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在心脏和神经元细胞的体外悬浮模型中建立不可逆电穿孔电场电位阈值

Establishing Irreversible Electroporation Electric Field Potential Threshold in A Suspension In Vitro Model for Cardiac and Neuronal Cells.

作者信息

Avazzadeh Sahar, O'Brien Barry, Coffey Ken, O'Halloran Martin, Keane David, Quinlan Leo R

机构信息

Physiology and Cellular Physiology Research Laboratory, School of Medicine, Human Biology Building, National University of Ireland, H91 TK33 Galway, Ireland.

AtriAN Medical Limited, Unit 204, NUIG Business Innovation Centre, Upper Newcastle, H91 TK33 Galway, Ireland.

出版信息

J Clin Med. 2021 Nov 22;10(22):5443. doi: 10.3390/jcm10225443.

Abstract

AIMS

Irreversible electroporation is an ablation technique being adapted for the treatment of atrial fibrillation. Currently, there are many differences reported in the in vitro and pre-clinical literature for the effective voltage threshold for ablation. The aim of this study is a direct comparison of different cell types within the cardiovascular system and identification of optimal voltage thresholds for selective cell ablation.

METHODS

Monophasic voltage pulses were delivered in a cuvette suspension model. Cell viability and live-dead measurements of three different neuronal lines, cardiomyocytes, and cardiac fibroblasts were assessed under different voltage conditions. The immediate effects of voltage and the evolution of cell death was measured at three different time points post ablation.

RESULTS

All neuronal and atrial cardiomyocyte lines showed cell viability of less than 20% at an electric field of 1000 V/cm when at least 30 pulses were applied with no significant difference amongst them. In contrast, cardiac fibroblasts showed an optimal threshold at 1250 V/cm with a minimum of 50 pulses. Cell death overtime showed an immediate or delayed cell death with a proportion of cell membranes re-sealing after three hours but no significant difference was observed between treatments after 24 h.

CONCLUSIONS

The present data suggest that understanding the optimal threshold of irreversible electroporation is vital for achieving a safe ablation modality without any side-effect in nearby cells. Moreover, the evolution of cell death post electroporation is key to obtaining a full understanding of the effects of IRE and selection of an optimal ablation threshold.

摘要

目的

不可逆电穿孔是一种正在被应用于治疗心房颤动的消融技术。目前,体外和临床前文献报道的消融有效电压阈值存在许多差异。本研究的目的是直接比较心血管系统内不同细胞类型,并确定选择性细胞消融的最佳电压阈值。

方法

在比色皿悬浮模型中施加单相电压脉冲。在不同电压条件下评估三种不同神经元系、心肌细胞和心脏成纤维细胞的细胞活力及活死检测。在消融后三个不同时间点测量电压的即时效应和细胞死亡的演变。

结果

当施加至少30个脉冲时,所有神经元系和心房心肌细胞系在1000V/cm电场下的细胞活力均低于20%,它们之间无显著差异。相比之下,心脏成纤维细胞在1250V/cm时显示出最佳阈值,最少需要50个脉冲。随着时间推移,细胞死亡表现为即时或延迟性细胞死亡,三小时后有一部分细胞膜重新封闭,但24小时后各处理组之间未观察到显著差异。

结论

目前的数据表明,了解不可逆电穿孔的最佳阈值对于实现一种安全的消融方式至关重要,这种方式不会对附近细胞产生任何副作用。此外,电穿孔后细胞死亡的演变是全面了解不可逆电穿孔效应和选择最佳消融阈值的关键。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bb1/8622402/3da2c88d0b38/jcm-10-05443-g001.jpg

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