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

项目摘要/摘要 凯特琳·卡泽尔尼克博士一直在与国家脊柱中心的研究人员合作 纽约布朗克斯退伍军人医学中心的脊髓损伤(SCI)和固定条件，共8人 多年担任高级研究协调员。与她的主要导师韦克特博士一起，凯特琳 一直在研究脊髓损伤后对心脑血管和认知功能障碍的影响， 她的博士论文的结果表明，动脉僵硬增加 脊髓损伤个体可能与分散交感神经心血管的程度有关 控制和增加对肾素-血管紧张素-醛固酮系统(RAAS)的依赖 维持立位血压(BP)。最近的证据表明， 动脉僵硬是心血管疾病风险的独立预测因子，这可能 导致脊髓损伤的心血管发病率和死亡率升高，与 普通人口。增加对RAAS的依赖被认为可以减少直立性跌倒 BP和降低症状报告的严重性；然而，在普通人群中的研究结果 将RAAS与血管重构和重塑联系起来。因此，临床干预对 对患有脊髓损伤的低血压患者来说，稳定和正常化血压应该是首要任务。最新进展 脊椎突起的神经调节方法提供了一种非药物治疗方法 恢复内源性自主心血管控制，改善立位血压控制。 根据我们目前对脊髓内躯体内脏整合的理解，它 经皮脊髓刺激(TSCS)可以有针对性地刺激和 调节适当的脊髓自主神经回路以迅速使立位血压正常化；然而， 需要电极放置和刺激参数映射来优化直立位BP 控制力。因此，我们的主要目标是使用非侵入性识别个性化地图 导致坐位血压增加的脊髓自主神经回路的TSCS。我们的次要 目的是比较高血压患者血压、血浆去甲肾上腺素、肾素和醛固酮的浓度。 具有和不具有最佳TSCS的头朝上倾斜。此次调查将在该品牌完成- 新的脊椎刺激中心，位于凯斯勒基金会，是我们退伍军人管理局的总部 卫星中心。卡泽尔尼克博士将可以使用所有必要的设施和设备 包括：TSCS、肌电(EMG)和心血管。CDA-1将为DR提供。 Katzelnick拥有先进的技能培训、临床研究经验和指导 帮助她成长为一名独立的退伍军人事务部调查员。培训目标包括：1) 管理和映射TSCS；2)了解肌电记录和 分析；3)RAAS激素测定。卡泽尔尼克博士将带着学术课程 提升她在助学金撰写、心血管生理学、统计学、生物物理学方面的知识基础 还有肌电。她的导师涵盖了各种相关的科学背景，这些背景与 对脊髓损伤后的次要后果有类似的理解。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，以 促进退伍军人心血管健康和整体幸福感的恢复 固定条件。未来的赠款将使用标准化的TSCS方法 应用程序，包括CDA-2应用程序，以促进改善生活活力和质量 患有SCI的退伍军人。

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.