Development of a biophysically detailed 3D atrial model for the study of cardiac conduction

• Main Author: Kottas, Petros
• Published: University of Manchester 2016
• Subjects: 500
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727942

The heart is the most important organ in the human body. Without an optimally functioning heart, other organs soon fail and death ensues. Cardiovascular disease is the leading cause of death globally, accounting for 17.3 million deaths every year and this number is expected to reach 23.6 million by 2030. A huge amount of resources are pooled annually for the study of the heart in order to gain a better understanding of the underlying mechanisms involved in its function. Over the course of this project, a biophysically detailed, 3D computational model of the rabbit atria has been developed. Previously published single cell models of the rabbit atria served as a starting point and tissue heterogeneity was expanded by incorporating new experimental data and single cell models. Furthermore, a highly detailed anatomical reconstruction of the rabbit atria based on micro-CT imaging techniques as well as realistic fibre orientation data extracted from this high resolution dataset were incorporated into the 3D model. The project was successful in accurately representing the physiology of the rabbit atrial function. Furthermore, a high resolution anatomical reconstruction of the atria from a rabbit with 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 risk associated 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. Through the use of 3D computational modelling, analysis of realistic fibre data extracted from high resolution CT imaging as well as histological data, it was found that structures in the atrial septum could play an important role in the propagation of electrical signals from the atria towards the ventricles.