Development of a Biophysically Detailed 3D Atrial Model for the Study of Cardiac Conduction.

Abstract

The heart is the most important organ in the human body. Without an optimally functioningheart, other organs soon fail and death ensues. Cardiovascular disease is theleading cause of death globally, accounting to 17.3 million deaths every year and thisnumber is expected to reach 23.6 million by 2030. A huge amount of resources arepooled annually for the study of the heart in order to gain a better understanding of theunderlying mechanisms involved in its function.Over the course of this project, a biophysically detailed, 3D computational modelof the rabbit atria has been developed. Previously published single cell models of therabbit atria served as a starting point and tissue heterogeneity was expanded by incorporatingnew experimental data and single cell models. Furthermore, a highly detailedanatomical reconstruction of the rabbit atria based on micro-CT imaging techniques aswell as realistic fibre orientation data extracted from this high resolution dataset wereincorporated into the 3D model. The project was successful in accurately representingthe physiology of the rabbit atrial function.Furthermore, a high resolution anatomical reconstruction of the atria from a rabbitwith experimental heart failure was used to study the effects of tissue hypertrophy,fibre disorganisation, tissue heterogeneity and ionic remodelling in cardiac function.It was found that tissue hypertrophy is a major contributor towards the increased riskassociated with heart failure through the promotion of re-entrant waves in the atria.Lastly, the role of the atrial septum in cardiac conduction was investigated. Throughthe use of 3D computational modelling, analysis of realistic fibre data extracted fromhigh resolution CT imaging as well as histological data, it was found that structures inthe atrial septum could play an important role in the propagation of electrical signalsfrom the atria towards the ventricles.

Date of Award	31 Dec 2016
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Henggui Zhang (Supervisor)