Mechanisms and time course of cell death in pulsed field ablation
Abstract
Pulsed field ablation (PFA) is increasingly used for atrial fibrillation, but the mechanisms of PFA-induced cell death remain incompletely understood. This study aimed to elucidate the early mechanisms and temporal dynamics of cell death induced by PFA as acute indicators of ablation effectiveness in pre-clinical models. Epicardial left ventricular ablations were performed using the AblaView® System, with lesions created at predefined locations. Hearts were harvested for histopathological and immunohistochemical analysis at 10, 40, and 100 minutes, as well as at 1-month post-ablation, while a separate survival cohort was also examined at 1 month. Structural damage and lesion borders were assessed using routine histology and desmin staining, and regulated cell death pathways, inflammation, and metabolic stress were evaluated via immunohistochemistry. PFA produced lesions with comparable biophysical parameters across all time points. Within minutes, structural markers revealed loss of cardiomyocyte striation, increased intercellular spacing, and disappearance of myocardial anisotropy. RIPK3 and Gasdermin increased significantly over time (both p=0.01), indicating activation of necroptotic and pyroptotic pathways, while caspase-8 showed transient elevation consistent with extrinsic apoptotic signaling. Myeloperoxidase staining increased over time (p<0.05), reflecting neutrophil-driven inflammation, and GLUT1 inhibition at 100 minutes suggested hypoxia and metabolic stress. At 1-month, ablated regions were replaced by fibrotic scar tissue. Overall, PFA induces multiple regulated cell death pathways—including apoptosis, necroptosis, and pyroptosis—alongside inflammation and hypoxia-associated stress, ultimately leading to chronic scar formation; these acute markers may support the development of new tools to better characterize PFA lesions and assess ablation effectiveness.
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BibTeX
@article{herranz2026mechanisms,
title = {{Mechanisms and time course of cell death in pulsed field ablation}},
author = {David Herranz and Eduardo Caleiras and Quim Castellví and Christian Jay Vera and Fernando Peláez and Antoni Ivorra and Carlota Largo Aramburu and Christophe Bailleul and Raphaël P Martins and Atul Verma},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-70530-5},
url = {https://hal.science/hal-05785918v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mechanisms and time course of cell death in pulsed field ablation
AU - David Herranz
AU - Eduardo Caleiras
AU - Quim Castellví
AU - Christian Jay Vera
AU - Fernando Peláez
AU - Antoni Ivorra
AU - Carlota Largo Aramburu
AU - Christophe Bailleul
AU - Raphaël P Martins
AU - Atul Verma
PY - 2026
DA - 2026/10/08
JO - Scientific Reports
DO - 10.1038/s41598-026-70530-5
UR - https://hal.science/hal-05785918v1
AB - Pulsed field ablation (PFA) is increasingly used for atrial fibrillation, but the mechanisms of PFA-induced cell death remain incompletely understood. This study aimed to elucidate the early mechanisms and temporal dynamics of cell death induced by PFA as acute indicators of ablation effectiveness in pre-clinical models. Epicardial left ventricular ablations were performed using the AblaView® System, with lesions created at predefined locations. Hearts were harvested for histopathological and immunohistochemical analysis at 10, 40, and 100 minutes, as well as at 1-month post-ablation, while a separate survival cohort was also examined at 1 month. Structural damage and lesion borders were assessed using routine histology and desmin staining, and regulated cell death pathways, inflammation, and metabolic stress were evaluated via immunohistochemistry. PFA produced lesions with comparable biophysical parameters across all time points. Within minutes, structural markers revealed loss of cardiomyocyte striation, increased intercellular spacing, and disappearance of myocardial anisotropy. RIPK3 and Gasdermin increased significantly over time (both p=0.01), indicating activation of necroptotic and pyroptotic pathways, while caspase-8 showed transient elevation consistent with extrinsic apoptotic signaling. Myeloperoxidase staining increased over time (p<0.05), reflecting neutrophil-driven inflammation, and GLUT1 inhibition at 100 minutes suggested hypoxia and metabolic stress. At 1-month, ablated regions were replaced by fibrotic scar tissue. Overall, PFA induces multiple regulated cell death pathways—including apoptosis, necroptosis, and pyroptosis—alongside inflammation and hypoxia-associated stress, ultimately leading to chronic scar formation; these acute markers may support the development of new tools to better characterize PFA lesions and assess ablation effectiveness.
SN - 2045-2322
ER -