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.
Recently, non-thermal pulsed-fieldablation using electroporation has generated a lot of interest as a potential treatment for Atrial Fibrillation. The electrical properties, and specially the conductivity of cardiac tissues, are used in the in treatment planning of non-thermal pulsed field ablation. However, there is no standard approach to measure the conductivity, particularly for the left atrial appendage (LAA). Electrical conductivity characterization studies, focusing on cardiac tissues, have used different probe typologies with different electrodes sizes. Furthermore, no study has investigated the effect of the probe design on the acquired conductivity. In this study, common leading probe typologies with different electrode size are compared in terms of accuracy and measurement repeatability. Using liquid phantoms, differences in term of measurement accuracy and repeatability are observed between the probe designs which suggests that the measurement probe design influences the data acquisition quality.Based on these results, a custom probe design is proposed suitable for the characterization of the conductivity of the LAA. The probe is tested using ten ex vivo bovine tissue samples between 0.1 Hz and 100 kHz. The mean conductivity of the LAA acquired from the ten samples is 2.5 mS/cm with a standard deviation of 0.24 mS/cm which is in line with conductivity of cardiac tissues in the literature. The conductivity values of the left atrial appendage may be useful in electroporation treatment planning, furthermore this study suggests that adapting the probe design to the tissue under study can be important.
The electrical properties of many biological tissues are freely available from the INRC and the IT’IS databases. However, particularly in lower frequency ranges, few studies have investigated the optimal measurement protocol or the key confounders that need to be controlled, monitored, and reported. However, preliminary work suggests that the contact force of the measurement probe on the tissue sample can affect the measurements. The aim of this paper is to investigate the conductivity change due to the probe contact force in detail. Twenty ex vivo bovine heart samples are used, and conductivity measurements are taken in the Left Atrial Appendage, a common target for medical device developments. The conductivity measurements reported in this work (between 0.14 S/m and 0.24 S/m) align with the literature. The average conductivity is observed to change by −21% as the contact force increases from 2 N to 10 N. In contrast, in conditions where the fluid concentration in the measurement area is expected to be lower, very small changes are observed (less than 2.5%). These results suggest that the LAA conductivity is affected by the contact force due to the fluid concentration in the tissue. This work suggests that contact force should be controlled for in all future experiments.
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