Abstract:

Cardiac arrhythmia is currently investigated from two different points of view. One considers ECG bio-signal analysis and investigates heart rate variability, baroreflex control, heart rate turbulence, alternans phenomena, etc. The other involves building computer models of the heart based on ion channels, bio-domain models and forward calculations to finally reach ECG and body surface potential maps. Both approaches aim to support the cardiologist in better understanding of arrhythmia, improving diagnosis and reliable risk stratification, and optimizing therapy. This article summarizes recent results and aims to trigger new research to bridge the different views.

Abstract:

Investigating the mechanisms underlying the genesis and conduction of electrical excitation in the atria at physiological and pathological states is of great importance. To provide knowledge concerning the mechanisms of excitation, we constructed a biophysical detailed and anatomically accurate computer model of human atria that incorporates both structural and electrophysiological heterogeneities. The three-dimensional geometry was extracted from the visible female dataset. The sinoatrial node (SAN) and atrium, including crista terminalis (CT), pectinate muscles (PM), appendages (APG) and Bachmann's bundle (BB) were segmented in this work. Fibre orientation in CT, PM and BB was set to local longitudinal direction. Descriptions for all used cell types were based on modifications of the Courtemanche et al. model of a human atrial cell. Maximum conductances of Ito, IKr and ICa,L were modified for PM, CT, APG and atrioventricular ring to reproduce measured action potentials (AP). Pacemaker activity in the human SAN was reproduced by removing IK1, but including If, ICa,T, and gradients of channel conductances as described in previous studies for heterogeneous rabbit SAN. Anisotropic conduction was computed with a monodomain model using the finite element method. The transversal to longitudinal ratio of conductivity for PM, CT and BB was 1:9. Atrial working myocardium (AWM) was set to be isotropic. Simulation of atrial electrophysiology showed initiation of APs in the SAN centre. The excitation spread afterwards to the periphery near to the region of the CT and preferentially towards the atrioventricular region. The excitation extends over the right atrium along PM. Both CT and PM activated the right AWM. Earliest activation of the left atrium was through BB and excitation spread over to the APG. The conduction velocities were 0.6ms-1 for AWM, 1.2ms-1 for CT, 1.6ms-1 for PM and 1.1ms-1 for BB at a rate of 63bpm. The simulations revealed that bundles form dominant pathways for atrial conduction. The preferential conduction towards CT and along PM is comparable with clinical mapping. Repolarization is more homogeneous than excitation due to the heterogeneous distribution of electrophysiological properties and hence the action potential duration.

Abstract:

Atrial fibrillation (AF) is a common cardiac disease with high rates of morbidity, leading to major personal and NHS costs. Computer modeling of AF using a detailed cellular model with realistic 3D anatomical geometry allows investigation of the underlying ionic mechanisms in far more detail than in a physiology laboratory. We have developed a 3D virtual human atrium that combines detailed cellular electrophysiology, including ion channel kinetics and homeostasis of ionic concentrations, with anatomical detail. The segmented anatomical structure and multi-variable nature of the system makes the 3D simulations of AF large and computationally intensive. The computational demands are such that a full problem solving environment requires access to resources of High Performance Computing (HPC), High Performance Visualization (HPV), remote data repositories and a backend infrastructure. This is a classic example of eScience and Gridenabled computing. Initial work has been carried out using multiple processor machines with shared memory architectures. As spatial resolution of anatomical models increases, requirement of HPC resources is predicted to increase many-fold ( ~ 1 10 teraflops). Distributed computing is essential, both through massively parallel systems (a single supercomputer) and multiple parallel systems made accessible through the Grid.