Baena-Montes Jara M, O'Halloran Tony, Clarke Cormac, Donaghey Kevin, Dunne Eoghan, O'Halloran Martin, Quinlan Leo R
Cellular Physiology Research Laboratory, CÚRAM SFI Centre for Research in Medical Devices, School of Medicine, Human Biology Building, National University of Ireland (NUI), H91 W5P7 Galway, Ireland.
School of Medicine, National University of Ireland (NUI), H91 W5P7 Galway, Ireland.
J Cardiovasc Dev Dis. 2022 Jul 28;9(8):240. doi: 10.3390/jcdd9080240.
Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy sources. However, more tissue and cell-specific evidence is required to demonstrate the selective threshold parameters for human cells. The aim here is to determine the optimal ablation threshold parameters related to lesion size for human cardiomyocytes in 2D culture. Conventional biphasic pulses of different field strengths and on-times were delivered in a monolayer culture system of human AC16 cardiomyocytes. The dynamics of cell death and lesion dimensions were examined at different time points. Human cardiomyocytes are susceptible to significant electroporation and cell death at a field strength of 750 V/cm or higher with 100 μs pulses. Increasing the IRE on-time from 3 ms to 60 ms reduces the effective field threshold to 250 V/cm. Using very short pulses of 2 μs and 5 μs also causes significant cell death, but only at fields higher than 1000 V/cm. A longer on-time results in more cell death and induced greater lesion area in 2D models. In addition, different forms of cell death are predicted based on the evolution of cell death over time. This study presents important findings on the ability of different IRE parameters to induce human cardiomyocyte cell death. Lesion size can be tuned by appropriate choice of IRE parameters and cardiomyocytes display an upregulation of delayed cell death 24 h after electroporation, which is an important consideration for clinical practice.
不可逆电穿孔（IRE）心脏消融术正迅速成为心房颤动治疗的首选方式。虽然尚未优化，但IRE有潜力显著限制附带损伤，并改善与其他能量源相关的细胞特异性靶向。然而，需要更多组织和细胞特异性证据来证明人类细胞的选择性阈值参数。本文旨在确定二维培养中人类心肌细胞与损伤大小相关的最佳消融阈值参数。在人类AC16心肌细胞的单层培养系统中施加不同场强和脉冲持续时间的传统双相脉冲。在不同时间点检查细胞死亡动态和损伤尺寸。人类心肌细胞在750V/cm或更高场强及100μs脉冲下易发生显著电穿孔和细胞死亡。将IRE脉冲持续时间从3ms增加到60ms可将有效场阈值降低至250V/cm。使用2μs和5μs的极短脉冲也会导致显著细胞死亡，但仅在高于1000V/cm的场强下。在二维模型中，较长的脉冲持续时间会导致更多细胞死亡并诱导更大的损伤面积。此外，根据细胞死亡随时间的演变预测了不同形式的细胞死亡。本研究提出了关于不同IRE参数诱导人类心肌细胞死亡能力的重要发现。通过适当选择IRE参数可调节损伤大小，并且心肌细胞在电穿孔后24小时显示延迟细胞死亡上调，这是临床实践中的一个重要考虑因素。
