Tischer Johannes, Szeles Jozsef Constantin, Kaniusas Eugenijus
Institute of Biomedical Electronics, Vienna University of Technology, Vienna, Austria.
Center for Wound Surgery and Special Pain Therapy, Health Service Center, Wiener Privatklinik, Vienna, Austria.
Front Physiol. 2025 Jan 6;15:1495868. doi: 10.3389/fphys.2024.1495868. eCollection 2024.
Neuromodulation comes into focus as a non-pharmacological therapy with the vagus nerve as modulation target. The auricular vagus nerve stimulation (aVNS) has emerged to treat chronic diseases while re-establishing the sympathovagal balance and activating parasympathetic anti-inflammatory pathways. aVNS leads still to over and under-stimulation and is limited in therapeutic efficiency. A potential avenue is personalization of aVNS based on time-varying cardiorespiratory rhythms of the human body. In the pilot study, we propose personalized cardiac-gated aVNS and evaluate its effects on the instantaneous beat-to-beat intervals (RR intervals). Modulation of RR is expected to reveal the aVNS efficiency since the efferent cardiac branch of the stimulated afferent vagus nerve governs the instantaneous RR. Five healthy subjects were subjected to aVNS. Each subject underwent two 25-min sessions. The first session started with the non-gated open-loop aVNS, followed by the systole-gated closed-loop aVNS, then the non-gated, diastole-gated, and non-gated aVNS, each for 5min. In the second session, systole and diastole gated aVNS were interchanged. Changes in RR are analysed by comparing the prolongation of RR intervals with respect to the proceeding RR interval where aVNS took place. These RR changes are considered as a function of the personalized stimulation onset, the stimulation angle starting with R peak. The influence of the respiration phases is considered on the cardiovagal modulation. The results show that the systole-gated aVNS tends to prolong and shorten RR when stimulated after and before the R peak, respectively. The later in time is the stimulation onset within the diastole-gated aVNS, the longer tends to be the subsequent RR interval. The tendency of the RR prolongation raises with increasing stimulation angle and then gradually levels off with increasing delay of the considered RR interval from the one where aVNS took place. The slope of this rise is larger for the systole-gated than diastole-gated aVNS. When considering individual respiration phases, the inspiratory systole-gated aVNS seems to show the largest slope values and thus the largest cardiovagal modulatory capacity of the personalized time-gated aVNS. This pilot study indicates aVNS capacity to modulate the heartbeat and thus the parasympathetic activity which is attenuated in chronic diseases. The modulation is highest for the systole-gated aVNS during inspiration.
神经调节作为一种以迷走神经为调节靶点的非药物疗法受到关注。耳迷走神经刺激（aVNS）已出现用于治疗慢性疾病，同时重建交感迷走平衡并激活副交感抗炎途径。然而，aVNS仍会导致刺激过度和不足，且治疗效率有限。一种潜在途径是基于人体随时间变化的心肺节律对aVNS进行个性化。在这项初步研究中，我们提出个性化心脏门控aVNS，并评估其对瞬时逐搏间期（RR间期）的影响。由于受刺激的传入迷走神经的传出心脏分支控制着瞬时RR，因此预期对RR的调节能揭示aVNS的效率。五名健康受试者接受了aVNS治疗。每位受试者进行了两个25分钟的疗程。第一个疗程从非门控开环aVNS开始，接着是收缩期门控闭环aVNS，然后是非门控、舒张期门控和非门控aVNS，每种持续5分钟。在第二个疗程中，收缩期和舒张期门控aVNS互换。通过比较RR间期相对于进行aVNS时的前一个RR间期的延长情况来分析RR的变化。这些RR变化被视为个性化刺激起始时间以及从R波峰值开始的刺激角度的函数。考虑了呼吸阶段对心脏迷走神经调节的影响。结果表明，收缩期门控aVNS在R波峰值之后和之前受到刺激时，分别倾向于延长和缩短RR。在舒张期门控aVNS中，刺激起始时间越晚，随后的RR间期往往越长。RR延长的趋势随着刺激角度的增加而增加，然后随着与进行aVNS时的RR间期的延迟增加而逐渐趋于平稳。收缩期门控aVNS的这种上升斜率比舒张期门控aVNS更大。当考虑个体呼吸阶段时，吸气时收缩期门控aVNS似乎显示出最大的斜率值，因此在个性化时间门控aVNS中具有最大的心脏迷走神经调节能力。这项初步研究表明aVNS有调节心跳的能力，从而调节在慢性疾病中减弱的副交感神经活动。在吸气期间，收缩期门控aVNS的调节作用最强。
