Key result
Increasing irreversible electroporation on-time reduces the human cardiomyocyte death threshold to 250 V/cm.
Why the study?
Irreversible electroporation is not yet optimized for AF ablation, and more cell-specific evidence is required to demonstrate selective threshold parameters for human cardiomyocytes.
In vitro human cardiomyocyte models demonstrate that irreversible electroporation lesion size and cell death thresholds can be tuned by adjusting field strength and on-time, with delayed cell death observed at 24 hours.
May guide IRE parameter selection in cardiomyocyte models; hypothesis-generating for clinical ablation translation.
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.
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Baena-Montes et al. (2022) studied Atrial fibrillation (cardiomyocyte ablation). Irreversible electroporation (IRE) was evaluated on Dynamics of cell death and lesion dimensions. Irreversible electroporation induced significant human cardiomyocyte cell death at field strengths ≥750 V/cm with 100 μs pulses, and increasing on-time to 60 ms reduced the threshold to 250 V/cm.
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