Vestibular Activation Habituates the Vasovagal Response in the Rat.

Bernard Cohen,Yongqing Xiang,Giorgio P Martinelli,Sergei B Yakushin,Theodore Raphan

doi:10.3389/fneur.2017.00083

Abstract

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 (p < 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.

Highlights

Vasovagal syncope is a significant medical problem [3,4,5,6]
This was demonstrated in two sets of rats: seven rats that were initially susceptible to the generation of vasovagal responses and were utilized in other experiments lost their susceptibility when they were stimulated at different intervals with various forms of vestibular stimulation (Figure 1C)
This was shown by the close study of four rats that were susceptible to the generation of vasovagal responses and lost that susceptibility when the vestibulosympathetic reflex (VSR) was repeatedly stimulated with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS)

Summary

Introduction

The symptoms that lead to vasovagal syncope and the preceding vasovagal response that underlies syncope have been well described [5, 7, 8], and the reductions in blood pressure (BP), heart rate (HR), and baroreflex sensitivity associated with syncope are known [7, 9,10,11]. A model of the vasovagal response has suggested, that a fall in desired BP could be the critical signal that initiates the combined fall in BP and HR [14]. Where such a signal would arise and how it is transmitted is still unknown. There has been no effective therapy for vasovagal syncope

Objectives

Methods

Conclusion