(Circulation. 1999;99:1706-1712.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Abnormal Norepinephrine Clearance and Adrenergic Receptor Sensitivity in Idiopathic Orthostatic Intolerance
Presented in part at the 69th Scientific Sessions of the American Heart Association and published in abstract form (Circulation. 1996;94[suppl I]:I-341).
From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.).
Correspondence to David Robertson, MD, Autonomic Dysfunction Center, AA3228 MCN, Vanderbilt University, Nashville, TN 37232-2195. E-mail david.robertson{at}mcmail.vanderbilt.edu
Background—Chronic
orthostatic intolerance (OI) is characterized by symptoms
of inadequate cerebral perfusion with standing, in the absence of
significant orthostatic hypotension. A heart rate increase
of 
30 bpm is typical. Possible underlying pathophysiologies include
hypovolemia, partial dysautonomia, or a primary hyperadrenergic state.
We tested the hypothesis that patients with OI have functional
abnormalities in autonomic neurons regulating cardiovascular
responses.
Methods and Results—Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55±5% versus 30±7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50±10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5±0.05 versus 1.0±0.1 µg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105±11 versus 210±12 µg, P<0.001). Baroreflex sensitivity was lower in patients (12±1 versus 18±2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups.
Conclusions—The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.
Key Words: norepinephrine • receptors, adrenergic, alpha • receptors, adrenergic, beta • nervous system, autonomic
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