From the Clinical Research Center, Franz Volhard Clinic, Berlin, Germany
(J.J.); and the Nathan Blaser Shy-Drager Research Program, Autonomic
Dysfunction Center, Vanderbilt University, Nashville, Tenn (J.J., J.R.S.,
B.K.B., S.Y.P., J.B., D.R.).
Correspondence to David Robertson, MD, Autonomic Dysfunction Center, AA3228 MCN, Vanderbilt University, Nashville, TN 37232-2195. E-mail david.robertson{at}mcmail.vanderbilt.edu
Abstract—Patients with
idiopathic orthostatic intolerance (IOI) exhibit symptoms
suggestive of cerebral hypoperfusion and an excessive decrease in
cerebral blood flow associated with standing despite sustained systemic
blood pressure. In 9 patients (8 women and 1 man aged 22 to 48 years)
with IOI, we tested the hypothesis that volume loading (2000 cc normal
saline) and
© 1998 American Heart Association, Inc.
Scientific Contributions
Raised Cerebrovascular Resistance in Idiopathic Orthostatic Intolerance
Evidence for Sympathetic Vasoconstriction
-adrenoreceptor agonism improve systemic
hemodynamics and cerebral perfusion and that the
decrease in cerebral blood flow with head-up tilt (HUT) could be
attenuated by -adrenoreceptor blockade with
phentolamine. At 5 minutes of HUT, volume loading (-20±3.2
bpm) and phenylephrine (-18±3.4 bpm) significantly
reduced upright heart rate compared with placebo; the effect was
diminished at the end of HUT. Phentolamine substantially
increased upright heart rate at 5 minutes (20±3.7 bpm) and at the end
of HUT (14±5 bpm). With placebo, mean cerebral blood flow velocity
decreased by 33±6% at the end of HUT. This decrease in cerebral blood
flow with HUT was attenuated by all 3 interventions. We conclude that
in patients with IOI, HUT causes a substantial decrease in
cerebrovascular blood flow velocity. The decrease in blood flow
velocity with HUT can be attenuated with interventions that improve
systemic hemodynamics and therefore decrease reflex
sympathetic activation. Moreover, -adrenoreceptor
blockade also blunts the decrease in cerebral blood flow with HUT but
at the price of deteriorated systemic hemodynamics.
These observations may suggest that in patients with IOI, excessive
sympathetic activity contributes to the paradoxical decrease in
cerebral blood flow with upright posture.
Key Words: cerebral blood flow • receptors, adrenergic • phentolamine • phenylephrine • intolerance, orthostatic • tachycardia
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