Search

The use of anti-arrhythmic drugs is common to treat heart rhythm disorders. Computational modeling and simulation are powerful tools that can be used to investigate the effects of specific drugs on cardiac electrophysiology. In this work a patient-specific anatomical heart model is built to study the effects of dofetilide, a drug that affects IKr current in cardiac cells. We study the multi-scale effects of the drug, from cellular to organ level, by simulating electrical propagation on tissue coupled cellular ion kinetics for several heart beats. Different cell populations configurations namely endocardial, midmyocardial and epicardial are used to test the effect of tissue heterogeneity. Results confirmed the expected effects of dofetilide at cellular level, increasing the action potential duration. Pseudo-ECGs obtained for each heart beat correlated well with cellular results showing prolongation of QT segment. These techniques can be applied over the development of more complex drugs that affect multiple cellular currents. [ABSTRACT FROM AUTHOR]

The modeling of the electrical activity of the heart is of great medical and scientific interest, because it provides a way to get a better understanding of the related biophysical phenomena, allows the development of new techniques for diagnoses and serves as a platform for drug tests. The cardiac electrophysiology may be simulated by solving a partial differential equation (PDE) coupled to a system of ordinary differential equations (ODEs) describing the electrical behavior of the cell membrane. The numerical solution is, however, computationally demanding because of the fine temporal and spatial sampling required. The demand for real time high definition 3D graphics made the new graphic processing units (GPUs) a highly parallel, multithreaded, many-core processor with tremendous computational horsepower. It makes the use of GPUs a promising alternative to simulate the electrical activity in the heart. The aim of this work is to study the performance of the use of GPUs to solve the equations underlying the electrical activity in a simple cardiac tissue. [ABSTRACT FROM AUTHOR]

Whole heart computer models are being widely used to assess treatment planning like Cardiac Resynchronization Therapy (CRT), a recognized treatment for heart failure. Certain aspects like cardiac geometry and the Purkinje system (PS) are still sometimes neglected on the studies. The present study includes a model of the human ventricles with incorporated anatomical structures such as myofibers orientation and Purkinje system. Two meshes representative of hypertrophic and dilated cardiomyopathies were generated from an original healthy subject mesh. In the context of (III) atrio-ventricular (AV) block, a sequential pacing protocol was tested for different device configurations. The pacing protocols were performed in models including the PS and in models lacking the PS. The results show that the Purkinje System leads to the synchronization of the septum and the left ventricle (LV) lateral wall, thus minimizing the interventricular delay. Also the modifications in the geometry resulted in changes in the activation patterns of the LV lateral wall, differing notably from physiological scenario. [ABSTRACT FROM AUTHOR]

The anisotropic electrical conduction within myocardial tissue due to preferential cardiac myocyte orientation (`fibre orientation) is known to impact strongly in electrical wavefront dynamics, particularly during arrhythmogenesis. Faithful representation of cardiac fibre architecture within computational cardiac models which seek to investigate such phenomena is thus imperative. Drawbacks in derivation of fibre structure from imaging modalities often render rule-based representations based on a priori knowledge preferential. However, the validity of using such rule-based approaches within whole ventricular models remains unclear. Here, we present the development of a generic computational framework to directly compare the fibre architecture predicted by rule-based methods used within whole ventricular models against fibre structure derived from DTMRI data, and assess how relative differences influence propagation dynamics throughout the ventricles. Results demonstrate the close overall match between the methods within the rat ventricles, and highlight regions for potential rule-adaption. [ABSTRACT FROM AUTHOR]

Recent experimental findings have suggested the important role played by blood vessels within the heart in stabilising arrhythmias. However, this link has yet to be explored computationally. In this paper, we develop a computational framework to model fibre orientation around structural inhomogeneities in myocardial tissue based on information obtained from high-resolution histological and MRI images. This framework allows the simulation of cardiac wavefront propagation for a generalised vessel orientation and position within the ventricular wall and transmural fibre architecture around it. We simulate propagation following different stimulation protocols around a transmural and a sub-epicardial vessel, using both bidomain and monodomain representations. We demonstrate the importance of accurately modelling the fibre structure around blood vessels relative to a simplistic transmurally varying fibre orientation model and suggest how this may impact pro-arrhythmic electrical dynamics. [ABSTRACT FROM AUTHOR]

The purpose of this computational study was to test the pertinence of the magnitude of the minimum time derivative of the extracellular potential, |dVes/dtmin|, measured in a thin, conducting solution layer adjacent to the tissue, as an index of cardiac excitability. For this purpose, we performed computational studies characterizing the relationship between |dVes/dtmin| and the maximum upstroke velocity of transmembrane voltage, dVm/dtmax, which has been used in previous studies as an index of excitability. A three-dimensional bidomain model of electrical conduction in cardiac tissue was used based on the Noble-Varghese-Kohl-Noble model of ventricular myocytes. The spatial domain included a slab of cardiac tissue with intra- and extracellular anisotropic conductivities surrounded by a layer of solution. The simulations showed linear relationships between |dVes/dtmin| and dVm/dtmax for reduction of maximum sodium current conductance (GNa) from 100% to 20%. The relationship was dependent on location and propagation direction. However, when both parameters were normalized, those dependencies disappeared. In summary, our study demonstrated that normalized |dVes/dtmin| is linearly related to normalized dVm/dtmax. The results support our hypothesis that normalized |dVes/dtmin| can be used as an index of cardiac excitability. [ABSTRACT FROM AUTHOR]