Effects of hydroxychloroquine on atrial electrophysiology in in silico wild-type and PITX2^+/- atrial cardiomyocytes.

IF 1.1 4区医学 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS

Herz Pub Date : 2023-10-01 Epub Date: 2023-02-02 DOI:10.1007/s00059-023-05162-w

Euijun Song

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引用次数: 0

Abstract

Background: Hydroxychloroquine (HCQ) is commonly used in the treatment of autoimmune diseases and increases the risk of QT interval prolongation. However, it is unclear how HCQ affects atrial electrophysiology and the risk of atrial fibrillation (AF).

Methods: We quantitatively examined the potential atrial arrhythmogenic effects of HCQ on AF using a computational model of human atrial cardiomyocytes. We measured atrial electrophysiological markers after systematically varying HCQ concentrations.

Results: The HCQ concentrations were positively correlated with the action potential duration (APD), resting membrane potential, refractory period, APD alternans threshold, and calcium transient alternans threshold (p < 0.05). By contrast, HCQ concentrations were inversely correlated with the maximum upstroke velocity and calcium transient amplitude (p < 0.05). When the therapeutic concentration (C_max) of HCQ was applied, HCQ increased APD₉₀ by 1.4% in normal sinus rhythm, 1.8% in wild-type AF, and 2.6% in paired-like homeodomain transcription factor 2 (PITX2)^+/- AF, but did not affect the alternans thresholds. The overall in silico results suggest no significant atrial arrhythmogenic effects of HCQ at C_max, instead implying a potential antiarrhythmic role of low-dose HCQ in AF. However, at an HCQ concentration of fourfold C_max, a rapid pacing rate of 4 Hz induced prominent APD alternans, particularly in the PITX2^+/- AF model.

Conclusion: Our in silico analysis suggests a potential antiarrhythmic role of low-dose HCQ in AF. Concomitant PITX2 mutations and high-dose HCQ treatments may increase the risk of AF, and this potential genotype/dose-dependent arrhythmogenic effect of HCQ should be investigated further.

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羟氯喹对矽肺野生型和PITX2+/-心房心肌细胞心房电生理的影响。

背景：羟氯喹（HCQ）通常用于治疗自身免疫性疾病，并增加QT间期延长的风险。然而，目前尚不清楚HCQ如何影响心房电生理学和心房颤动（AF）的风险。方法：我们使用人类心房心肌细胞的计算模型定量研究了HCQ对AF的潜在心房心律失常影响。在系统地改变HCQ浓度后，我们测量了心房电生理标志物。结果：HCQ浓度与动作电位持续时间（APD）、静息膜电位、不应期、APD交替阈值和钙瞬变阈值呈正相关（p 在正常窦性心律中，HCQ使APD90增加1.4%，在野生型AF中增加1.8%，在配对同源结构域转录因子2（PITX2）+/-AF中增加2.6%，但不影响交替阈值。总体的计算机结果表明，在Cmax浓度下，HCQ没有显著的致心房心律失常作用，相反，这意味着低剂量HCQ在房颤中具有潜在的抗心律失常作用。然而，在浓度为Cmax四倍的HCQ下，4 Hz引起显著的APD交替，特别是在PITX2+/-AF模型中。结论：我们的计算机分析表明，低剂量HCQ在房颤中具有潜在的抗心律失常作用。伴随PITX2突变和高剂量HCQ治疗可能会增加房颤的风险，应进一步研究HCQ的这种潜在基因型/剂量依赖性心律失常效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Herz 医学-心血管系统

CiteScore

3.00

自引率

5.90%

发文量

审稿时长

4-8 weeks

期刊介绍： Herz is the high-level journal for further education for all physicians interested in cardiology. The individual issues of the journal each deal with specific topics and comprise review articles in English and German written by competent and esteemed authors. They provide up-to-date and comprehensive information concerning the speciality dealt with in the issue. Due to the fact that all relevant aspects of the pertinent topic of an issue are considered, an overview of the current status and progress in cardiology is presented. Reviews and original articles round off the spectrum of information provided.