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

描述（由申请人提供）：多发性硬化症（MS）患者中枢神经系统（CNS）轴突髓磷脂的破坏或丧失可导致多种症状，包括疲劳、痉挛、头晕和眩晕、平衡和协调问题。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。自主神经功能障碍包括泌尿生殖系统、胃肠系统、心血管系统和体温调节系统，在多发性硬化症中经常被观察和描述。初步证据表明，多发性硬化症患者血压和心率的神经控制受损，以及直立耐受性降低。此外，已知热应激可加重ms的临床体征和神经系统症状。鉴于健康个体在热应激时直立耐受性明显降低，部分原因是动脉压力反射控制受损，因此该患者群体的热应激可能会进一步损害心血管功能和直立耐受性的神经控制。两个目的将检查MS对动态血压控制（即压力反射功能）和相关控制机制（即神经、心脏和周围血管反应性）的生理后果，以及该人群的直立耐受性：1。MS患者静息动脉压力反射功能受损吗？2. 在热中性和热应激条件下，MS患者的直立耐受性和动脉压力反射反应是否受损？重要的基础和临床信息将从拟议的研究中获得，通过对以前未用于该疾病研究的现有技术的新应用。从这些研究中获得的发现应该为MS患者血压反应受损的机制提供新的信息。了解这些机制可以为临床医生提供潜在的治疗策略和改善ms患者的日常生活提供有价值的信息。此外，关于热应激在调节ms神经心血管反应中的潜在影响，将获得重要的信息。这项工作的发现有可能导致新的治疗策略的发展，针对MS患者在热中性和热应激条件下的有害心血管和神经改变。事实上，如果像初步数据显示的那样，动脉压力反射功能的损伤被确定为MS患者直立耐受性损伤的潜在机制，那么我们将能够寻求可以改善血压调节的治疗/干预措施，并可能抵消这种疾病所表现出的有害的神经心血管反应性。

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.