Hydroxychloroquine induces long QT syndrome by blocking hERG channel

作者：Xin Zhao, Lihua Sun, Chao Chen, Jieru Xin, Yan Zhang, Yunlong Bai, Zhenwei Pan, Yong Zhang, Baoxin Li, Yanjie Lv, Baofeng Yang · 发表于：Frigid Zone Medicine · 年份：2023 · DOI：10.2478/fzm-2023-0014 · 被引用次数：1 · 研究领域：Cardiac electrophysiology and arrhythmias、Ion channel regulation and function、Cardiac Arrest and Resuscitation

Abstract Objective In March 2022, more than 600 million cases of Corona Virus Disease 2019 (COVID-19) and about 6 million deaths have been reported worldwide. Unfortunately, while effective antiviral therapy has not yet been available, chloroquine (CQ)/hydroxychloroquine (HCQ) has been considered an option for the treatment of COVID-19. While many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients’ lives, controversial results have also been reported. One concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval (LQT), an electrophysiological substrate for the induction of lethal ventricular tachyarrhythmias. Yet, the mechanisms for this cardiotoxicity of HCQ remained incompletely understood. Materials and methods Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel genes. HEK-293T cells with sustained overexpression of human-ether-a-go-go-related gene (hERG) K + channels were used for whole-cell patch-clamp recordings of hERG K + channel current (I hERG ). Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels, respectively. Results electrocardiogram (ECG) recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in rabbits. Whole-cell patch-clamp results showed that HCQ inhibited th...