Neurogenic (vasovagal) syncope (VVS) is a significant medical problem. The faint is preceded by a Vasovagal Response (VVR), characterized by a sudden drop in arterial blood pressure (BP) and heart rate (HR). VVS and VVRs are diagnosed using a tilt test, a vestibular stimulus. Despite being relatively common, the neural basis of the VVR and the role of the vestibular system in inducing VVRs are not known. Moreover, there is no small animal model of VVRs. We recently showed that low frequency sinusoidal galvanic vestibular stimulation (sGVS) induces VVRs in anesthetized rats. As in humans, VVRs are also induced in rats by tilt. In the proposed research we will characterize the physiological properties of VVRs in rats, thereby establishing a useful small animal model of human VVRs. We propose that VVRs are induced by strong, repeated stimulation of the vestibulo-sympathetic reflex (VSR), which maintains blood flow to the brain during changes in head position relative to gravity.
Aim 1 will characterize the transitions from normal VSR to VVRs using pulses and sinusoids of galvanic stimulation to show that VVRs occur when the VSR is appropriately stimulated. Nose up tilt and Translation-While-Rotating (TWR) will be used to determine the axes of stimulation that are most likely to produce VVRs. Additionally, the low frequency oscillations in HR and BP that are produced by sGVS and tilt reflect activation of Mayer waves, thought to be of fundamental importance in maintaining BP stability.
In Aim 2 these oscillations will be modeled using a novel concept in which Mayer wave function is represented by a non-linear relaxation oscillator.
In Aim 3, single unit neurophysiological studies in otolith-recipient portions of the caudal vestibular nuclei will identify the functional characteristics and physiological signature of VVR- related neurons. Together, the proposed research will establish a model of VVS, document how the vestibular system controls BP, and demonstrate that VVRs are adaptive compensatory responses that serve to re- equilibrate BP after major perturbations.

Public Health Relevance

Vasovagal syncope (VVS;unexpected fainting) and vasovagal responses (VVR) are a significant medical problem when they recur frequently;the underlying causes and neural mechanisms that produce such fainting are unknown. We have recently shown that activation of the vestibular system causes arterial blood pressure and heart rate changes in anesthetized rats that are similar to the changes in humans during these faints. In this project, we will characterize the changes in blood pressure and heart rate that are produced by activation of the vestibular system with tilts and galvanic stimulation, model the process that is causing the faints with a novel relaxation oscillator, and investigate the underlying neuronal basis for these responses.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC012573-02
Application #
8624688
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Platt, Christopher
Project Start
2013-03-01
Project End
2016-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$344,886
Indirect Cost
$117,519
Name
Icahn School of Medicine at Mount Sinai
Department
Neurology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Dai, Mingjia; Cohen, Bernard; Smouha, Eric et al. (2014) Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome. Front Neurol 5:124
Yakushin, Sergei B; Martinelli, Giorgio P; Raphan, Theodore et al. (2014) Vasovagal oscillations and vasovagal responses produced by the vestibulo-sympathetic reflex in the rat. Front Neurol 5:37
Cohen, Bernard; Martinelli, Giorgio P; Raphan, Theodore et al. (2013) The vasovagal response of the rat: its relation to the vestibulosympathetic reflex and to Mayer waves. FASEB J 27:2564-72