Cohen Bernard, Martinelli Giorgio P, Xiang Yongqing, Raphan Theodore, Yakushin Sergei B
Department of Neurology, Icahn School of Medicine at Mount Sinai , New York, NY , USA.
Department of Computer and Information Science, Brooklyn College, City University of New York , New York, NY , USA.
Front Neurol. 2017 Mar 15;8:83. doi: 10.3389/fneur.2017.00083. eCollection 2017.
Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long-Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20-50 mmHg and ≈20-50 beats/min (bpm) into a vasovagal response when stimulated with Sgv\S in susceptible rats. As the rats were continually stimulated, HR initially rose to counteract the fall in BP; then the increase in HR became more substantial and long lasting, effectively opposing the fall in BP. Finally, the vestibular stimuli simply caused an increase in BP, the normal sequence following activation of the VSR. Concurrently, habituation caused disappearance of the low-frequency (0.025 and 0.05 Hz) oscillations in BP and HR that must be present when vasovagal responses are induced. Habituation also produced significant increases in baroreflex sensitivity ( < 0.001). Thus, repeated low-frequency activation of the VSR resulted in a reduction and loss of susceptibility to development of vasovagal responses in rats that were previously highly susceptible. We posit that reactivation of the baroreflex, which is depressed by anesthesia and the disappearance of low-frequency oscillations in BP and HR are likely to be critically involved in producing resistance to the development of vasovagal responses. SGVS has been widely used to activate muscle sympathetic nerve activity in humans and is safe and well tolerated. Potentially, it could be used to produce similar habituation of vasovagal syncope in humans.
血管迷走性晕厥是一个没有有效治疗方法的重大医学问题，据推测与压力反射功能衰竭有关。虽然一些研究表明，反复进行静态倾斜试验可以阻止血管迷走性晕厥，但其他研究并未发现这一点。我们使用对血管迷走反应高度敏感的麻醉雄性Long-Evans大鼠，发现用±2和±3 mA、0.025 Hz的正弦电刺激前庭刺激（sGVS）反复激活前庭交感反射（VSR）会导致血压（BP）和心率（HR）的渐进性变化，从而阻止血管迷走反应的进一步产生。最初，在易感大鼠中用Sgv\S刺激时，血压和心率会下降约20 - 50 mmHg和约20 - 50次/分钟（bpm），进入血管迷走反应状态。随着大鼠不断受到刺激，心率最初会上升以抵消血压下降；然后心率的增加变得更加显著且持久，有效地对抗了血压下降。最后，前庭刺激只会导致血压升高，这是激活VSR后的正常顺序。同时，习惯化导致血压和心率中的低频（0.025和0.05 Hz）振荡消失，而在诱发血管迷走反应时这些振荡必须存在。习惯化还使压力反射敏感性显著增加（<0.001）。因此，反复低频激活VSR导致先前高度易感的大鼠对血管迷走反应的易感性降低并丧失。我们认为，压力反射的重新激活（其因麻醉而受到抑制）以及血压和心率中低频振荡的消失可能与产生对血管迷走反应发展的抵抗力密切相关。SGVS已被广泛用于激活人类肌肉交感神经活动，且安全且耐受性良好。潜在地，它可用于在人类中产生类似的血管迷走性晕厥习惯化。
