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bioRxiv · 10.1101/434456

Arrhythmia Mechanisms and Spontaneous Calcium Release: II - From Calcium Spark to Re-entry and Back

Colman, M. A.
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Abstract

MotivationThe role of sub-cellular spontaneous calcium release events (SCRE) in the development of arrhythmia associated with atrial and ventricular tachycardia and fibrillation has yet to be investigated in detail. SCRE may underlie the emergence of spontaneous excitation in single cells, resulting in arrhythmic triggers in tissue. Furthermore, they can promote the substrate for conduction abnormalities. However, the potential interactions with re-entrant excitation have yet to be explored. The primary aim of this study was therefore to apply a novel computational approach to understand the multi-scale coupling between re-entrant excitation and SCRE.\n\nMethodsA general implementation of Spontaneous Release Functions - which reproduce the calcium dependent SCRE dynamics of detailed cell models at a significantly reduced computational cost - was used to reproduce SCRE in tissue models. Arrhythmic dynamics, such as rapid pacing and re-entry, were induced in the tissue models and the resulting interactions with SCRE were analysed.\n\nResultsIn homogeneous tissue, the emergence of a spontaneous beat from a single source was observed and the positive role of coupling was demonstrated. Conduction block could be promoted by SCRE by both inactivation of the fast sodium channel as well as focal pacing heterogeneity interactions. Sustained re-entrant excitation promoted calcium overload, and led to the emergence of focal excitations both after termination of re-entry and also during re-entrant excitation. These results demonstrated a purely functional mechanism of re-entry and focal activity localisation, related to the unexcited spiral wave core.\n\nConclusionsSCRE may interact with tissue excitation to promote and perpetuate arrhythmia through multiple mechanisms, including functional localisation and mechanism switching. These insights may be particularly relevant for successful pharmacological management of arrhythmia.

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Colman, M. A.. 2018-10-03. Arrhythmia Mechanisms and Spontaneous Calcium Release: II - From Calcium Spark to Re-entry and Back. https://doi.org/10.1101/434456

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