Vagal nerve stimulation activates vagal afferent fibers that reduce cardiac efferent parasympathetic effects

Abstract

Vagal nerve stimulation (VNS) has been shown to have antiarrhythmic effects, but many of these benefits were demonstrated in the setting of vagal nerve decentralization. The purpose of this study was to evaluate the role of afferent fiber activation during VNS on efferent control of cardiac hemodynamic and electrophysiological parameters. In 37 pigs a 56-electrode sock was placed over the ventricles to record local activation recovery intervals (ARIs), a surrogate of action potential duration. In 12 of 37 animals atropine was given systemically. Right and left VNS were performed under six conditions: both vagal trunks intact (n = 25), ipsilateral right (n = 11), ipsilateral left (n = 14), contralateral right (n = 7), contralateral left (n = 10), and bilateral (n = 25) vagal nerve transection (VNTx). Unilateral VNTx significantly affected heart rate, PR interval, Tau, and global ARIs. Right VNS after ipsilateral VNTx had augmented effects on hemodynamic parameters and increase in ARI, while subsequent bilateral VNTx did not significantly modify this effect (%change in ARI in intact condition 2.2 ± 0.9% vs. ipsilateral VNTx 5.3 ± 1.7% and bilateral VNTx 5.3 ± 0.8%, P < 0.05). Left VNS after left VNTx tended to increase its effects on hemodynamics and ARI response (P = 0.07), but only after bilateral VNTx did these changes reach significance (intact 1.1 ± 0.5% vs. ipsilateral VNTx 3.6 ± 0.7% and bilateral VNTx 6.6 ± 1.6%, P < 0.05 vs. intact). Contralateral VNTx did not modify VNS response. The effect of atropine on ventricular ARI was similar to bilateral VNTx. We found that VNS activates afferent fibers in the ipsilateral vagal nerve, which reflexively inhibit cardiac parasympathetic efferent electrophysiological and hemodynamic effects.

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction

“…Given the infarct location, it's also possible that afferent signaling to the brainstem -especially the left nucleus tractus solitarius, which provides input to the left nucleus ambiguus and left dorsal motor nucleus of the vagus -is altered and leads to a reduction of parasympathetic drive through the left vagal trunk (25)(26)(27). However, both vagal trunks are needed to maintain normal parasympathetic tone, and transection of one trunk can have significant electrophysiological consequences in porcine and canine hearts (28,29). Therefore, decreased parasympathetic outflow through the left vagus can have profound effects on the ventricular myocardium, particularly in the infarcted region.…”

“…Arterial blood gas levels were measured hourly. After completion of surgical exposure, anesthetics were switched from isoflurane to α-chloralose (Sigma-Aldrich; 50 mg/kg initial bolus, then 20-35 mg/kg/hr) (14,28,48) for in vivo neuronal recordings, followed by stabilization period of 1 hour. Animals were euthanized by an overdose of i.v.…”

Cardiac neuroanatomy - Imaging nerves to define functional control

“…Adapted from Yamakawa et al . 79 B, ARI maps in control porcine hearts at baseline (BL) and during right (RSG), left (LSG) and bilateral (BSG) stellate ganglion stimulation. Myocardial regions are displayed in the BL control map.…”

“…Studies have evaluated how autonomic nerve stimulation affects mechanical and electrocardiographic parameters of the heart (Figure 7). 76–79 Norris et al placed strain gauges on the epicardium and electrically stimulated sympathetic nerves in canines to measure regional inotropy to determine gross functional innervation patterns. 80,81 The positive and negative chronotropic effect of sympathetic and parasympathetic simulation on SA node activity, respectively, were originally described in studies employing nerve stimulation while monitoring heart rate.…”

Cardiac Innervation and the Autonomic Nervous System in Sudden Cardiac Death

“…As mentioned above, the vagosympathetic trunk contains both parasympathetic and sympathetic as well as afferent and efferent nerves. Different stimulation parameters can differentially engage these fibers 118 and the effects of VNS is significantly increased when the vagosympathetic trunk is transected in animal studies, 119,120 demonstrating the powerful effects of afferent fiber activation on efferent effects. In addition, a case of a patient experiencing an increase in ventricular arrhythmias after VNS has been reported.…”