Acute Modulation of Left Ventricular Control by Selective Intracardiac Sympathetic Denervation.

ABSTRACT

BACKGROUND: The sympathetic nervous system plays an integral role in cardiac physiology. Nerve fibers innervating the left ventricle are amenable to transvenous catheter stimulation along the coronary sinus (CS). OBJECTIVES: The aim of the present study was to modulate left ventricular control by selective intracardiac sympathetic denervation. METHODS: First, the impact of epicardial CS ablation on cardiac electrophysiology was studied in a Langendorff model of decentralized murine hearts (n = 10 each, ablation and control groups). Second, the impact of transvenous, anatomically driven axotomy by catheter-based radiofrequency ablation via the CS was evaluated in healthy sheep (n = 8) before and during stellate ganglion stimulation. RESULTS: CS ablation prolonged epicardial ventricular refractory period without (41.8 ± 8.4 ms vs 53.0 ± 13.5 ms; P = 0.049) and with ß1-2-adrenergic receptor blockade (47.8 ± 7.8 ms vs 73.1 ± 13.2 ms; P < 0.001) in mice. Supported by neuromorphological studies illustrating a circumferential CS neural network, intracardiac axotomy by catheter ablation via the CS in healthy sheep diminished the blood pressure increase during stellate ganglion stimulation (Δ systolic blood pressure 21.9 ± 10.9 mm Hg vs 10.5 ± 12.0 mm Hg; P = 0.023; Δ diastolic blood pressure 9.0 ± 5.5 mm Hg vs 3.0 ± 3.5 mm Hg; P = 0.039). CONCLUSIONS: Transvenous, anatomically driven axotomy targeting nerve fibers along the CS enables acute modulation of left ventricular control by selective intracardiac sympathetic denervation.