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[EN] Atrial fibrillation (AF) is the most common tachyarrhythmia. It has been demonstrated that extra-stimuli could act as triggers for AF. In many patients it is possible that multiple ectopic foci co-exist, and their interactions may generate complex conduction patterns. Our goal is to investigate the influence of the focus frequency, conduction velocity, and anisotropy on fibrillatory pattern generation during the interaction of multiple ectopic activities under electrical remodeling conditions. Our results support the broadly accepted theory that ectopic activity acting in remodeled tissue is an initiator of reentrant mechanisms. These reentrant circuits can generate fibrillatory activity when interacting with other rapid ectopic foci and under the following conditions: high ectopic focus frequency, slow conduction velocity, and anisotropic tissue. Analyses of electrogram polymorphism allow determination of which zones of tissue permit one to know in which zone of tissue unstable activity exists. Our results give useful insights into the electrophysiological parameters that determine the initiation and maintenance of fibrillatory conduction by two ectopic foci interaction in a simulated two-dimensional sheet of human atrial cells, under chronic AF conditions. ; This work was partially supported by the Direccion General de Politica Cientifica de la Generalitat Valenciana (PROMETEU 2016/088) and the University of Medellin ; Tobón, C.; Saiz Rodríguez, FJ. (2019). Fibrillatory conduction in a simulated two-dimensional model of human atrial tissue: effect of the interaction of two ectopic foci. Transactions of the Society for Computer Simulation. 95(7):577-591. https://doi.org/10.1177/0037549718782401 ; S ; 577 ; 591 ; 95 ; 7 ; Fuster, V., Rydén, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., … Ellenbogen, K. A. (2006). ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation—Executive Summary. Circulation, 114(7), 700-752. doi:10.1161/circulationaha.106.177031 ; Stewart, S., ...

[EN] In clinical practice, reducing the burden of persistent atrial fibrillation by pharmacological means is challenging. We explored if blocking the background and the acetylcholine-activated inward rectifier potassium currents (I-K1 and I-KACh) could be antiarrhythmic in persistent atrial fibrillation. We thus tested the hypothesis that blocking I-K1 and I-KACh with chloroquine decreases the burden of persistent atrial fibrillation. We used patch clamp to determine the IC50 of I-K1 and I-KACh block by chloroquine and molecular modeling to simulate the interaction between chloroquine and Kir2.1 and Kir3.1, the molecular correlates of I-K1 and I-KACh. We then tested, as a proof of concept, if oral chloroquine administration to a patient with persistent atrial fibrillation can decrease the arrhythmia burden. We also simulated the effects of chloroquine in a 3D model of human atria with persistent atrial fibrillation. In patch clamp the IC50 of I-K1 block by chloroquine was similar to that of I-KACh. A 14-day regimen of oral chloroquine significantly decreased the burden of persistent atrial fibrillation in a patient. Mathematical simulations of persistent atrial fibrillation in a 3D model of human atria suggested that chloroquine prolonged the action potential duration, leading to failure of reentrant excitation, and the subsequent termination of the arrhythmia. The combined block of I-K1 and I-KACh can be a targeted therapeutic strategy for persistent atrial fibrillation. ; This work was supported in part by National Institutes of Health grants R21HL138064, R01HL129136, by the Direccion General de Politica Cientifica de la Generalitat Valenciana (PROMETEO 2016/088), and by the ACM SIGHPC/Intel Computational & Data Science fellowship. ; Tobón, C.; Palacio, LC.; Chidipi, B.; Slough, DP.; Tran, T.; Tran, N.; Reiser, M. (2019). The Antimalarial Chloroquine Reduces the Burden of Persistent Atrial Fibrillation. Frontiers in Pharmacology. 10:1-12. https://doi.org/10.3389/fphar.2019.01392 ; S ; 1 ; 12 ; 10 ...