Stimulus frequency differences in respiratory inhibition is negligible to optimize vagal nerve stimulation (VNS) for heart failure

Although VNS benefits for heart failure, up titrations are limited in 72 % of human subject because of respiratory side effects. Since vagal nerves are connected to the respiratory center in brainstem, VNS is possible to change respiratory rhythms. In this study, we investigated how the frequency differences in VNS impact on respiration. In Sprague-Dawley rats (N=4), we changed the stimulus frequencies (5, 10, 20, and 50 Hz) and amplitude of VNS (0-8 V). In low frequencies (5 and 10 Hz), VNS slightly inhibited respiration with stimulus amplitudes. Maximum inhibition of minute ventilation was -18.4 ± 0.1 % in 5 Hz and -47.1 ± 2.7 % in 10 Hz. While in high frequencies (20 and 50 Hz), VNS induced apnea above 2-4 V. In conclusion, high stimulus frequency induced remarkable respiratory inhibition and apnea. It is negligible effect to titrate VNS.