Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, PC99

Poster Communications

Role of the Pulmonary Vein in the Genesis of Atrial Fibrillation: Insights from a Biophysically Detailed Computational Model

O. V. Aslanidi1, G. Gupta1, L. Foster1, M. R. Boyett2, H. Zhang1

1. School of Physics & Astronomy, University of Manchester, Manchester, United Kingdom. 2. Faculty of Medical & Human Sciences, University of Manchester, Manchester, United Kingdom.


Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, as well as the major cause of stroke. Several lines of evidence point to a particularly important role of the left atrium (LA) in maintaining AF [1]. Primarily, it has been suggested that "driver" regions within the LA, which act as high-frequency excitation sources during AF, are localized around sleeves of the pulmonary vein (PV) [2]. However, mechanisms by which latently pacemaking cells of the PV can initiate/maintain AF are unclear. We study such mechanisms using an electrophysiologically detailed 3D tissue model of rabbit atria. Single cell action potential (AP) models for rabbit atrial cells have been developed previously, which include left and right atrial (LA and RA) cells [3], cells of the RA bundles of the crista terminalis (CT) and pectinate muscles (PM) [4], cells forming two major inter-atrial connections through the Bachmann's bundle (BB) and coronary sinus (CS) [5], and pacemaking cells of the PV. All single cell models were incorporated into a caricature 3D geometry comprising square LA and RA tissues, two intra- (CT and PM) and two inter-atrial (BB and CS) conductive bundles and a cylindrical PV entering the LA. The resultant 3D model was used to simulate excitation wave patterns within the atria: (i) propagation of periodic APs ("normal rhythm") onto the PV; (ii) emergence of an ectopic wave source due to spontaneous AP firing within the PV; (iii) interaction of reentrant spiral waves with the PV. Interaction of periodic waves (period of ~800 ms) - which simulated slow normal rhythm - with ectopic APs generated within the PV led to wave break down and development of reentrant spiral waves. However, the intrinsically slow ectopic source in the PV (firing period of ~700 ms) was suppressed by either rotating spiral waves (period of ~100 ms) or periodic waves during the normal rhythm (period of <600 ms). Besides, the spiral waves were unpinned from the PV for normal physiological values of the PV parameters (such as dimensions and intercellular coupling values) - but became pinned to the PV for the parameter values corresponding to dilated tissue. Hence, (1) an ectopic wave source within the PV can develop under bradycardic condition and play a role in AF initiation, and (2) the PV may be involved in maintaining high-frequency reentrant sources during AF when the heart is dilated. In summary, our 3D atrial tissue model provides mechanistic insights into the role of the PV in the genesis of AF, primarily conditions for the initiation of ectopic APs breaking down the normal rhythm and the maintenance of the fibrillatory state.

Where applicable, experiments conform with Society ethical requirements