ORTHOSTATIC INTOLERANCE IN CFS

描述(申请人提供)：慢性疲劳综合症(CFS)是一种原因不明的常见疾病，使年轻人在最有生产力的年龄段丧失工作能力。有证据表明，立位不耐受可能在CFS患者的疲劳中起作用。该项目广泛的长期目标是描述慢性疲劳综合征(CFS)立位耐受的病理生理学和发病机制；调查立位耐受在CFS症状产生中的作用；利用这一信息制定生理上适当的治疗措施；从而减少疲劳症状。该应用程序的具体目的是：应用小剂量阿托品和氯沙坦增强心脏迷走神经流出，并检测立位应激对心血管的反应；描述交感神经对血管阻力的转导和对立位应激的交感反应；测量立位应激期间跨毛细血管间质液体滤过；确定毛细血管滤过与血浆容量的关系；以及表征脑血流、全身压维持、体位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物刺激的反应来评估动脉压力感受性反射收益；通过将肌肉交感神经活动与外周阻力联系起来来评估交感神经传导；使用埃文斯蓝染色方法测量血浆容量；使用静脉阻塞体积描记术测量静脉顺应性；以及使用经颅多普勒测量脑血流速度。这些措施包括立位耐力要素，将与选定的健康对照组进行比较，以匹配受试者的性别、年龄和体力活动水平。这些变量与用标准化工具确定的体力活动水平和精神状态等协变量的作用之间的关系将使用多变量统计进行分析。

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.