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用于在Langendorff灌注兔心脏中进行心律失常二维和三维光学与电标测的集成平台。

An integrated platform for 2-D and 3-D optical and electrical mapping of arrhythmias in Langendorff-perfused rabbit hearts.

作者信息

Siles Jimena, Silva Vinícius, Neves Tainan, Sandoval Italo, Quadros Angélica, Weber Giovanni, Barquero Óscar, Uzelac Ilija, Salinet João

机构信息

HEartLab, Federal University of ABC, São Paulo, Brazil.

Graduate Program in Biotechnoscience, Federal University of ABC, São Paulo, Brazil.

出版信息

J Physiol. 2025 Jun 25. doi: 10.1113/JP287815.

DOI:10.1113/JP287815
PMID:40560823
Abstract

Electrophysiological mapping is essential for understanding these mechanisms and guiding therapeutic treatments. However, approaches such as invasive electrical mapping, body surface mapping and electrocardiographic imaging face challenges, including low spatial resolution, far-field interference and signal processing limitations. By contrast, panoramic optical mapping, using fluorescent dyes, offers high spatial resolution and allows direct measurement of cellular action potential ex situ. Can the integration of panoramic optical mapping with electrical mapping overcome the limitations of the above-cited techniques and provide deeper insights into arrhythmic mechanisms? To investigate this, we developed an experimental setup that combines 3-D panoramic optical mapping with multi-electrode epicardial electrical mapping and non-invasive electrical mapping (torso-tank setup) for electrocardiographic imaging in Langendorff-perfused rabbit hearts. Our results confirm the feasibility of using simultaneous optical and electrical mapping under sinus rhythm, as well as in atrial and ventricular arrhythmias, using time, frequency and phase analyses. During sinus rhythm and ventricular tachycardia, wavefront propagation showed concordance between modalities, where diverges are observed for atrial arrhythmias. Dominant frequency analysis could recover the frequency of activation better than the inverse of cycle length, and outcomes from all mapping modalities agreed. Reconstructed electrograms presented a good similarity compared to electrograms. By correlating optical and electrical mapping, clinically relevant arrhythmia markers and targets for ablation, from invasive and non-invasive mapping can be better understood and localised. This platform could also serve as a test bed for studying drug effects, connecting changes from cellular action potential levels to whole-heart electrophysiology. KEY POINTS: Cardiac arrhythmias are still a significant challenge in electrophysiology, with advancements in experimental and clinical research improving our understanding of mechanisms and target for ablation. Current electrical mapping technology, both invasive and non-invasive, is used in science and by commercial systems to identify arrhythmic episodes and mechanisms, but has several limitations mimicking the true electrophysiology behaviour. Optical mapping uses fluorescent dyes to measure transmembrane action potentials with high spatial resolution. When combined with electrical mapping, it can enhance cardiac arrhythmia studies and mapping technologies. A novel 3-D platform that integrates panoramic and electrical mapping techniques (epicardium, non-invasive torso-tank and electrocardiographic imaging) is presented and validated in isolated rabbit hearts, highlighting that the mapping strategies do not always agree, helping to further improve commercial systems.

摘要

电生理标测对于理解这些机制和指导治疗至关重要。然而,诸如侵入性电标测、体表标测和心电图成像等方法面临挑战,包括空间分辨率低、远场干扰和信号处理限制。相比之下,使用荧光染料的全景光学标测具有高空间分辨率,并允许在体外直接测量细胞动作电位。全景光学标测与电标测的整合能否克服上述技术的局限性,并更深入地洞察心律失常机制?为了研究这一问题,我们开发了一种实验装置,将三维全景光学标测与多电极心外膜电标测和非侵入性电标测(躯干槽装置)相结合,用于在Langendorff灌注兔心脏中进行心电图成像。我们的结果证实了在窦性心律以及房性和室性心律失常情况下,使用时间、频率和相位分析同时进行光学和电标测的可行性。在窦性心律和室性心动过速期间,波前传播在不同模式之间显示出一致性,而在房性心律失常中观察到差异。主导频率分析比心动周期长度的倒数能更好地恢复激活频率,并且所有标测模式的结果一致。重建的心电图与实际心电图具有良好的相似性。通过关联光学和电标测,可以更好地理解和定位来自侵入性和非侵入性标测的临床相关心律失常标志物和消融靶点。该平台还可作为研究药物作用的试验台,将细胞动作电位水平的变化与全心电生理学联系起来。要点:心律失常在电生理学中仍然是一个重大挑战,实验和临床研究的进展增进了我们对机制和消融靶点的理解。当前的电标测技术,无论是侵入性还是非侵入性的,都被科学研究和商业系统用于识别心律失常发作和机制,但在模拟真实电生理行为方面存在一些局限性。光学标测使用荧光染料以高空间分辨率测量跨膜动作电位。当与电标测结合时,它可以增强对心律失常的研究和标测技术。本文介绍了一种整合全景和电标测技术(心外膜、非侵入性躯干槽和心电图成像)的新型三维平台,并在离体兔心脏中进行了验证,强调标测策略并不总是一致,这有助于进一步改进商业系统。

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