Exploration of Intrafascicular Vagus Nerve Stimulation on Blood Pressure Reduction

doi:10.1007/s12204-024-2767-3

Abstract

Abstract: The vagus nerve plays a pivotal role in regulating blood pressure, making vagus nerve stimulation a promising therapy for refractory hypertension. Nevertheless, most current research on vagus nerve stimulation for hypertension regulation employs rigid electrodes outside the nerve bundle, with limited exploration into the electrical stimulation paradigms. In this study, we employed the carbon nanotube yarn electrode, a flexible electrode, implanted in the left vagus nerve of rats to compare the modulatory effects of duty cycle and pulse width stimulation paradigms. Furthermore, we conducted a quantitative electrical stimulation experiment using the optimized duty cycle paradigm. The result showed that low-frequency stimulation yielded superior blood pressure regulation, whereas high-frequency stimulation resulted in apnea. In conclusion, intrafascicular vagus nerve stimulation with the duty-cycle paradigm demonstrated superior efficacy in reducing blood pressure compared to the pulse-width paradigm, with an optimal duty cycle identified at 20%. These findings offer valuable insights for optimizing vagus nerve stimulation protocols in the treatment of hypertension.

Key words: vagus nerve stimulation, hypertension, intrafascicular electrodes

摘要： 迷走神经在调节血压中起着关键作用，使迷走神经刺激成为治疗难治性高血压的一种很有前景的治疗方法。目前关于迷走神经刺激调节高血压的研究大多采用神经束外的刚性电极，对电刺激范式的探索有限。本研究采用柔性电极碳纳米管纤维电极植入大鼠左侧迷走神经，比较了占空比和脉宽刺激范式对血压的调节作用。此外，使用优化的占空比范式进行了定量电刺激实验。结果表明：低频刺激对血压的调节效果较好，而高频刺激导致呼吸暂停。与脉宽模式相比，束内迷走神经刺激在降低血压方面表现出更好的效果，最佳占空比为20%。这些发现为优化迷走神经刺激治疗高血压的方案提供了有价值的见解。

关键词: 迷走神经刺激，高血压，神经束内电极

CLC Number:

R318

Tian Haoyang, Gu Mingcheng, Li Runhuan, Jin Mingyu, Peng Wei, Sui Xiaohong. Exploration of Intrafascicular Vagus Nerve Stimulation on Blood Pressure Reduction[J]. J Shanghai Jiaotong Univ Sci, 2025, 30(4): 702-708.

References

[1] MILLS K T, STEFANESCU A, HE J. The global epidemiology of hypertension [J]. Nature Reviews Nephrology, 2020, 16(4): 223-237. [2] NAGARAJAN N, JALAL D. Resistant hypertension: Diagnosis and management [J]. Advances in Chronic Kidney Disease, 2019, 26(2): 99-109. [3] BLAZEK O, BAKRIS G L. Novel therapies on the horizon of hypertension management [J]. American Journal of Hypertension, 2023, 36(2): 73-81. [4] KUNZ M, LAUDER L, EWEN S, et al. The current status of devices for the treatment of resistant hypertension [J]. American Journal of Hypertension, 2020, 33(1): 10-18. [5] LOHMEIER T E, HALL J E. Device-based neuromodulation for resistant hypertension therapy [J]. Circulation Research, 2019, 124(7): 1071-1093. [6] OGOYAMA Y, KARIO K. Patient preference and Long-term outcome of renal denervation for resistant hypertension [J]. Hypertension Research: Official Journal of the Japanese Society of Hypertension, 2022, 45(8): 1271-1273. [7] MANCIA G, PARATI G, ZANCHETTI A. Electrical carotid baroreceptor stimulation in resistant hypertension [J]. Hypertension, 2010, 55(3): 607-609. [8] BROWNING K N, VERHEIJDEN S, BOECKXSTAENS G E. The vagus nerve in appetite regulation, mood, and intestinal inflammation [J]. Gastroenterology, 2017, 152(4): 730-744. [9] PAVLOV V A, TRACEY K J. The vagus nerve and the inflammatory reflex: Linking immunity and metabolism [J]. Nature Reviews Endocrinology, 2012, 8(12): 743-754. [10] GUO J Y, LI R H, WANG J J, et al. Blood pressure change in intrafascicular vagal activities [J]. Journal of Shanghai Jiao Tong University (Science), 2021, 26(1): 47-54. [11] ARRANZ J, GUO J Y, YU X, et al. Intrafascicular vagal activity recording and analysis based on carbon nanotube yarn electrodes [J]. Journal of Shanghai Jiao Tong University (Science), 2020, 25(4): 447-452. [12] JALIFE J, MOE G K. Phasic effects of vagal stimulation on pacemaker activity of the isolated sinus node of the young cat [J]. Circulation Research, 1979, 45(5): 595-608. [13] KOWALLIK P, GILMOUR R F, FLEISCHER S, et al. Different vagal modulation of the sinoatrial node and AV node in patients with congestive heart failure [J]. Clinical Science, 1996, 91(Sup.1): 58-61. [14] INOKAITIS H, PAUZIENE N, PAUZA D H. The distribution of sinoatrial nodal cells and their innervation in the pig [J]. Anatomical Record, 2023, 306(9): 2333-2344. [15] MICHAELS D C, SLENTER V A, SALATA J J, et al. A model of dynamic vagus-sinoatrial node interactions [J]. The American Journal of Physiology, 1983, 245(6): H1043-H1053. [16] STAUSS H M, KURIAN A P, ORELLANA J N, et al. Anti-inflammatory effect of noninvasive transcutaneous auricular vagus nerve stimulation and osteopathic manipulative treatment [J]. The FASEB Journal, 2020, 34(S1): 1. [17] DENG J L, LI H L, GUO Y K, et al. Transcutaneous vagus nerve stimulation attenuates autoantibody-mediated cardiovagal dysfunction and inflammation in a rabbit model of postural tachycardia syndrome [J]. Journal of Interventional Cardiac Electrophysiology, 2023, 66(2): 291-300. [18] CAPILUPI M J, KERATH S M, BECKER L B. Vagus nerve stimulation and the cardiovascular system [J]. Cold Spring Harbor Perspectives in Medicine, 2020, 10(2): a034173. [19] PLACHTA D T T, GIERTHMUEHLEN M, COTA O, et al. Blood pressure control with selective vagal nerve stimulation and minimal side effects [J]. Journal of Neural Engineering, 2014, 11(3): 036011. [20] SEVCENCU C, NIELSEN T N, STRUIJK J J. A neural blood pressure marker for bioelectronic medicines for treatment of hypertension [J]. Biosensors and Bioelectronics, 2017, 98: 1-6. [21] ANNONI E M, VAN HELDEN D, GUO Y, et al. Chronic low-level vagus nerve stimulation improves long-term survival in salt-sensitive hypertensive rats [J]. Frontiers in Physiology, 2019, 10: 25. [22] YU X, SU J Y, GUO J Y, et al. Spatiotemporal characteristics of neural activity in tibial nerves with carbon nanotube yarn electrodes [J]. Journal of Neuroscience Methods, 2019, 328: 108450. [23] RIVERA-CASTRO M E, PASTELíN C F, BRAVO-BENíTEZ J, et al. Organization of the subdiaphragmatic vagus nerve and its connection with the celiac plexus and the ovaries in the female rat [J]. Brain Sciences, 2023, 13(7): 1032. [24] KRAHL S E, SENANAYAKE S S, PEKARY A E, et al. Vagus nerve stimulation (VNS) is effective in a rat model of antidepressant action [J]. Journal of Psychiatric Research, 2004, 38(3): 237-240. [25] NOLLER C M, LEVINE Y A, URAKOV T M, et al. Vagus nerve stimulation in rodent models: An overview of technical considerations [J]. Frontiers in Neuroscience, 2019, 13: 911. [26] ALLEN E, PONGPAOPATTANAKUL P, CHAUHAN R A, et al. The effects of vagus nerve stimulation on ventricular electrophysiology and nitric oxide release in the rabbit heart [J]. Frontiers in Physiology, 2022, 13: 867705. [27] STRAUSS I, AGNESI F, ZINNO C, et al. Neural stimulation hardware for the selective intrafascicular modulation of the vagus nerve [J]. IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2023, 31: 4449-4458. [28] MCCALLUM G A, SUI X H, QIU C, et al. Chronic interfacing with the autonomic nervous system using carbon nanotube (CNT) yarn electrodes [J]. Scientific Reports, 2017, 7: 11723.