The antimalarial chloroquine reduces the burden of persistent atrial fibrillation

Catalina Tobón, Laura C. Palacio, Bojjibabu Chidipi, Diana P. Slough, Thanh Tran, Nhi Tran, Michelle Reiser, Yu Shan Lin, Bengt Herweg, Dany Sayad, Javier Saiz, Sami Noujaim

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish
Article number1392
JournalFrontiers in Pharmacology
Volume10
DOIs
StatePublished - 1 Jan 2019

Keywords

  • Chloroquine
  • I
  • Persistent atrial fibrillation
  • Potassium inward rectifiers

Fingerprint Dive into the research topics of 'The antimalarial chloroquine reduces the burden of persistent atrial fibrillation'. Together they form a unique fingerprint.

  • Cite this

    Tobón, C., Palacio, L. C., Chidipi, B., Slough, D. P., Tran, T., Tran, N., Reiser, M., Lin, Y. S., Herweg, B., Sayad, D., Saiz, J., & Noujaim, S. (2019). The antimalarial chloroquine reduces the burden of persistent atrial fibrillation. Frontiers in Pharmacology, 10, [1392]. https://doi.org/10.3389/fphar.2019.01392