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.

这项研究检验了以下假设：前庭系统耳石器官中产生的活性通过自主神经系统影响心血管功能，并有助于维持体位抑制耐受性。 人类受试者的耳石器官将使用特殊设计的离心机在各个方向上通过线性加速有选择性地激活，而使用新开发的微型微功能学装置，直接测量交感神经活动。 在特定的目标1中，相对于旋转轴的不同方向，受试者将以恒定的速度离心，以便相对于头部和身体在广泛的方向和大小范围内存在重力惯性加速度（GIA）的倾斜。 这将确定最大交感神经激活的平面，并检验以下假设：交感神经流出的前庭调节对引力惯性加速度（GIA）载体的特定倾斜度响应。 在离心过程中以不同角度将头部定位在身体上，将控制非vesibular因子的潜在影响。 在特定的目标中，2受试者将以较高的频率（1至3 Hz）的形式进行正弦曲线，并以较低的频率（0.01至0.7 Hz）离心和翻译，以确定最大程度地增加肌肉交感神经神经活性（MSNA）的线性加速度频率。将进行光谱分析以检验以下假设：自主流出与耳石受体的激活不仅沿特定方向，而且在特定频率上有关。 特定目标3检验了耳石有助于维持骨科血液动力学的交感神经流出的增加的假设。 将诱发腿部流体移位，以模拟沿Z轴离心的原位攻击。 这将在旋转中心的头部在头部上进行，因此耳石不会暴露于线性加速度，也不会在旋转中心范围内的速度范围内的旋转中心。 将身体暴露于不同的速度和重力将诱导分级的流体移位变化，这将通过节段的身体阻抗曲线直接测量，并且阻抗和交感活动的变化将相关。 假设在耳石刺激的情况下，MSNA将具有更高的增益，从而揭示了耳石对交感神经激活的贡献。 这项研究完成后，它将增强对耳石 - 同情对线性加速度的理解，在各种方向，频率和大小上，并有助于确定耳石如何有助于维持心血管功能。