Catheter Ablation -> Atrial Fibrillation & Atrial Flutter: -> Ablation Techniques
D-PO02 - Poster Session II (ID 47)
Poster
D-PO02-139 - Human Cell Models Of Unipolar Electroporation Injury Across Cell Type (ID 1028)
Abstract
Background: Phrenic nerve and esophageal damage are side effects of PVI which constrain energy levels for lesion formation. We previously developed a rat cell model to study the effects of electroporation (ELP) injury on various cell types and demonstrated cardiac selectivity with bipolar energy delivery. Here we develop a human cell model and use the model to test unipolar energy delivery.
Objective: To develop a human model of ELP injury and use it to determine how cell type impacts the ELP efficacy.
Methods: Human induced pluripotent stem cell derived cardiomyocyte (CM) monolayers were voltage-mapped to evaluate conduction path before and after ELP to determine conduction block (CB) thresholds. Propidium iodide (PI) staining was used to measure shock induced membrane damage and cell death in both CMs and human esophageal smooth muscle cells (SMCs) at the CB threshold. Biphasic shocks (10 ms) were delivered from a unipolar electrode and distant return with the first phase being either anodal or cathodal.
Results: CB thresholds were approximately 50 V for both anodal and cathodal shocks (Fig. 1A). At 50 V, CMs were significantly more susceptible to the shocks than SMCs (~60 % cell death vs ~5 %, Fig. 1B). CMs were more easily killed than SMCs even when the SMC voltage was raised to 130 V.
Conclusion: We developed a human cell model that showed cell specific damage with ELP but no difference between anodal and cathodal (leading edge) shocks. ELP selectivity was demonstrated without the confounding influences present in three dimensional preclinical and clinical studies. This is an excellent platform for studying efficacy differences between the potential ELP waveforms being explored today.
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Objective: To develop a human model of ELP injury and use it to determine how cell type impacts the ELP efficacy.
Methods: Human induced pluripotent stem cell derived cardiomyocyte (CM) monolayers were voltage-mapped to evaluate conduction path before and after ELP to determine conduction block (CB) thresholds. Propidium iodide (PI) staining was used to measure shock induced membrane damage and cell death in both CMs and human esophageal smooth muscle cells (SMCs) at the CB threshold. Biphasic shocks (10 ms) were delivered from a unipolar electrode and distant return with the first phase being either anodal or cathodal.
Results: CB thresholds were approximately 50 V for both anodal and cathodal shocks (Fig. 1A). At 50 V, CMs were significantly more susceptible to the shocks than SMCs (~60 % cell death vs ~5 %, Fig. 1B). CMs were more easily killed than SMCs even when the SMC voltage was raised to 130 V.
Conclusion: We developed a human cell model that showed cell specific damage with ELP but no difference between anodal and cathodal (leading edge) shocks. ELP selectivity was demonstrated without the confounding influences present in three dimensional preclinical and clinical studies. This is an excellent platform for studying efficacy differences between the potential ELP waveforms being explored today.
