Patchy fibrosis promotes trigger-substrate interactions that both generate and maintain atrial fibrillation.

IF 3.6 3区 生物学 Q1 BIOLOGY Interface Focus Pub Date : 2023-12-15 eCollection Date: 2023-12-06 DOI:10.1098/rsfs.2023.0041
Michael A Colman, Roshan Sharma, Oleg V Aslanidi, Jichao Zhao
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Abstract

Fibrosis has been mechanistically linked to arrhythmogenesis in multiple cardiovascular conditions, including atrial fibrillation (AF). Previous studies have demonstrated that fibrosis can create functional barriers to conduction which may promote excitation wavebreak and the generation of re-entry, while also acting to pin re-entrant excitation in stable rotors during AF. However, few studies have investigated the role of fibrosis in the generation of AF triggers in detail. We apply our in-house computational framework to study the impact of fibrosis on the generation of AF triggers and trigger-substrate interactions in two- and three-dimensional atrial tissue models. Our models include a reduced and efficient description of stochastic, spontaneous cellular triggers as well as a simple model of heterogeneous inter-cellular coupling. Our results demonstrate that fibrosis promotes the emergence of focal excitations, primarily through reducing the electrotonic load on individual fibre strands. This enables excitation to robustly initiate within these single strands before spreading to neighbouring strands and inducing a full tissue focal excitation. Enhanced conduction block can allow trigger-substrate interactions that result in the emergence of complex, re-entrant excitation patterns. This study provides new insight into the mechanisms by which fibrosis promotes the triggers and substrate necessary to induce and sustain arrhythmia.

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斑块状纤维化会促进触发器与底物之间的相互作用,从而产生并维持心房颤动。
纤维化与包括心房颤动(房颤)在内的多种心血管疾病的心律失常发生有着机理上的联系。以往的研究表明,纤维化会对传导造成功能性障碍,这可能会促进兴奋波的断裂和再入的产生,同时还能在房颤期间将再入兴奋抑制在稳定的转子中。然而,很少有研究详细调查了纤维化在房颤触发因素产生中的作用。我们运用内部计算框架研究了纤维化对房颤触发器生成的影响,以及二维和三维心房组织模型中触发器与基质之间的相互作用。我们的模型包括对随机、自发细胞触发器的简化和高效描述,以及异质细胞间耦合的简单模型。我们的研究结果表明,纤维化主要通过降低单个纤维股上的质子电负荷来促进局灶性激发的出现。这使得激振能在这些单股内稳健地启动,然后扩散到邻近的纤维股,并诱发整个组织的局灶激振。增强的传导阻滞可允许触发器与基底相互作用,从而产生复杂的再入激模式。这项研究为了解纤维化促进诱发和维持心律失常所需的触发器和基质的机制提供了新的视角。
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
Interface Focus
Interface Focus BIOLOGY-
CiteScore
9.20
自引率
0.00%
发文量
44
审稿时长
6-12 weeks
期刊介绍: Each Interface Focus themed issue is devoted to a particular subject at the interface of the physical and life sciences. Formed of high-quality articles, they aim to facilitate cross-disciplinary research across this traditional divide by acting as a forum accessible to all. Topics may be newly emerging areas of research or dynamic aspects of more established fields. Organisers of each Interface Focus are strongly encouraged to contextualise the journal within their chosen subject.
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