@article{2f07a27c756c4b69b6857de99940e507,
title = "The antimalarial chloroquine reduces the burden of persistent atrial fibrillation",
abstract = "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 (IK1 and IKACh) could be antiarrhythmic in persistent atrial fibrillation. We thus tested the hypothesis that blocking IK1 and IKACh with chloroquine decreases the burden of persistent atrial fibrillation. We used patch clamp to determine the IC50 of IK1 and IKACh block by chloroquine and molecular modeling to simulate the interaction between chloroquine and Kir2.1 and Kir3.1, the molecular correlates of IK1 and IKACh. 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 IK1 block by chloroquine was similar to that of IKACh. 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 IK1 and IKACh can be a targeted therapeutic strategy for persistent atrial fibrillation.",
keywords = "Chloroquine, I, Persistent atrial fibrillation, Potassium inward rectifiers",
author = "Catalina Tob{\'o}n and Palacio, {Laura C.} and Bojjibabu Chidipi and Slough, {Diana P.} and Thanh Tran and Nhi Tran and Michelle Reiser and Lin, {Yu Shan} and Bengt Herweg and Dany Sayad and Javier Saiz and Sami Noujaim",
note = "Funding Information: This work was supported in part by National Institutes of Health grants R21HL138064, R01HL129136, by the Direcci?n General de Pol?tica Cient?fica de la Generalitat Valenciana (PROMETEO 2016/088), and by the ACM SIGHPC/Intel Computational & Data Science fellowship. Funding Information: This work was supported in part by National Institutes of Health grants R21HL138064, R01HL129136, by the Direcci{\'o}n General de Pol{\'i}tica Cient{\'i}fica de la Generalitat Valenciana (PROMETEO 2016/088), and by the ACM SIGHPC/Intel Computational & Data Science fellowship. Publisher Copyright: Copyright {\textcopyright} 2019 Tob{\'o}n, Palacio, Chidipi, Slough, Tran, Tran, Reiser, Lin, Herweg, Sayad, Saiz and Noujaim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",
year = "2019",
month = jan,
day = "1",
doi = "10.3389/fphar.2019.01392",
language = "Ingl{\'e}s",
volume = "10",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media S.A.",
}