A novel computational sheep atria model for the study of atrial fibrillation

Abstract

One contribution of 25 to a Theme Issue 'The virtual physiological human: integrative approaches to computational biomedicine'. Sheep are often used as animal models for experimental studies into the underlying mechanisms of cardiac arrhythmias. Previous studies have shown that biophysically detailed computer models of the heart provide a powerful alternative to experimental animal models for underpinning such mechanisms. In this study, we have developed a family of mathematical models for the electrical action potentials of various sheep atrial cell types. The developed cell models were then incorporated into a three-dimensional anatomical model of the sheep atria, which was recently reconstructed and segmented based on anatomical features within different regions. This created a novel biophysically detailed computational model of the three-dimensional sheep atria. Using the model, we then investigated the mechanisms by which paroxysmal rapid focal activity in the pulmonary veins can transit to sustained atrial fibrillation. It was found that the anisotropic property of the atria arising from the fibre structure plays an important role in facilitating the development of fibrillatory atrial excitation waves, and the electrical heterogeneity plays an important role in its initiation.

Heterogeneous and anisotropic integrative model of pulmonary veins: computational study of arrhythmogenic substrate for atrial fibrillation

“…Shorter APDs in the PV than in the LA also agree with the experimental data [13]. Detailed comparisons between the AP characteristics simulated using the PV and LA models and measured experimentally can be found elsewhere [11,23].…”

“…Note also that the PV sleeves were segmented based on a histology-guided computational approach under the assumption that conduction pathways in the PVs are similar across species. Under this assumption, waves propagating with similar velocities in our canine model and the respective histology-based model of sheep atria [15,23] will cover a similar area over a similar time T act (see §2). The resultant PV segmentation in the canine model (figure 1b,c) agrees with histological [15] and anatomical [17] data, but needs further validation.…”

Effect of Heart Failure:induced Electrical Remodeling on the Initiation of Atrial Arrhythmias

“…We used a set of cellular models of sheep atrial myocytes developed by Butters et al [8] that took into considerations of the intrinsic electrophysiological Table 1) under HF based on the experiment data of the sheep [3]. As data from sheep may be incomplete, we also assumed similar changes of ICaL, Ito, IKs and INCX as shown in canine HF atrial cells [4,5] as shown in cases of HF-2 and HF-3 in Table 1.…”

“…The anatomically accurate and biophysically detailed 3D model of the sheep atria developed by Butters et al [8] was used in this study. In order to run the simulation of the 3D whole atrial model, we adopted the efficient GPU CUDA algorithm developed by Xia et al [9].…”

“…In this study, the effects of HF-induced changes of several ionic currents (ICaL, Ito, IKs, INCX) were based on experimental data of sheep or canine atria cells, which were incorporated into the sheep atrial cell model developed by Butters et al [8]. At the single cell level, effects of such HF-induced electrical remodeling on the action potential (AP) profile and APD as well as the intracellular Ca 2+ transient were evaluated.…”