surface, and use computational models to provide mechanistic understanding of this phenomena in relation to localised changes in electrotonic loading, and demonstrate its implications for the capture of afterdepolarisations.

Methods

Results: Experiments on rabbit ventricular wedge preparations showed that endocardial ridges (surfaces of negative mean curvature) had a stimulus capture threshold that was 0.21±0.03 V less than endocardial grooves (surfaces of positive mean curvature) for pairwise comparison (24% reduction, corresponding to 56.2±6.4 % of the energy). When stimulated at the minimum stimulus strength for capture, ridge locations showed a shorter ERP than grooves (n=6, mean pairwise difference 7.4±4.2 ms). When each site was stimulated with identical strength stimuli, the difference in ERP was further increased (mean pairwise difference 15.8±5.3 ms). Computational bidomain models of highly idealized cylindrical endocardial structures qualitatively agreed with these findings, showing that such changes in excitability are driven by structural modulation in electrotonic loading, quantifying this relationship as a function of surface curvature. Simulations further showed that capture of delayed afterdepolarisations was more likely in trabecular ridges than grooves, driven by this difference in loading.

Conclusions

We have demonstrated experimentally, and explained mechanistically in computer simulations, that the ability to capture tissue on the endocardial surface depends upon the local tissue architecture. These findings have important implications for deepening our understanding of excitability differences related to anatomical structure during stimulus application that may have important applications in the translation of novel experimental optogenetics pacing strategies. The uncovered preferential vulnerability to capture of afterdepolarisations of endocardial ridges, compared to grooves, provides important insight for understanding the mechanisms of focal trigger-induced arrhythmias.

These authors contributed equally

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