Low-level tragus stimulation improves autoantibody- induced hyperadrenergic postural tachycardia syndrome in rabbits

BACKGROUND Recent studies have demonstrated that antiadre-nergic autoantibodies are involved in the pathophysiology of postural orthostatic tachycardia syndrome (POTS).OBJECTIVE The purpose of this study was to test the hypothesis that transcutaneous low-level tragus stimulation (LLTS) ameliorates autoantibody-induced autonomic dysfunction and inflammation in a rabbit model of autoimmune POTS.METHODS Six New Zealand white rabbits were co-immunized with peptides from the a1-adrenergic and b1-adrenergic receptors to produce sympathomimetic antibodies. The tilt test was performed on conscious rabbits before immunization, 6 weeks after immuniza-tion, and 10 weeks after immunization with 4-week daily LLTS treat-ment. Each rabbit served as its own control.RESULTS An enhanced postural heart rate increase in the absence of significant change in blood pressure was observed in immunized rabbits, confirming our previous report. Power spectral analysis of heart rate variability during the tilt test showed a predominance of sympathetic over parasympathetic activity in immunized rabbits as reflected by markedly increased low-frequency power, decreased high-frequency power, and increased low-to-high-frequency ratio. Serum inflammatory cytokines were also significantly increased in immunized rabbits. LLTS suppressed the postural tachycardia, improved the sympathovagal balance with increased acetylcholine secretion, and attenuated the inflammatory cytokine expression. Antibody production and activity were confirmed with in vitro assays, and no antibody suppression by LLTS was found in this short-term study.CONCLUSION LLTS improves cardiac autonomic imbalance and inflammation in a rabbit model of autoantibody-induced hyperadre-nergic POTS, suggesting that LLTS may be used as a novel neuromo-dulation therapy for POTS.