Sudden cardiac death following cardiac arrest is a major killer in the industrialised world. The leading cause of sudden cardiac death are disturbances in the normal electrical activation of cardiac tissue, known as cardiac arrhythmia, which severely compromise the ability of the heart to fulfill the body's demand of oxygen. Ventricular fibrillation (VF) is the most deadly form of cardiac arrhythmia. Furthermore, electrical defibrillation through the application of strong electric shocks to the heart is the only effective therapy against VF. Over the past decades, a large body of research has dealt with the study of the mechanisms underpinning the success or failure of defibrillation shocks. The main mechanism of shock failure involves shocks terminating VF but leaving the appropriate electrical substrate for new VF episodes to rapidly follow (i.e. shock-induced arrhythmogenesis). A large number of models have been developed for the in silico study of shock-induced arrhythmogenesis, ranging from single cell models to three-dimensional ventricular models of small mammalian species. However, no extrapolation of the results obtained in the aforementioned studies has been done in human models of ventricular electrophysiology. The main reason is the large computational requirements associated with the solution of the bidomain equations of cardiac electrophysiology over large anatomically-accurate geometrical models including representation of fibre orientation and transmembrane kinetics. In this Thesis we develop simulation technology for the study of cardiac defibrillation in the human heart in the framework of the open source simulation environment Chaste. The advances include the development of novel computational and numerical techniques for the solution of the bidomain equations in large-scale high performance computing resources. More specifically, we have considered the implementation of effective domain decomposition, the development of new numerical techniques for the reduction of communication in Chaste's finite element method (FEM) solver, and the development of mesh-independent preconditioners for the solution of the linear system arising from the FEM discretisation of the bidomain equations. The developments presented in this Thesis have brought Chaste to the level of performance and functionality required to perform bidomain simulations with large three-dimensional cardiac geometries made of tens of millions of nodes and including accurate representation of fibre orientation and membrane kinetics. This advances have enabled the in silico study of shock-induced arrhythmogenesis for the first time in the human heart, therefore bridging an important gap in the field of cardiac defibrillation research.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:572834 |
| Date | January 2011 |
| Creators | Bernabeu Llinares, Miguel Oscar |
| Contributors | Pitt-Francis, Joe ; Rodriguez, Blanca ; Kay, David |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:9ca44896-8873-4c91-9358-96744e28d187 |
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