Technical safety and efficacy of PFA catheter electrode for airway ablation in a rat model of COPD

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction. While current pharmacotherapies provide symptomatic relief, they fail to alter disease progression. Pulsed field ablation (PFA) has emerged as a promising non-thermal technology capable of inducing selective cell death and achieving long-term symptom relief in COPD. However, its clinical translation remains hindered by unclear mechanistic foundations and the lack of specialized preclinical devices necessary for detailed mechanistic studies. We developed a novel PFA catheter specifically designed for rat airways, featuring a platinum-iridium electrode ring (inner diameter: 1.95 mm) integrated with a dual-lumen PVC tube (outer diameter: 1.80 mm) to enable continuous ventilation during ablation. Finite element modeling was employed to systematically evaluate electric field distributions and thermal effects across voltage parameters. Safety was assessed in healthy Sprague-Dawley rats through continuous monitoring of hemodynamic responses, respiratory parameters, and tissue temperature changes. Therapeutic efficacy was evaluated in a cigarette smoke and Lipopolysaccharide-induced COPD model using histopathological analysis, pulmonary function tests, and arterial blood gas measurements at postoperative days 3 and 28. Numerical simulations demonstrated that increasing voltage (100–500 V) and pulse number proportionally expanded both the effective electric field distribution and ablation depth in airway walls, with no thermal injury observed within this range. In vivo validation confirmed that parameters of 200–300 V with 60–90 pulses achieved effective mucosal ablation, inducing epithelial necrosis and sloughing while preserving submucosal and cartilaginous structures without transmural damage. Vital signs monitoring revealed transient, self-resolving arrhythmias and hypotension. In COPD models, PFA treatment significantly reduced goblet cell hyperplasia and inflammation, restored normal epithelial architecture, and improved both pulmonary function and gas exchange. This study demonstrates that an easily fabricated PFA catheter can achieve complete epithelial ablation without transmural or thermal injury using optimized parameters. The procedure produced significant therapeutic improvement through reduction of goblet cell hyperplasia and restoration of pulmonary function, providing a validated platform for further mechanistic exploration and advancing PFA as a precise, non-thermal therapy for COPD. A novel, easily fabricated pulsed field ablation (PFA) catheter with integrated ventilation was developed, enabling safe and effective airway ablation in small animal models. PFA produced a non-thermal, tissue-selective ablation effect that preserved extracellular matrix integrity, with no evidence of transmural injury even in cartilage-rich airway regions, as supported by both simulations and in vivo validation. The fabricated PFA catheter demonstrated a favorable safety profile and robust efficacy in reversing goblet cell hyperplasia and improving pulmonary function in a COPD rat model, providing a solid foundation for further mechanistic and translational studies.