Mechanisms of arrhythmogenesis related to calcium-driven alternans in a model of human atrial fibrillation

The occurrence of atrial fibrillation (AF) is associated with progressive changes in the calcium handling system of atrial myocytes. Calcium cycling instability has been implicated as an underlying mechanism of electrical alternans observed in patients who experience AF. However, the extent to which...

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Bibliographic Details
Published in:Scientific reports 2016-11, Vol.6 (1), p.36395-36395, Article 36395
Main Authors: Chang, Kelly C., Trayanova, Natalia A.
Format: Article
Language:English
Subjects:
631/57/2270/1140
639/166/985
Arrhythmia
Atrial Fibrillation - metabolism
Atrial Fibrillation - physiopathology
Calcium
Calcium - metabolism
Calcium Signaling
Calcium signalling
Cardiac arrhythmia
Fibrillation
Heart Atria - metabolism
Heart Atria - pathology
Heart Atria - physiopathology
Humanities and Social Sciences
Humans
Models, Cardiovascular
multidisciplinary
Myocytes
Propensity Score
Science
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Summary:The occurrence of atrial fibrillation (AF) is associated with progressive changes in the calcium handling system of atrial myocytes. Calcium cycling instability has been implicated as an underlying mechanism of electrical alternans observed in patients who experience AF. However, the extent to which calcium-induced alternation of electrical activity in the atria contributes to arrhythmogenesis is unknown. In this study, we investigated the effects of calcium-driven alternans (CDA) on arrhythmia susceptibility in a biophysically detailed, 3D computer model of the human atria representing electrical and structural remodeling secondary to chronic AF. We found that elevated propensity to CDA rendered the atria vulnerable to ectopy-induced arrhythmia. It also increased the complexity and persistence of arrhythmias induced by fast pacing, with unstable scroll waves meandering and frequently breaking up to produce multiple wavelets. Our results suggest that calcium-induced electrical instability may increase arrhythmia vulnerability and promote increasing disorganization of arrhythmias in the chronic AF-remodeled atria, thus playing an important role in the progression of the disease.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep36395