Targeted Transcutaneous Stimulation to Restore Autonomic Cardiovascular Health in Veterans with Spinal Cord Injury

项目概要/摘要 博士Caitlyn Katzelnick一直在与国家脊柱中心的研究人员合作， 脊髓损伤（SCI）和固定条件在VA医疗中心，布朗克斯，纽约州八 多年担任高级研究协调员。沿着她的主要导师韦希特博士，凯特琳 一直在研究SCI后心血管、脑血管和认知功能障碍的影响， 她的博士论文的结果表明， 脊髓损伤患者的交感神经功能紊乱程度可能与 控制和增加对肾素-血管紧张素-醛固酮系统（RAAS）的依赖， 维持直立位血压（BP）。最近的证据表明， 动脉硬度是心血管疾病风险的独立预测因子， 导致SCI患者心血管发病率和死亡率升高， 一般人口。增加对RAAS的依赖被认为可以减轻直立性福尔斯， BP和降低症状报告的严重程度;然而，在一般人群中的发现 RAAS与血管重构和重塑有关。因此，临床干预， 稳定和正常血压应该是SCI患者优先考虑。进展 脊突的神经调节方法提供了一种非药理学方法 恢复内源性自主心血管控制，改善直立位血压控制。 根据我们目前对脊髓内躯体内脏整合的理解， 经皮脊髓刺激（TSCS）可以靶向激发和 调节适当的脊髓自主神经回路以快速使直立性BP正常化;然而， 需要电极放置和刺激参数标测来优化直立位BP 控制因此，我们的主要目标是使用非侵入性方法识别个性化地图， 脊髓自主神经回路的TSCS，导致坐位BP增加。我们的次要 目的是比较血压，血浆去甲肾上腺素，肾素和醛固酮浓度， 在有和没有最佳TSCS情况下的头向上倾斜。本次调查将在品牌- 新的脊柱刺激中心，位于凯斯勒基金会，这是我们的VA 卫星中心卡泽尼克博士可以使用所有必要的设施和设备 包括：TSCS、肌电图（EMG）和心血管。CDA-1将提供博士。 Katzelnick拥有先进的技能培训，临床研究经验和指导， 帮助她成长为退伍军人事务部的独立调查员培训目标包括：1） 管理和映射TSCS; 2）了解EMG记录， 分析;和3）测定RAAS激素。Katzelnick博士将参加学术课程， 推进她的知识基础，在赠款写作，心血管生理学，统计学，生物物理学 还有EMG她的导师包括各种相关的科学背景，这些背景与 对SCI后继发性后果的类似理解。预计这些数据 将开始建立脊髓自主神经回路TSCS标测的标准方法， 促进心血管健康的恢复，以及退伍军人的整体福祉， 固定化条件。日后的拨款将采用划一的教师资助计划方法 应用程序，包括CDA-2应用程序，以促进改善活力和生活质量， 退伍军人SCI

PROJECT SUMMARY/ABSTRACT Dr. Caitlyn Katzelnick has been working with investigators in the National Center for Spinal Cord Injury (SCI) and Immobilizing Conditions at the VA Medical Center, Bronx, NY for eight years as a senior research coordinator. Along with her Primary Mentor, Dr. Wecht, Caitlyn has been studying the effects of cardiovascular, cerebrovascular and cognitive dysfunction post SCI, and the results of her Doctoral dissertation suggest that increased arterial stiffness in individuals with SCI may relate to the degree of decentralized sympathetic cardiovascular control and increased reliance on the renin-angiotensin-aldosterone system (RAAS) for maintenance of orthostatic blood pressure (BP). Recent evidence indicates that increased arterial stiffness is an independent predictor of cardiovascular disease risk, which may contribute to the heightened cardiovascular morbidity and mortality in the SCI, compared to the general population. Increased reliance on the RAAS is believed to mitigate orthostatic falls in BP and reduce the severity of symptoms reporting; however, findings in the general population link the RAAS with vascular restructuring and remodeling. Therefore, clinical intervention to stabilize and normalize BP should be a priority in hypotensive individuals with SCI. Advances in methods of neuromodulation of the spinal processes offer a non-pharmacologic approach to restore endogenous autonomic cardiovascular control and improve orthostatic BP control. Based on our present understanding of the somatovisceral integration within the spinal cord, it is plausible that transcutaneous spinal cord stimulation (TSCS) can be targeted to excite and modulate appropriate spinal autonomic circuitry to rapidly normalize orthostatic BP; however, electrode placement and stimulation parameter mapping is needed to optimize orthostatic BP control. Therefore, our primary aim is to identify an individualized map using noninvasive TSCS of the spinal autonomic circuitry that results in an increase of seated BP. Our secondary aim is to compare BP, plasma concentrations of norepinephrine, renin and aldosterone during a head-up tilt with and without optimal TSCS. This investigation will be completed at the brand- new Center of Spinal Stimulation, located at the Kessler Foundation, which is home to our VA satellite center. Dr. Katzelnick will have access to all the necessary facilities and equipment including: TSCS, electromyography (EMG) and cardiovascular. The CDA-1 will provide Dr. Katzelnick with the advanced skill training, clinical research experience, and mentorship to facilitate her growth into an independent VA investigator. Training objectives include: 1) administering and mapping TSCS; 2) gaining an understanding of EMG recordings and analysis; and 3) assaying the RAAS hormones. Dr. Katzelnick will take academic courses to advance her knowledge base in grant writing, cardiovascular physiology, statistics, biophysics and EMG. Her mentors encompass various relevant scientific backgrounds, which converge with a similar understanding of secondary consequences after a SCI. It is anticipated that these data will begin to establish a standard methodology for TSCS mapping of spinal autonomic circuits to promote restoration of cardiovascular health, and overall well-being in Veterans with immobilizing conditions. Standardized TSCS methodology will be used in future grant applications, including a CDA-2 application, to promote improved vitality and quality of life in Veterans with SCI.