Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

Capel, Rebecca A.; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R.; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J.; Terrar, Derek A.; Burton, Rebecca Ann B.

doi:10.1016/j.hrthm.2015.05.027

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

Capel, Rebecca A.; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R.; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J.; Terrar, Derek A.; Burton, Rebecca Ann B.

Authors

Rebecca A. Capel

Neil Herring

Manish Kalla

Arash Yavari

Prof. GARY MIRAMS GARY.MIRAMS@NOTTINGHAM.AC.UK
Professor of Mathematical Biology

Gillian Douglas

Gil Bub

Keith Channon

David J. Paterson

Derek A. Terrar

Rebecca Ann B. Burton

Abstract

© 2015 Heart Rhythm Society. Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. Methods We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 μM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). Results In mouse atria, spontaneous beating rate was significantly (P

Citation

Capel, R. A., Herring, N., Kalla, M., Yavari, A., Mirams, G. R., Douglas, G., …Burton, R. A. B. (2015). Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential. Heart Rhythm, 12(10), 2186-2194. https://doi.org/10.1016/j.hrthm.2015.05.027

Journal Article Type	Article
Acceptance Date	May 27, 2015
Publication Date	Oct 1, 2015
Deposit Date	Jan 14, 2020
Publicly Available Date	Jan 24, 2020
Journal	Heart Rhythm
Print ISSN	1547-5271
Electronic ISSN	1556-3871
Publisher	Elsevier
Peer Reviewed	Peer Reviewed
Volume	12
Issue	10
Pages	2186-2194
DOI	https://doi.org/10.1016/j.hrthm.2015.05.027
Public URL	https://nottingham-repository.worktribe.com/output/3217439
Publisher URL	https://www.sciencedirect.com/science/article/pii/S154752711500630X