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Catheter Stimulation of Cardiac Parasympathetic Nerves in Humans: A Novel Approach to the Cardiac Autonomic Nervous System

Background—Cardiac parasympathetic nerves run alongside the superior vena cava (SVC) and accumulate particularly epicardially adjacent to the orifice of the coronary sinus (CS). In animals, these nerves can be electrically stimulated inside the SVC or CS, which results in negative chronotropic/dromotropic effects and negative inotropic effects in the atria but not the ventricles. Parasympathetic nerve stimulation (PS) with 20 Hz in the CS, however, also excites the atria, thereby inducing atrial fibrillation. The present study overcomes this limitation by applying high-frequency nerve stimuli within the atrial refractory period. Using this technique, we investigated for the first time whether neurophysiological effects similar to those in animals can be obtained in humans. Methods and Results—In 25 patients, parasympathetic nerves were stimulated via a multipolar electrode catheter placed in the SVC (stimulation with 20 Hz; n=14) or CS (pulsed 200-Hz stimuli; n=11). A significant sinus rate decrease and prolongation of the antegrade Wenckebach period was achieved during PS in the SVC. During PS in the CS, a graded-response prolongation of the antegrade Wenckebach interval was observed with increasing PS voltage until third-degree AV block occurred in 8 of 11 patients. The negative chronotropic/dromotropic effects started and terminated immediately after the onset and termination of PS, respectively. Atropine abolished these effects (n=11). Conclusions—Human parasympathetic efferent nerve stimulation induces reversible negative chronotropic and dromotropic effects. PS may serve as an adjunctive tool for the diagnosis/treatment of supraventricular tachycardias and may be beneficial for ventricular rate slowing during tachycardic atrial fibrillation in patients with congestive heart failure.