ORTHOSTATIC INTOLERANCE IN CFS

描述（由申请人提供）：慢性疲劳综合征（CFS）是一种原因不明的常见疾病，使年轻人在最具生产力的年份丧失能力。有证据表明，立位不耐受可能在CFS患者的疲劳中发挥作用。该项目广泛的长期目标是描述慢性疲劳综合征（CFS）中直立不耐受的病理生理学和发病机制;调查直立不耐受在产生CFS症状中的作用;利用这些信息制定生理学上适当的治疗干预措施;从而减少疲劳症状。本申请的具体目的是用低剂量阿托品和伊奥沙坦增强心迷走神经流出，并检查对直立应激的心血管反应;表征下肢血管阻力的交感神经转导，并表征下肢对直立应激的交感神经反应;测定立位应激时经毛细血管间质液滤过率，探讨毛细血管滤过率与血浆容量的关系;并表征脑血流、全身压力维持、姿势性心动过速和副交感神经流出。我们将通过测量心率和肌肉交感神经活动对药理学刺激的反应来评估动脉压力反射增益;通过将肌肉交感神经活动与外周阻力相关联来评估交感神经转导;使用伊文思蓝染料法来评估血浆容量;使用静脉闭塞体积描记法来评估静脉顺应性;以及使用经颅多普勒来评估脑血流速度。将这些测量（包括立位耐力要素）与选择的健康对照进行比较，以匹配受试者的性别、年龄和体力活动水平。将使用多变量统计分析这些变量与协变量（如体力活动水平和精神状态）之间的关系，这些协变量采用标准化工具确定。

DESCRIPTION (provided by applicant): The chronic fatigue syndrome (CFS) is a common disorder of unknown cause that incapacitates young individuals in their most productive years. There is evidence that orthostatic intolerance may play a role in the fatigue of patients with CFS. The broad long-term objectives of the project are to delineate the pathophysiology and pathogenesis of orthostatic intolerance in the chronic fatigue syndrome (CFS); to investigate the role of orthostatic intolerance in producing the symptoms of CFS; to use this information to institute physiologically appropriate therapeutic interventions; and thereby decrease the symptoms of fatigue. The Specific Aims of the application are to enhance cardiovagal outflow with low dose atropine and Iosartan and examine the cardiovascular response to orthostatic stress; to characterizing sympathetic nervous transduction to vascular resistance in the lower limbs and characterize the sympathetic responses in the lower limbs to orthostatic stress; to measure transcapillary interstitial fluid filtration during orthostatic stress determine the relationship between capillary filtration and plasma volume; and characterize cerebral blood flow, systemic pressure maintenance, postural tachycardia and parasympathetic outflow. We will assess arterial baroreflex gain by measuring the heart rate and muscle sympathetic nerve activity response to pharmacological provocations; sympathetic transduction by relating muscle sympathetic nerve activity to peripheral resistance; plasma volume using the Evans Blue dye method; venous compliance using venous occlusion plethysmography; and cerebral blood flow velocity with transcranial Doppler. These measures, which comprise the elements of orthostatic tolerance, will be compared with healthy controls selected to match the gender, age and level of physical activity of the subjects. The relationships between these variables and role of covariates such as the level of physical activity and psychiatric state, determined with standardized instruments, will be analyzed using multivariate statistics.