OTOLITH INFLUENCES ON SYMPATHETIC ACTIVITY

耳石对交感神经活动的影响

• 批准号: 6644827
• 负责人: HORACIO KAUFMANN
• 金额: $ 36.43万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6644827
• 关键词: body movement; cardiovascular function; centrifugation; clinical research; human subject; otocyst /otolith; postural hypotension; sympathetic nervous system; vestibular apparatus

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.

本研究验证了前庭系统耳石器官的活动通过自主神经系统影响心血管功能并有助于维持立位耐力的假设。 人类受试者的耳石器官将被选择性地激活与线性加速度沿着各个方向，使用一个专门设计的离心机，而交感神经活动直接测量，使用一个新开发的，微型显微神经成像装置。 在特定目标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，因此重力惯性加速度（GIA）相对于头部和身体在广泛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，并测试交感神经流出的前庭调制响应于重力惯性加速度（GIA）向量相对于头部的特定倾斜的假设。 在离心过程中将头部以不同角度定位在身体上将控制非前庭因素的潜在影响。 在特定目标2中，受试者将以较高频率（1至3 Hz）进行正弦平移，并以较低频率（0.01至0.7 Hz）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。将进行光谱分析以检验以下假设：自主流出不仅与沿着特定方向而且与特定频率的耳石受体激活有关。 特定目标3检验了耳石有助于增加交感神经流出以维持直立性血流动力学的假设。 通过沿Z轴沿着离心，诱导Legward液体移位，模拟直立挑战。 这将在头部位于旋转中心的情况下进行，这样耳石就不会暴露在线性加速度下，或者头部在一定速度范围内偏离旋转中心。 将身体暴露于不同的速度和重力将引起分级的流体移位变化，这将通过节段性身体阻抗曲线直接测量，并且阻抗和交感神经活动的变化将被关联。 据推测，MSNA将有一个更高的增益在耳石刺激的存在下，从而揭示了交感神经激活的耳石的贡献。 当这项研究完成时，它将增强对在广泛的方向，频率和幅度上线性加速度的耳石交感神经反应的理解，并帮助确定耳石如何有助于维持心血管功能。