Closed-loop bioelectronic block of stellate ganglia reduces neurotransmitter release and improves recovery following programmed ventricular pacing.

Introduction: The autonomic nervous system governs cardiac function through a finely-balanced interplay of sympathetic and parasympathetic activity. Following myocardial infarction chronic sympathetic hyperactivation destabilizes this balance, increases arrhythmia formation, and exacerbates cardiac dysfunction. Current treatments such as pharmaceuticals, surgical sympathectomies, and ablations, are either systemic, irreversible, or non-titratable, underscoring the need for targeted, adaptive interventions. Methods: Here we show that a closed-loop fuzzy logic controller, using real-time norepinephrine (NE) measurements via fast-scanning cyclic voltammetry as a feedback signal, can drive direct current (DC) electrical nerve block of the paravertebral sympathetic chain to achieve graded, on-demand reductions in cardiac NE release in both healthy (n = 6) and chronically infarcted (n = 5) male Yorkshire pigs. Results: Controller-directed block produced significant reductions in peak and sustained NE release at target setpoints of 33% and 66% in both animal models, with corresponding improvements in left ventricular systolic pressure recovery post-pacing. Discussion: These findings establish bioelectronic closed-loop sympathetic nerve block as a viable, reversible alternative to surgical sympathectomy. By delivering an electrical block to create an "on-demand sympathectomy", refractory ventricular arrhythmia and post-infarction sympathetic dysregulation can be managed in real-time, side effects can be eliminated, providing the ultimate patient-specific treatment.