Mechanisms of Chemical Atrial Defibrillation by Flecainide and Ibutilide.

IF 8 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS JACC. Clinical electrophysiology Pub Date : 2024-09-13 DOI:10.1016/j.jacep.2024.08.009
Pei-Chi Yang, Luiz Belardinelli, Colleen E Clancy
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Abstract

Background: Effective and safe pharmacological approaches for atrial defibrillation offer several potential advantages over techniques like ablation. Pharmacological therapy is noninvasive, involving no risk associated with the procedure or resulting complications. Moreover, acute drug intervention with existing drugs is likely to be low cost and broadly accessible, thereby addressing a central tenet of health equity.

Objectives: This study aims to investigate ibutilide-mediated action potential prolongation to promote use-dependent effects of flecainide on Na+ channels by reducing the diastolic interval and, consequently, drug unbinding to reduce action potential excitability in atrial tissue and terminate re-entrant arrhythmia.

Methods: Here we utilize a modeling and simulation approach to predict the specific combinations of sodium- and potassium-channel blocking drugs to chemically terminate atrial re-entry.

Results: Computational modeling and simulation show that acute application of flecainide and ibutilide is a promising example of drug repurposing that may constitute a promising combination for chemical atrial defibrillation.

Conclusions: We predict the drug concentrations that promote efficacy of flecainide and ibutilide used in combination for atrial chemical defibrillation. We also predict the potential safety pharmacology impact of this drug combination on ventricular electrophysiology.

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氟卡尼和伊布利特的化学性心房除颤机制
背景:与消融等技术相比,有效、安全的心房除颤药物疗法具有多项潜在优势。药理疗法是非侵入性的,不会带来手术风险或并发症。此外,使用现有药物进行急性药物干预的成本可能很低,而且可以广泛使用,从而解决了健康公平的核心问题:本研究旨在研究伊布利特介导的动作电位延长,通过缩短舒张间期促进非加尼对 Na+ 通道的依赖性作用,从而使药物解除结合,降低心房组织中的动作电位兴奋性,终止再入性心律失常:计算建模和模拟显示,急性应用氟卡尼和伊布利特是药物再利用的一个很有希望的例子,可能构成化学性心房除颤的一种很有希望的组合:我们预测了氟卡尼和布替利联合用于心房化学除颤时促进疗效的药物浓度。我们还预测了这种药物组合对心室电生理学的潜在安全药理学影响。
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来源期刊
JACC. Clinical electrophysiology
JACC. Clinical electrophysiology CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
10.30
自引率
5.70%
发文量
250
期刊介绍: JACC: Clinical Electrophysiology is one of a family of specialist journals launched by the renowned Journal of the American College of Cardiology (JACC). It encompasses all aspects of the epidemiology, pathogenesis, diagnosis and treatment of cardiac arrhythmias. Submissions of original research and state-of-the-art reviews from cardiology, cardiovascular surgery, neurology, outcomes research, and related fields are encouraged. Experimental and preclinical work that directly relates to diagnostic or therapeutic interventions are also encouraged. In general, case reports will not be considered for publication.
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