OTOLITH INFLUENCES ON SYMPATHETIC ACTIVITY

本研究验证了前庭系统耳石器官产生的活动通过自主神经系统影响心血管功能并有助于维持直立耐受性的假设。人类受试者的耳石器官将使用专门设计的离心机选择性地沿着各个方向以线性加速度激活，而交感神经活动则使用新开发的小型化微神经造影仪直接测量。在具体目标1中，受试者将在相对于旋转轴的不同方向上以恒定速度离心，因此相对于头部和身体的重力惯性加速度（GIA）在很宽的方向和幅度范围内倾斜。这将确定最大交感神经激活的平面，并验证交感神经流出的前庭调节对有关头部的重力惯性加速度（GIA）矢量的特定倾斜作出反应的假设。在离心过程中，将头部以不同角度放置在身体上，可以控制非前庭因素的潜在影响。在具体目标2中，受试者将在较高频率（1至3hz）下进行正弦平移，并在较低频率（0.01至0.7 Hz）下进行离心和平移，以确定最大程度增加肌肉交感神经活动（MSNA）的线性加速度频率。频谱分析将用于验证自主神经流出不仅沿着特定方向，而且在特定频率上与耳石受体的激活有关的假设。特异性目的3验证耳石有助于增加维持直立血流动力学的交感神经流出的假设。通过沿z轴离心法模拟直立挑战，将诱导向腿部的流体移动。这样做的方式有两种，一种是头部在旋转中心，这样耳石就不会受到线性加速度的影响，另一种是头部在一定速度范围内离开旋转中心。将身体暴露在不同的速度和重力下会引起梯度的流体位移变化，这将通过节段体阻抗剖面直接测量，阻抗变化和交感神经活动将相互关联。假设在耳石刺激的情况下，MSNA会有更高的增益，从而揭示了耳石对交感神经激活的贡献。当这项研究完成后，它将加强对耳石交感神经对线性加速度在大范围内的方向、频率和幅度的反应的理解，并有助于确定耳石如何促进心血管功能的维持。

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.