Investigation of the Role of Myocyte Orientations in Cardiac Arrhythmia Using Image-Based Models

Abstract

Cardiac electrical excitation-propagation is influenced by myocyte orientations (cellular organization). Quantitatively understanding this relationship presents a significant research challenge, especially during arrhythmias in which excitation patterns become complex. Tissue-scale simulations of cardiac electrophysiology, incorporating both dynamic action potential behavior and image-based myocardial architecture, provide an approach to investigate three-dimensional (3D) propagation of excitation waves in the heart. In this study, we aimed to assess the importance of natural variation in myocyte orientations on cardiac arrhythmogenesis using 3D tissue electrophysiology simulations. Three anatomical models (i.e., describing myocyte orientations) of healthy rat ventricles—obtained using diffusion tensor imaging at 100 μ m resolution—were registered to a single biventricular geometry (i.e., a single cardiac shape), in which the myocyte orientations could be represented by each of the diffusion tensor imaging data sets or by an idealized rule-based description. The Fenton-Karma cellular excitation model was modified to reproduce rat ventricular action potential duration restitution to create reaction-diffusion cardiac electrophysiology models. Over 250 3D simulations were performed to investigate the effects of myocyte orientations on the following: 1) ventricular activation, 2) location-dependent arrhythmia induction via rapid pacing, and 3) dynamics of re-entry averaged over multiple episodes. It was shown that 1) myocyte orientation differences manifested themselves in local activation times, but the influence on total activation time was small; 2) differences in myocyte orientations could critically affect the inducibility and persistence of arrhythmias for specific stimulus-location/cycle-length combinations; and 3) myocyte orientations alone could be an important determinant of scroll wave break, although no significant differences were observed in averaged arrhythmia dynamics between the four myocyte orientation scenarios considered. Our results show that myocyte orientations are an important determinant of arrhythmia inducibility, persistence, and scroll wave break. These findings suggest that where specificity is desired (for example, when predicting location-dependent, patient-specific arrhythmia inducibility), subject-specific myocyte orientations may be important.

Calibration of ionic and cellular cardiac electrophysiology models

“…Fenton and Karma ( 1998 ) presented a minimal ionic model with three membrane currents (controlled by three gating variables) which was able to reproduce the restitution and spiral wave behavior of more complex AP models. The simplicity of the model means that it is readily adaptable to reproduce the activity of new models and cell types (Oliver & Krassowska, 2005 ; Podziemski & Żebrowski, 2013 ; Whittaker, Benson, Teh, Schneider, & Colman, 2019 ). However, although the Fenton and Karma ( 1998 ) model was able to reproduce APD and CV restitution curves, it could not reproduce different AP shapes, such as a “spike‐and‐dome” morphology, accurately.…”

Anatomical Model of Rat Ventricles to Study Cardiac Arrhythmias under Infarction Injury

“…For 3D simulations, we used the anatomical model of the rat ventricular geometry and the fiber orientation from [16] (https://github.com/DGWhittaker/Rat-FK3V-files/ tree/master/Geometry-files accessed on 26 September 2021.) MH1 fiber orientation).…”

“…Considering animal cardiac models, models of rabbit [11,14], dog [12], and swine [15] hearts already exist. Despite the rat being the most widely used laboratory animal, speciesspecific computer models of the rat heart are limited [13,16,17]. In most cases, existing computational models describe healthy normal hearts.…”

The Heart by Numbers

“…This anatomical arrangement, which translates a linear 20% shortening of fibers into an ejection of 60% of chamber volume, yields a biomechanics/biofluids problem of great beauty and immense complexity (1,2). With each beat, the fibers of the heart wall contract in a temporally and spatially coordinated manner, governed by a specialized network of muscle fibers propagating electrical signals throughout the myocardium (3)(4)(5)(6)(7). At the microscopic level, electrical phenomena elicit chemical signals to the molecular machinery of contraction (8,9).…”

“…Transitioning to tissue and organ-level electrophysiology, four papers use finite element techniques to investigate how action potentials spread through the heart. The first paper by Whittaker et al (7) studies the potential impact of myocyte orientation. By running simulations where cardiac cells are packed into a single biventricular geometry in different ways, they show that myocyte orientation affects the inducibility and persistence of arrhythmias and could be an important determinant of scroll wave-break.…”