Development of a Virtual 3D Sheep Atria for the Study of Clinical Atrial Fibrillation

Abstract

Cardiovascular disease remains the leading cause of death in the developed world.In this thesis computational modelling techniques were used to study the mech-anisms and genesis of atrial arrhythmias. It is separated into 2 parts:(1) The mechanistic links between mutations of the fast Na+ channel (INa )and the ability of the sinoatrial node to pace the surrounding atrial muscle wereinvestigated. The mutations were separated into two groups, one for the mu-tations affecting the steady-state activation, and the other for those affectingsteady-state inactivation. On the single cell level it was found that all mutationsslowed the pacing rate of the sinoatrial node in a similar way, but at the 2D levelthe two mutation groups modulated the excitation of the tissue differently. Onecaused a conduction block between the sinoatrial node and atrium, where theother abolished pacemaking all together.(2) A new set of mathematical models were then developed for the sheep atria.This was incorporated into an anatomically detailed 3D geometry of the wholesheep atria to form a platform suitable for the study of clinical atrial fibrillation,and other atrial arrhythmias. Due to the lack of single cell electrophysiologydata available, a method of cross-species modelling was utilised. A biophysicallydetailed model of the 3D sheep atria was created, and used in a preliminary studyinto the susceptibility of tissue to atrial fibrillation from the rapid pacing of thepulmonary vein area. It was found that both electrical heterogeneity and thecomplex fibre structure of the atria need to be considered for sustained atrialfibrillation to be seen.

Date of Award	1 Aug 2012
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Henggui Zhang (Supervisor)