Atrial fibrillation in heart failure causes a large amount of death in the world. However, the mechanisms underlying atrial fibrillation in heart failure are not well understood. Atrial fibrillation and heart failure often coexist, and it is believed that there is a feedback connection between heart failure and atrial fibrillation. This thesis focuses on investigating the mechanisms underlying atrial fibrillation in heart failure by simulating a failing rabbit atrial model. Firstly, multiscale healthy and failing rabbit atrial electrophysiological models were developed by incorporating multiple experimental data sets, which can accurately reproduce the electrical activity in the healthy and failing rabbit atria. Then the developed models were used to explore the mechanisms underlying atrial fibrillation in heart failure. Simulation results showed that, in the failing atria, the action potential duration was larger in the pulmonary vein region than in the other regions, augmenting action potential duration (APD) heterogeneity. Such augmented APD heterogeneity facilitated the initiation of re-entry in the failing atria under a fast heart rate. As re-entry is believed to be one of the main mechanisms that maintain atrial fibrillation, our results demonstrate that the electrophysiological heterogeneity especially the long refractory period of the pulmonary vein region is responsible for initiating atrial fibrillation in heart failure. Our results provide new insights into the significant role of the pulmonary vein in heart failure.
|Date of Award
|31 Dec 2020
- The University of Manchester
|Henggui Zhang (Supervisor) & Mark Boyett (Supervisor)