Vestibular Contributions to Orthostasis

前庭对直立的贡献

• 批准号: 8303626
• 负责人: CHESTER A RAY
• 金额: $ 22.95万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8303626
• 关键词: American; Blood Vessels; Data; Development; Devices; Disease; Dysautonomias; Foundations; Goals; Head; Human; Hypotension; Individual; Intervention; Kidney; Knowledge; Leg; Mastoid process; Measures; Mediating; Methods; Muscle; Nerve; Orthostasis; Orthostatic Hypotension; Patients; Peripheral; Reflex action; Regulation; Research; Risk Factors; System; Testing; Time; Ultrasonics; Vascular resistance; Work; alternative treatment; base; blood pressure regulation; bone; cohort; expectation; experience; improved; innovation; mortality; novel; research study; response; sound

DESCRIPTION (provided by applicant): It is estimated that over 500,000 Americans suffer with orthostatic intolerance. Despite the magnitude of the number, this condition is still poorly understood and treated. In the past decade, evidence has accumulated demonstrating that the vestibular system contributes to postural blood pressure regulation. However, despite this knowledge, no intervention has been developed to activate the vestibular system and to improve orthostatic intolerance. Our long-term goal of this project is to further our understanding of how activation of the vestibular system participates in orthostasis in humans. The specific objectives of this R21 proposal are to: 1) examine the effect of ultrasonic bone stimulation of the mastoid (UBS) on muscle sympathetic nerve activity (MSNA) and vascular resistance, and 2) determine if UBS improves orthostatic tolerance in humans. The central hypotheses are that UBS augments MSNA and improves orthostatic intolerance in humans. We formulated these hypotheses, in part, based upon our strong preliminary data. As presented in the Preliminary Studies, we found that UBS increases MSNA and improves orthostatic tolerance in humans who have diminished capacity. The rationale for the proposed research is that once we know that UBS can increase MSNA and improve orthostatic intolerance, alternative treatments can be developed to assist patients who suffer from this disorder. We will pursue our objectives via two specific aims. Aim 1: To determine MSNA and vascular responses to UBS. Our working hypothesis for this aim is that UBS increases MSNA and vascular resistance to the leg and kidney in humans. This finding will be novel because no previous studies have used UBS to activate MSNA in humans. Aim 2: To determine if UBS improves orthostatic tolerance during head-up tilt. Our working hypothesis for this aim is that UBS improves orthostatic tolerance during head-up tilt. We will test this hypothesis by measuring the duration of head-up tilt with and without UBS in subjects that are afflicted by orthostatic intolerance. The findings will be novel because it will be the first time that UBS has been demonstrated to improve orthostatic intolerance in humans. Additionally, we will test a cohort of older subjects (>55 yr). Older individuals are more prone to orthostatic intolerance than younger subjects. In these studies, we will examine the prediction that UBS augments MSNA and improves orthostatic tolerance in humans. The proposed work is innovative because 1) it uses a new external device (i.e., UBS) to stimulate MSNA and 2) uses UBS to improve orthostatic intolerance in humans. At the completion of this project, it is our expectation that this work will have important implications i understanding the cause and the development of possible new treatment of orthostatic intolerance in otherwise healthy subjects. PUBLIC HEALTH RELEVANCE: The current project will contribute to our understanding the vestibular contributions to postural-mediated sympathetic activation and its relation to orthostati intolerance or hypotension in humans. Orthostatic hypotension is a risk factor for increased mortality in humans.

描述(由申请人提供)：据估计，超过50万美国人患有直立不耐受。尽管这个数字很大，但人们对这种疾病的了解和治疗仍然很少。在过去的十年里，越来越多的证据表明，前庭系统对体位血压调节有贡献。然而，尽管有了这些知识，还没有开发出任何干预措施来激活前庭系统和改善立位耐受性。我们这个项目的长期目标是加深我们对 前庭系统的激活如何参与人类的直立。该R21方案的具体目标是：1)检查超声骨刺激对 乳突(UBS)对肌肉交感神经活动(MSNA)和血管阻力的影响，以及2)确定UBS是否改善了人类的立位耐力。核心假设是，瑞银增强了MSNA，改善了人类的立位耐受性。我们提出了这些假设，部分是基于我们强大的初步数据。正如在《初步研究》中所介绍的，我们发现瑞银增加了MSNA，并改善了能力减弱的人的立位耐力。提出这项研究的理由是，一旦我们知道瑞银可以增加MSNA并改善立位耐受性，就可以开发替代疗法来帮助患有这种疾病的患者。我们将通过两个具体目标来实现我们的目标。目的1：确定MSNA和血管对瑞银的反应。我们对这一目标的工作假设是，瑞银增加了人类腿部和肾脏的MSNA和血管阻力。这一发现将是新的，因为之前没有研究使用瑞银来激活人类的MSNA。目的2：确定瑞银是否改善了直立倾斜时的立位耐力。我们的工作假设是，瑞银集团可以在直立倾斜时提高立位耐力。我们将通过测量在有和没有瑞银的情况下患有立位不耐受的受试者的直立倾斜持续时间来检验这一假说。这一发现将是新的，因为这将是瑞银首次被证明可以改善人类的直立不耐受。此外，我们还将测试一组年龄较大的受试者(55岁)。年龄较大的人比年轻的人更容易出现直立不耐受。在这些研究中，我们将检验瑞银增强MSNA和改善人体立位耐力的预测。这项拟议的工作具有创新性，因为1)它使用一种新的外部设备(即UBS)来刺激MSNA，以及2)使用UBS来改善人类的立位耐受性。在这个项目完成后，我们期望这项工作将对我了解直立不耐受的原因和其他健康受试者可能的新治疗方法的发展产生重要影响。 公共卫生相关性：目前的项目将有助于我们理解前庭对体位介导的交感神经激活的贡献，以及它与人类直立不耐受或低血压的关系。直立性低血压是人类死亡率增加的一个危险因素。