Isolated Phrenic and Vagus Nerve Stimulation and Conduction Suppression Induced by Electroporation Pulses.

BACKGROUND

Pulsed field ablation (PFA) is a novel non-thermal ablation modality with high myocardial selectivity. However, stimulation and transient dysfunction of adjacent neural structures remain important off-target effects.

OBJECTIVE

To define pulse-parameter effects on excitation, conduction suppression and recovery of phrenic and vagus nerves exposed to single biphasic electroporation pulses.

METHODS

Ex vivo swine phrenic and vagus nerves were studied using a multi-electrode chamber enabling four-channel compound action potential (CAP) recordings. Pulse amplitude, pulse width (0.5-10 μs), and interphase delay (0.5-1000 μs) were systematically varied. Stimulation thresholds and conduction suppression were quantified, and recovery was assessed over time. An in silico model of the phrenic nerve was developed to estimate electric field distribution and support mechanistic interpretation.

RESULTS

Stimulation thresholds increased with decreasing pulse width and interphase delay. Unmyelinated fibers required 6.8-8.3-fold higher voltages than myelinated fibers. Conduction suppression was strongly dependent on pulse parameters, with longer pulse widths and higher amplitudes producing greater conduction suppression. High-amplitude pulses induced complete but reversible conduction suppression, with CAP recovery exceeding 80% within 30 minutes. Modeling showed elevated electric field gradients near the electrodes and predicted particularly high electric-field magnitudes in the perineurium, suggesting that this structure may be affected early during pulse delivery.

CONCLUSION

Single PFA pulses induced both nerve excitation and reversible conduction suppression in isolated porcine phrenic and vagus nerves in a parameter-dependent manner. These findings provide mechanistic insight into PFA-related neural effects and suggest that stimulation of nearby autonomic nerves could potentially contribute to clinical observations such as bradycardia and coronary vasospasm. Quantitative translation will require clinically representative catheter geometries and complete pulse trains.