OTOLITH INFLUENCES ON SYMPATHETIC ACTIVITY

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This research tests the hypothesis that activity arising in the otolith organs of the vestibular system influences cardiovascular function via the autonomic nervous system and contributes to maintenance of orthostatic tolerance. The otolith organs of human subjects will be selectively activated with linear acceleration along various directions, using a specially-designed centrifuge, while sympathetic nerve activity is directly measured, using a newly developed, miniaturized microneurography apparatus. In Specific Aim 1, subjects will be centrifuged at constant velocity in different orientations relative to the axis of rotation, so that there are tilts of gravito-inertial acceleration (GIA) relative to the head and body over a wide range of directions and magnitudes. This will determine the planes of maximal sympathetic activation and test the hypothesis that vestibular modulation of sympathetic outflow responds to specific tilts of the gravito-inertial acceleration (GIA) vector with regard to the head. Positioning the head on the body at different angles during centrifugation will control potential influences of non-vestibular factors. In Specific Aim 2 subjects will be translated sinusoidally at higher frequencies (1 to 3 Hz), and centrifuged and translated at lower frequencies (0.01 to 0.7 Hz) to determine the frequencies of linear acceleration that maximally increase muscle sympathetic nerve activity (MSNA). Spectral analyses will be done to test the hypothesis that autonomic outflow is related to activation of otolith receptors not only along specific directions, but also at specific frequencies. Specific Aim 3 tests the hypothesis that the otoliths contribute to the increase in sympathetic outflow that maintains orthostatic hemodynamics. Legward fluid shifts will be induced that simulate orthostatic challenge using centrifugation along the Z-axis. This will be done either with the head at the center of rotation, so that otoliths are not exposed to linear acceleration or with the head off the center of rotation over a range of velocities. Exposing the body to different velocities and gravitational forces will induce graded fluid shift changes, which will be directly measured via segmental body impedance profiles, and changes in impedance and sympathetic activity will be correlated. It is hypothesized that MSNA will have a higher gain in the presence of otolith stimulation, thereby revealing the contribution of the otoliths to sympathetic activation. When this research is completed, it will enhance understanding of otolith-sympathetic responses to linear acceleration over a wide range of directions, frequencies and magnitudes, and help determine how the otoliths contribute to maintenance of cardiovascular function.