000063526 001__ 63526
000063526 005__ 20190709135625.0
000063526 0247_ $$2doi$$a10.3389/fbioe.2017.00029
000063526 0248_ $$2sideral$$a102852
000063526 037__ $$aART-2017-102852
000063526 041__ $$aeng
000063526 100__ $$0(orcid)0000-0003-4273-5403$$aSánchez, Carlos
000063526 245__ $$aAtrial fibrillation dynamics and ionic block effects in six heterogeneous human 3D virtual atria with distinct repolarization dynamics
000063526 260__ $$c2017
000063526 5060_ $$aAccess copy available to the general public$$fUnrestricted
000063526 5203_ $$aAtrial fibrillation (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 fiber 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 fibrillation 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. Specific 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 significant differences in atrial fibrillatory dynamics resulting from differences in APD at all phases of repolarization.
000063526 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/CIBER-BBN-MULTITOOLS2HEART$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-R$$9info:eu-repo/grantAgreement/ES/MINECO/TIN2013-41998-R
000063526 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000063526 592__ $$a1.565$$b2017
000063526 593__ $$aBioengineering$$c2017$$dQ1
000063526 593__ $$aHistology$$c2017$$dQ1
000063526 593__ $$aBiotechnology$$c2017$$dQ1
000063526 593__ $$aBiomedical Engineering$$c2017$$dQ1
000063526 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000063526 700__ $$aBueno-Orovio, Alfonso
000063526 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, Esther$$uUniversidad de Zaragoza
000063526 700__ $$aRodríguez, Blanca
000063526 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000063526 773__ $$g5, 29 (2017), 1-13$$pFront. Bioeng. Biotechnol.$$tFrontiers in Bioengineering and Biotechnology$$x2296-4185
000063526 8564_ $$s994635$$uhttps://zaguan.unizar.es/record/63526/files/texto_completo.pdf$$yVersión publicada
000063526 8564_ $$s105914$$uhttps://zaguan.unizar.es/record/63526/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000063526 909CO $$ooai:zaguan.unizar.es:63526$$particulos$$pdriver
000063526 951__ $$a2019-07-09-12:30:21
000063526 980__ $$aARTICLE