Vasomotor and Sudomotor Activity During Heat Stress in Spinal Cord Injury

脊髓损伤热应激期间的血管舒缩和催汗活动

• 批准号: 10058778
• 负责人: Michelle Trbovich
• 金额: --
• 依托单位: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10058778
• 关键词: Anatomy; Area; Assessment tool; Attenuated; Autonomic Dysfunction; Autonomic nervous system; Award; Blood flow; Body Regions; Botulinum Toxins; Cardiometabolic Disease; Cause of Death; Chronic; Clinical Assessment Tool; Clinical assessments; Complex; Convection; Cutaneous; Development; Diabetes Mellitus; Disease; Efferent Neurons; Exercise; Funding; Future; Goals; Health; Heart Diseases; Heat Stress Disorders; High Prevalence; Homeostasis; Humidity; Imagery; Impairment; Individual; Injury; International; Intervention; Intervention Trial; Iodine; Iontophoresis; Laser-Doppler Flowmetry; Lasers; Lesion; Maps; Measures; Mediating; Mentorship; Mission; Modeling; Monitor; Motor; Nerve; Neurologic; Neurotransmitters; Obesity; Paralysed; Pathway interactions; Peripheral; Personal Satisfaction; Persons; Pharmacology; Physicians; Physiological; Physiology; Population; Quality of life; Reporting; Research; Research Personnel; Research Technics; Risk; Scientist; Sensorimotor functions; Sensory; Skin; Spinal cord injury; Standardization; Starch; Structure; Sweating; Techniques; Temperature; Testing; Toxin; Training; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Vasomotor; Veterans Health Administration; base; body map; career; cholinergic; clinically relevant; experience; improved; innovation; insight; intradermal injection; motor impairment; nerve supply; neuroregulation; noradrenergic; novel; physical conditioning; preservation; presynaptic; presynaptic neurons; prevent; programs; response; skills

Sensory and motor impairment after spinal cord injury (SCI) is well studied and classified with international standardized assessment tools. Meanwhile, autonomic impairment after SCI, is without a standardized clinical assessment tool/exam, is challenging to treat and causes greater impairment in quality of life than paralysis alone.1,2 One sequela of autonomic injury post SCI is thermal dysregulation. It is well accepted that persons with spinal cord injury have impaired ability to regulate core temperature due to compromised thermoregulatory vasomotor and sudomotor activity.3 In the setting of heat stress, impaired cutaneous vasodilation obviates skin blood flow (SkBF) increases and prevents convective cooling while impaired sweating responses (SR) prevents evaporative cooling. As a result, persons with SCI have difficulty maintaining thermal homeostasis, especially under heat stress. Body cooling intervention trials performed to date have all proven minimally successful likely due to lack of clear mechanistic understanding of autonomic change post-SCI. In non-SCI persons, sympathetic cholinergic mechanisms that mediate efferent control of both SkBF and SR are commonly thought to involve one and the same set of nerves; however, definitive proof is lacking. Indeed, cholinergic vasodilator nerves and cholinergic sudomotor nerves could actually be anatomically separate. Interestingly, it has been reported that during heat stress, persons with complete SCI have skin regions where SkBF increases without concomitant SR increases and other regions where SR increases without concomitant SkBF increases.7,8 These results suggest that efferent cholinergic sympathetic vasomotor nerves and efferent cholinergic sympathetic sudomotor nerves are separate, rather one and the same. Being able to study cholinergic vasodilator nerves and cholinergic sudomotor nerves in isolation in SCI will provide a valuable model for thermoregulatory physiology studies in non-SCI and SCI persons, and guide next steps in development of 1) An effective cooling technique so as to minimize heat related illness during exercise in the SCI population with a high prevalence of cardiometabolic disease and 2) A more quantitative assessement of thermoregulatory and autonomic function post-SCI to determine persons at greatest risk of its sequela. OBJECTIVES - To define and test the neurological control mechanisms of sudomotor and vasomotor activity after SCI to determine if their efferent cholinergic control is through an anatomically separate set of nerves. (1) Map areas of vasomotor and sudomotor activity during heat stress in persons with SCI and compare thermoregulatory level of injury (TLOI) with sensorimotor LOI. (2) Test whether increased noradrenergic vasoconstrictor activity attenuates SkBF increases in regions that show SR increases but no SkBF increases during whole body heat stress. (3) Test the hypothesis that cholinergic presynaptic nerve activity effects vasomotor and/or sudomotor responses in regions with discordant SR and SkBF increases during whole body heat stress. METHODS - 50 persons with chronic SCI and 25 AB persons will undergo passive heat stress and areas of sudomotor and vasomotor activity will be outlined. Pharmacologic tests using bretylium iontophoresis and onabotulinum toxin intradermal injections will be utilized to manipulate areas with concordant and discordant vasomotor and sudomotor activity to determine the neurological control mechanisms in each area. Areas of intact thermoregulatory function will be compared to areas of intact sensory and motor function. IMMEDIATE AND LONG TERM CAREER GOALS - Dr. Trbovich's career goals over the next 5 years include expanding her expertise and experience through the proposed research plan, structured training in research skills and mentorship under experienced researchers and clinicians in the field. This opportunity will allow her to develop necessary skills to compete for a VA Merit Review Award in the future. Her long-term goal is to become a VA physician scientist with an independently funded research program that will allow her to significantly contribute to current unanswered questions in the field of autonomic dysfunction after SCI.

脊髓损伤(SCI)后的感觉和运动障碍是国际上广泛研究和分类的。 标准化的评估工具。同时，脊髓损伤后的自主神经损害，还没有标准化的临床研究。 评估工具/检查，治疗具有挑战性，对生活质量的损害比瘫痪更大 1，2脊髓损伤后自主神经损伤的一个后遗症是热失调。人们普遍认为，人们 由于体温调节功能受损，脊髓损伤患者调节核心体温的能力受损 3在热应激环境中，皮肤血管扩张受损可避免皮肤 血流量(SkBF)增加并阻止对流降温，而出汗反应(SR)受损 防止蒸发冷却。因此，脊髓损伤患者很难维持体温平衡， 尤其是在热压力下。到目前为止进行的身体降温干预试验都被证明是最低限度的 成功很可能是因为对脊髓损伤后自主神经变化缺乏明确的机械性理解。在非SCI中 人，交感胆碱能机制，中介传出控制SkBF和SR是 通常认为涉及一组相同的神经；然而，缺乏确凿的证据。的确， 胆碱能血管扩张神经和胆碱能舒缩神经实际上在解剖学上是分开的。 有趣的是，据报道，在热应激期间，患有完全性脊髓损伤的人的皮肤区域 SkBF增加而不伴随SR增加，以及SR增加而不伴随的其他区域 SkBF增加。7，8这些结果提示，传出胆碱能交感血管运动神经和传出 胆碱能交感神经和运动神经是分开的，而不是相同的。能够学习 胆碱能血管扩张神经和胆碱能运动神经在脊髓损伤中的分离将提供有价值的 非脊髓损伤和脊髓损伤患者的体温调节生理学研究模型，并指导下一步 1)开发一种有效的降温技术，以最大限度地减少运动过程中与高温有关的疾病 心脏代谢性疾病高发的脊髓损伤人群和2)更多的定量评估 脊髓损伤后体温调节和自主神经功能以确定其后遗症风险最大的人群。 目的：确定和测试舒缩和血管舒缩活动的神经控制机制。 在脊髓损伤后，以确定他们的传出胆碱能控制是否通过解剖上分离的一组神经。(1) 绘制脊髓损伤患者热应激期间血管运动和运动活动的区域图并进行比较 感觉运动损伤的体温调节水平(TLOI)(2)检测去甲肾上腺素能 血管收缩活性减弱SR增加但无SkBF增加的区域的SkBF增加 在全身热应激期间。(3)检验胆碱能突触前神经活动影响的假设 全身SR和SkBF不协调区域的血管运动和/或运动反应增加 热应激。方法：对50例慢性脊髓损伤患者和25例AB患者进行被动热应激实验。 将概述舒血管运动和血管运动活动的区域。用离子导入法进行药理试验 奥纳波毒素皮内注射将被用来操作符合和 不协调的血管运动和舒缩活动，以确定每个区域的神经控制机制。 体温调节功能完好的区域将与感觉和运动功能完好的区域进行比较。 近期和长期的职业目标--Trbovich博士未来5年的职业目标包括 通过拟议的研究计划、有组织的研究培训来扩展她的专业知识和经验 在该领域有经验的研究人员和临床医生的指导下的技能和指导。这个机会将使她 培养必要的技能，以便将来角逐退伍军人事务部荣誉评审奖。她的长期目标是 成为一名退伍军人事务部内科科学家，拥有一个独立资助的研究项目，这将使她能够 对目前脊髓损伤后自主神经功能障碍领域尚未解答的问题有重大贡献。