FW: RBC Mass, Autonomic Nervous System Integrity & Syncope Susceptibility in Chronic Fatigue Syndrome

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RBC Mass, Autonomic Nervous System Integrity & Syncope Susceptibility in

Chronic Fatigue Syndrome

Barry Hurwitz, Ph.D., Principal Investigator

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 physiological 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 pharmaco-therapy to expand RBC

mass; specifically, two CFS groups with low RBC mass (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 a- and b-adrenoceptor sensitivity

will be tested using adrenoceptor pharmacological challenge (phenylephrine,

isoproterenol). To determine orthostatic susceptibility, a 70° head-up tilt

(HUT) test combined with b-adrenergic agonist infusion at 2 mg/min (and then

again at 5 mg/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 physiological

response to the HUT tests. Finally, the relation between the criterion

(orthostatic hypotension susceptibility) and the predictors (hemodynamic,

autonomic, cardiac structure/function and baroreceptor, a-adrenoceptor and

b-adrenoceptor sensitivities) will be evaluated to determine the extent to

which the predictors are mediating the treatment effects on orthostatic

hypotension susceptibility.

http://www.bmrc.miami.edu/research/niaid/procrit.asp

For more information, download the brochure.

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To check for eligibility, download and open the interview form.

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