May 2017 | Volume 5 | Article 29 1 ORIGINAL RESEARCH published: 08 May 2017 doi: 10.3389/fbioe.2017.00029 Frontiers in Bioengineering and Biotechnology | www.frontiersin.org Edited by: Joseph L. Greenstein, Johns Hopkins University, USA Reviewed by: Fadi G. Akar, Icahn School of Medicine at Mount Sinai, USA Thomas Hund, Ohio State University at Columbus, USA Edward Joseph Vigmond, University of Bordeaux 1, France *Correspondence: Carlos Sánchez cstapia@unizar.es Specialty section: This article was submitted to Computational Physiology and Medicine, a section of the journal Frontiers in Bioengineering and Biotechnology Received: 17 January 2017 Accepted: 18 April 2017 Published: 08 May 2017 Citation: Sánchez C, Bueno-Orovio A, Pueyo E and Rodríguez B (2017) Atrial Fibrillation Dynamics and Ionic Block Effects in Six Heterogeneous Human 3D Virtual Atria with Distinct Repolarization Dynamics. Front. Bioeng. Biotechnol. 5:29. doi: 10.3389/fbioe.2017.00029 Atrial Fibrillation Dynamics and Ionic Block Effects in Six Heterogeneous Human 3D Virtual Atria with Distinct Repolarization Dynamics Carlos Sánchez 1,2 *, Alfonso Bueno-Orovio 3 , Esther Pueyo 1,4 and Blanca Rodríguez 3 1 Biosignal Interpretation and Computational Simulation (BSICoS), I3A and IIS, University of Zaragoza, Zaragoza, Spain, 2 Defense University Centre (CUD), General Military Academy of Zaragoza (AGM), Zaragoza, Spain, 3 Department of Computer Science, University of Oxford, Oxford, UK, 4 Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain Atrial fbrillation (AF) usually manifests as reentrant circuits propagating through the whole atria creating chaotic activation patterns. Little is yet known about how differences in electrophysiological and ionic properties between patients modulate reentrant patterns in AF. The goal of this study is to quantify how variability in action potential duration (APD) at different stages of repolarization determines AF dynamics and their modulation by ionic block using a set of virtual whole-atria human models. Six human whole-atria models are constructed based on the same anatomical structure and fber orientation, but with different electrophysiological phenotypes. Membrane kinetics for each whole-atria model are selected with distinct APD characteristics at 20, 50, and 90% repolarization, from an experimentally calibrated population of human atrial action potential models, including AF remodeling and acetylcholine parasympathetic effects. Our simulations show that in all whole-atria models, reentrant circuits tend to organize around the pulmonary veins and the right atrial appendage, thus leading to higher dominant frequency (DF) and more organized activation in the left atrium than in the right atrium. Differences in APD in all phases of repolarization (not only APD90) yielded quantitative differences in fbrillation patterns with long APD associated with slower and more regular dynamics. Long APD50 and APD20 were associated with increased interatrial conduction block and interatrial differences in DF and organization index, creating reentry instability and self-termination in some cases. Specifc inhibitions of IK1, INaK, or INa reduce DF and organization of the arrhythmia by enlarging wave meandering, reducing the number of secondary wavelets, and promoting interatrial block in all six virtual patients, especially for the phenotypes with short APD at 20, 50, and/or 90% repolarization. This suggests that therapies aiming at prolonging the early phase of repolarization might constitute effective antiarrhythmic strategies for the pharmacological management of AF. In summary, simulations report signifcant differences in atrial fbrillatory dynamics resulting from differences in APD at all phases of repolarization. Keywords: arrhythmia, human atria, electrophysiology, variability, model populations, electrical propagation, fbrillatory patterns