Abstract

Introduction: Reduced heart rate variability (HRV) is associated with increased risk of cardiovascular morbidity and mortality. Previous studies have shown that transcutaneous vagus nerve stimulation (tVNS) increases HRV and improves autonomic function, but the effect of variable stimulation parameters on autonomic function remains unclear. Hypothesis: We examined the effect of variable stimulation parameters of tVNS on autonomic function. Methods: Healthy volunteers were recruited for this study. Each participant underwent autonomic function testing consisting of HRV during deep breathing and mental arithmetic stress test (MAST), with and without tVNS. Participants were randomized to 4 groups of different stimulation parameters in a 2x2 fashion (frequency 5Hz and 20Hz; amplitude 1mA below discomfort threshold or 50% below discomfort threshold). tVNS was applied for 5 minutes for each session. HRV was analyzed in a blinded fashion using Kubios software. Results were compared with 2-way ANOVA, adjusted for multiple comparisons. Results: Thirty participants were included (mean age 39±14 years, 70% female). Stimulation amplitude was 26±13 mA and 14±7 mA in the 1mA below and 50% below discomfort threshold groups (p=0.001). There was a greater change in HRV parameters with 20Hz vs. 5Hz stimulation versus baseline during MAST (low frequency: -8.1±2.8%, vs. 1.4±1.8%, p=0.01; high frequency 8.2±3.7% vs. -1.3±1.8%, p=0.03; SD2 of Poincare plot -7.9±2.9 ms vs. 4.2±3.1 ms, p=0.005, respectively; Figure). No differences were observed between the 2 different amplitude groups. Conclusions: Stimulation frequency may influence the acute effect of autonomic modulation on autonomic function parameters. These findings have implications for autonomic modulation study design. Further studies in disease states are warranted.

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