Excitation properties of the right cervical vagus nerve in adult dogs

Abstract

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and depression, and it is currently under investigation for applications in Alzheimer's disease, anxiety, heart failure, and obesity. However, the mechanism(s) by which VNS has its effects are not clear, and the stimulation parameters for obtaining therapeutic outcomes appear highly variable. The purpose of this study was to quantify the excitation properties of the right cervical vagus nerve in adult dogs anesthetized with propofol and fentanyl. Input-output curves of the right cervical vagus nerve compound action potential and laryngeal muscle electromyogram were measured in response to VNS across a range of stimulation parameters: amplitudes of 0.02-50mA, pulsewidths of 10, 50, 100, 200, 300, 500, and 1,000μs, frequencies of 1-2Hz, and train lengths of 20 pulses with 3 different electrode configurations: monopolar cathode, proximal anode/distal cathode, and proximal cathode/distal anode. Electrode configuration and stimulation waveform (monophasic vs. asymmetric charge-balanced biphasic) did not affect the threshold or recruitment of the vagal nerve fibers that were activated. The rheobase currents of A- and B-fibers were 0.4mA and 0.7mA, respectively, and the chronaxie of both components was 180μs. Pulsewidth had little effect on the normalized threshold difference between activation of A- and B-fibers. The results provide insight into the complement of nerve fibers activated by VNS and guidance to clinicians for the selection of optimal stimulation parameters.