Dynamic blood pressure control and orthostatic tolerance in individuals with MS a

描述(申请人提供)：多发性硬化症(MS)患者中枢神经系统(CNS)轴突髓鞘的破坏或丢失可导致无数症状，包括疲劳、痉挛、头晕和眩晕，以及MS患者的平衡和协调问题。MS患者的下丘脑经常受到MS的影响，导致自主神经和内分泌功能的控制受损。MS中通常观察和描述涉及生殖-尿路、胃肠道、心血管和体温调节系统的自主神经功能障碍。初步证据表明，MS患者血压和心率的神经控制功能受损，立位耐受性降低。此外，众所周知，热应激会加剧MS的临床体征和神经症状。考虑到在热应激期间，其他健康个体的立位耐受性显著降低，部分原因是动脉压力反射控制受损，这一患者群体中的热应激可能会进一步损害心血管功能的神经控制和立位耐受性。两个目标将检验MS对动态血压控制(即压力反射功能)和相关的控制机制(即神经、心脏和外周血管反应)以及立位耐受性的生理学后果：1.MS患者的静息动脉压力反射功能是否受损？2.MS患者的立位耐受性和对立位挑战的压力反射反应性是否受损？重要的基础和临床信息将从拟议的研究中获得，通过新的已建立的技术的应用，这些技术以前没有用于这种疾病的研究。这些研究的结果将为MS患者血压反应受损的机制提供新的信息。了解这些机制可能为临床医生提供有价值的潜在治疗策略信息，并改善MS患者的日常生活。此外，将获得有关热应激在调节MS神经心血管反应方面的潜在影响的重要信息。总之，拟议工作的发现有可能导致开发新的治疗策略，旨在对抗MS患者在中温和热应激条件下的有害心血管和神经变化。事实上，如果正如初步数据显示的那样，动脉压力反射功能受损被确定为MS患者立位耐力受损的潜在机制，那么我们将能够寻求能够改善血压调节并潜在抵消这种疾病所表现的有害神经心血管反应的治疗/干预措施。

DESCRIPTION (provided by applicant): Disruption or loss of axonal myelin in the central nervous system (CNS) with multiple sclerosis (MS) can lead to a myriad of symptoms including fatigue, spasticity, dizziness and vertigo, and balance and coordination problems in individuals with MS. The hypothalamus is frequently affected by MS, resulting in impaired control of autonomic and endocrine function. Autonomic dysfunction involving the genito-urinary, gastrointestinal, cardiovascular, and thermoregulatory systems are commonly observed and described in MS. Preliminary evidence suggests impairments in the neural control of blood pressure and heart rate in individuals with MS, as well as reductions in orthostatic tolerance. In addition, heat stress is known to exacerbate clinical signs and neurological symptoms of MS. Given that orthostatic tolerance is markedly reduced during heat stress in otherwise healthy individuals, in part due to impairments in arterial baroreflex control, it is likely that heat stres in this patient population would further impair neural control of cardiovascular function and orthostatic tolerance. Two aims will examine the physiologic consequences of MS on dynamic blood pressure control (i.e., baroreflex function) and the associated control mechanisms (i.e., neural, cardiac, and peripheral vascular responsiveness), as well as orthostatic tolerance in this population: 1. Is resting arterial baroreflex function impaired in MS patients? 2. Is orthostatic tolerance and arterial baroreflex responsiveness to orthostatic challenge during thermoneutral and heat stress conditions impaired in MS patients? Important basic and clinical information will be gained from the proposed studies through the novel application of established techniques that have not been previously used in the study of this disease. The findings obtained from these studies should provide novel information about the mechanisms contributing to the impaired blood pressure response in MS patients. Understanding these mechanisms may provide valuable information to clinicians for potential treatment strategies and improve the day-to-day lives of individuals with MS. Further, important information will be garnered in regard to the potential influences of heat stress in modulating neural cardiovascular responses in MS. Overall, the findings from the proposed work have the potential to lead to development of novel therapeutic strategies targeted at countering the deleterious cardiovascular and neural alterations in individuals with MS during thermoneutral and heat stress conditions. Indeed, if as preliminary data suggest, impairments in the arterial baroreflex function are identified as the underlying mechanism for impairments in orthostatic tolerance in MS patients, we will then be able to pursue therapies/interventions that could improve blood pressure regulation and potentially offset the deleterious neural cardiovascular responsiveness that manifests with this disease.