Investigator's Application): The over-all objectives of this proposal are: (1) to delineate the pathophysiology and pathogenesis of orthostatic intolerance in the chronic fatigue syndrome (CFS) (2) to investigate the role of orthostatic intolerance in producing the symptoms of CFS and (3) to use this information to apply physiologically appropriate therapeutic interventions and thereby decrease the symptoms of fatigue. The investigators plan to determine the physiological characteristics of orthostatic intolerance in CFS patients and healthy controls, characterize the differences in functional exercise capacity among CFS patients and between CFS patients and controls; and identify the relationships between the physiological measures of orthostatic intolerance, measures of functional exercise capacity, symptoms of orthostatic intolerance and symptoms of fatigue. Cardiovascular autonomic functions are to be assessed using standard tests of the sympathetic and parasympathetic nervous system; arterial baroreflex gain is to be measured using the heart rate and muscle sympathetic nerve activity response to pharmacological provocations; the cardiopulmonary baroreflex functions is to be assessed in response to graded central hypovolemia elicited by lower body negative pressure; plasma volume will be measured using the Evans Blue dye method; venous compliance assessed with venous occlusion plethysmography, Assessment of neurohumoral status and the functional exercise capacity is also to be included. These measures, which comprise the elements of orthostatic tolerance, will be compared with matched healthy controls. The relationships between these variables and the role of covariates such as the level of physical activity and psychiatric state, determined with standardized instruments, are to be analyzed using multivariate statistics.
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