Project: Research project

Project Details


The pathogenesis of the chronic fatigue syndrome (CFS) includes
severe and debilitating fatigue, orthostatic intolerance, and the disruption of
hematological, autonomic, and cardiovascular function. Our preliminary findings
suggest that: 1) reduced red blood cell (RBC) mass is a critical hematological
marker of CFS; and 2) RBC mass expansion improves orthostatic tolerance and
fatigue beyond that ascribed to plasma volume expansion alone. However, the
physiologic mechanisms underlying the RBC mass treatment effect and the
relationship of such mechanisms to individual differences in treatment response
have not been elucidated. This proposed 5-year study will screen 150
CDC-defined CFS men and women and classify them into low and normal RBC mass
groups. The CFS subjects (90 of 105 enrolled) will be studied before and after
a 3-month intervention in a randomized double-blind, placebo-controlled study
of pharmacotherapy to expand RBC mass; specifically, two CFS groups with low
RBC (RBC-treated and placebo-treated) will be compared to another CFS group
with normal RBC mass (standard and usual care). To assess whether the
diminished cardiac function, characteristic of CFS orthostatic intolerance, is
a consequence of myocardial origin, echocardiographic evaluation of left
ventricular structure and function (left ventricular mass and wall thickness,
compliance, and contractility) will be performed. In addition, autonomic
integrity will be assessed during a standardized battery of tests (supine rest,
paced respiration, Valsalva maneuver, lying-to standing, and sustained
handgrip); baroreceptor sensitivity and alpha- and beta-adrenoceptor
sensitivity will he tested using adrenoceptor pharmacologic challenge
(phenylephrine, isoproterenol). To determine orthostatic susceptibility, a 70
head-up tilt (HUT) test combined with beta-adrenoceptor infusion at 2 mug/min
(and then again at 5 mug/min, if the previous HUT failed to induce orthostatic
hypotension) will be performed. We will further examine the treatment effect on
exertional fatigue and hemodynamic and autonomic physiologic response to the
HUT tests. Finally, the relation between the criterion (orthostatic hypotension
susceptibility) and the predictors (hemodynamic, autonomic, cardiac
structure/function and baroreceptor, alpha-adrenoceptor and beta-adrenoceptor
sensitivities) will be evaluated to determine the extent to which the
predictors are mediating the treatment effects on orthostatic hypotension
Effective start/end date9/27/007/31/05


  • National Heart, Lung, and Blood Institute: $448,946.00
  • National Heart, Lung, and Blood Institute: $438,977.00
  • National Heart, Lung, and Blood Institute: $475,828.00
  • National Heart, Lung, and Blood Institute: $462,188.00


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.