Annoni Elizabeth M, Xie Xueyi, Lee Steven W, Libbus Imad, KenKnight Bruce H, Osborn John W, Tolkacheva Elena G
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Cyberonics Inc., Houston, TX, USA.
Physiol Rep. 2015 Aug;3(8). doi: 10.14814/phy2.12476.
Hypertension (HTN) is the single greatest risk factor for potentially fatal cardiovascular diseases. One cause of HTN is inappropriately increased sympathetic nervous system activity, suggesting that restoring the autonomic nervous balance may be an effective means of HTN treatment. Here, we studied the potential of vagus nerve stimulation (VNS) to treat chronic HTN and cardiac arrhythmias through stimulation of the right cervical vagus nerve in hypertensive rats. Dahl salt-sensitive rats (n = 12) were given a high salt diet to induce HTN. After 6 weeks, rats were randomized into two groups: HTN-Sham and HTN-VNS, in which VNS was provided to HTN-VNS group for 4 weeks. In vivo blood pressure and electrocardiogram activities were monitored continuously by an implantable telemetry system. After 10 weeks, rats were euthanized and their hearts were extracted for ex vivo electrophysiological studies using high-resolution optical mapping. Six weeks of high salt diet significantly increased both mean arterial pressure (MAP) and pulse pressure, demonstrating successful induction of HTN in all rats. After 4 weeks of VNS treatment, the increase in MAP and the number of arrhythmia episodes in HTN-VNS rats was significantly attenuated when compared to those observed in HTN-Sham rats. VNS treatment also induced changes in electrophysiological properties of the heart, such as reduction in action potential duration (APD) during rapid drive pacing, slope of APD restitution, spatial dispersion of APD, and increase in conduction velocity of impulse propagation. Overall, these results provide further evidence for the therapeutic efficacy of VNS in HTN and HTN-related heart diseases.
高血压(HTN)是潜在致命性心血管疾病的最大单一风险因素。HTN的一个病因是交感神经系统活动不适当增加,这表明恢复自主神经平衡可能是治疗HTN的有效手段。在此,我们通过刺激高血压大鼠的右颈迷走神经,研究了迷走神经刺激(VNS)治疗慢性HTN和心律失常的潜力。将 Dahl 盐敏感大鼠(n = 12)给予高盐饮食以诱导 HTN。6周后,将大鼠随机分为两组:HTN-假手术组和HTN-VNS组,其中对HTN-VNS组进行4周的VNS治疗。通过植入式遥测系统连续监测体内血压和心电图活动。10周后,对大鼠实施安乐死并取出心脏,使用高分辨率光学标测进行离体电生理研究。六周的高盐饮食显著增加了平均动脉压(MAP)和脉压,表明所有大鼠均成功诱导出HTN。VNS治疗4周后,与HTN-假手术组相比,HTN-VNS大鼠的MAP升高和心律失常发作次数显著减少。VNS治疗还引起了心脏电生理特性的变化,例如在快速驱动起搏期间动作电位持续时间(APD)缩短、APD恢复斜率、APD的空间离散度降低以及冲动传导速度增加。总体而言,这些结果为VNS在HTN和HTN相关心脏病中的治疗效果提供了进一步的证据。