Niort Barbara C, Recalde Alice, Cros Caroline, Brette Fabien
Centre de Recherche Cardio-Thoracique de Bordeaux (CRCTB), Inserm U1045, Univeristé de Bordeaux, F-33000 Bordeaux, France.
IHU Liryc, Electrophysiology and Heart Modeling Institute, F-33600 Pessac, France.
J Clin Med. 2023 Jan 17;12(3):746. doi: 10.3390/jcm12030746.
Atrial fibrillation is the most sustained form of arrhythmia in the human population that leads to important electrophysiological and structural cardiac remodeling as it progresses into a chronic form. Calcium is an established key player of cellular electrophysiology in the heart, yet to date, there is no information that maps calcium signaling across the left atrium.
The aim of this study is to determine whether calcium signaling is homogenous throughout the different regions of the left atrium. This work tests the hypothesis that differences across the healthy left atrium contribute to a unique, region-dependent calcium cycling and participates in the pro-arrhythmic activity during atrial fibrillation.
An animal model relevant to human cardiac function (the sheep) was used to characterize both the electrical activity and the calcium signaling of three distinct left atrium regions (appendage, free wall and pulmonary veins) in control conditions and after acetylcholine perfusion (5 μM) to induce acute atrial fibrillation. High-resolution dual calcium-voltage optical mapping on the left atria of sheep was performed to explore the spatiotemporal dynamics of calcium signaling in relation to electrophysiological properties.
Action potential duration (at 80% repolarization) was not significantly different in the three regions of interest for the three pacing sites. In contrast, the time to 50% calcium transient decay was significantly different depending on the region paced and recorded. Acetylcholine perfusion and burst pacing-induced atrial fibrillation when pulmonary veins and appendage regions were paced but not when the free wall region was. Dantrolene (a ryanodine receptor blocker) did not reduce atrial fibrillation susceptibility.
These data provide the first evidence of heterogenous calcium signaling across the healthy left atrium. Such basal regional differences may be exacerbated during the progression of atrial fibrillation and thus play a crucial role in focal arrhythmia initiation without ryanodine receptor gating modification.
心房颤动是人类最常见的持续性心律失常形式，随着其发展为慢性形式，会导致重要的心脏电生理和结构重塑。钙是心脏细胞电生理中公认的关键因素，但迄今为止，尚无关于左心房钙信号传导图谱的信息。
本研究旨在确定钙信号在左心房不同区域是否均匀。这项工作检验了以下假设：健康左心房各区域的差异导致独特的、区域依赖性的钙循环，并参与心房颤动期间的促心律失常活动。
使用与人类心脏功能相关的动物模型（绵羊），在对照条件下以及乙酰胆碱灌注（5 μM）诱导急性心房颤动后，对三个不同的左心房区域（心耳、游离壁和肺静脉）的电活动和钙信号进行表征。对绵羊左心房进行高分辨率双钙电压光学映射，以探索与电生理特性相关的钙信号的时空动态。
对于三个起搏部位，三个感兴趣区域的动作电位持续时间（复极化80%时）无显著差异。相比之下，钙瞬变衰减至50%的时间根据起搏和记录的区域而有显著差异。当肺静脉和心耳区域起搏时，乙酰胆碱灌注和短阵快速起搏可诱发心房颤动，但游离壁区域起搏时则不会。丹曲林（一种兰尼碱受体阻滞剂）并未降低心房颤动的易感性。
这些数据首次证明了健康左心房存在异质性钙信号传导。这种基础区域差异在心房颤动进展过程中可能会加剧，从而在不改变兰尼碱受体门控的情况下，在局灶性心律失常的起始中起关键作用。
