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.

Highlights

  • The optimal threshold was defined as the minimum electric field and pulse number that resulted in an 80% reduction in cell viability

  • There was no significant difference in cell viability between neuronal cell lines at this voltage level (Figure 2G,H)

  • There was a significant difference in lethal ablation threshold when comparing cardiomyocytes and cardiac fibroblasts, with cardiomyocytes showing significantly higher cell death (Figure 3F–H)

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Summary

Introduction

The therapeutic value of cardiac ablation has been transformed through iterative technology development, leading to enhanced treatment safety and efficacy for atrial fibrillation (AF), atrial flutter, and ventricular arrhythmias. AF is the most common form of cardiac arrhythmia widely associated with increased age, though occurs in young adults and adolescent [1]. AF is usually precipitated by many underlying factors such as hypertension, hyperthyroidism [2], alcohol consumption, smoking [3], and channelopathies [4]. Cardiac ablation aims to destroy arrhythmogenic tissue, creating a permanent lesion

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