Michael A Colman, Roshan Sharma, Oleg V Aslanidi, Jichao Zhao
{"title":"Patchy fibrosis promotes trigger-substrate interactions that both generate and maintain atrial fibrillation.","authors":"Michael A Colman, Roshan Sharma, Oleg V Aslanidi, Jichao Zhao","doi":"10.1098/rsfs.2023.0041","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13795,"journal":{"name":"Interface Focus","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722214/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Interface Focus","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1098/rsfs.2023.0041","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/6 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.