Norepinephrine transporter inhibition prevents tilt-induced pre-syncope.
OBJECTIVE
We tested the hypothesis that pharmacological norepinephrine reuptake transporter (NET) inhibition delays the onset of head-up tilt-induced presyncope in healthy subjects.


BACKGROUND
Treatment of neurally mediated syncope is unsatisfactory. In a previous study in a small number of healthy subjects, pharmacologic NET inhibition delayed the onset of head-up tilt-induced pre-syncope.


METHODS
We combined data sets from 3 substudies comprising 51 healthy subjects without a history of syncope. In a double-blind, randomized, cross-over fashion, subjects underwent 2 head-up tilt tests, once with placebo and once with a NET inhibitor (sibutramine or reboxetine). Tilt testing was prematurely ended when pre-syncopal symptoms such as dizziness, nausea, or visual disturbances occurred together with a decrease in blood pressure and/or heart rate.


RESULTS
The mean tolerated tilt test duration was 29 +/- 2 min with placebo and 35 +/- 1 min with NET inhibition (p = 0.001). The odds ratio for premature abortion of head-up tilt testing was 0.22 (95% confidence interval 0.09 to 0.55, p < 0.001) in favor of NET inhibition. Norepinephrine reuptake transporter inhibition elicited a pressor response and increased upright heart rate.


CONCLUSIONS
In healthy subjects, NET inhibition prevents tilt-induced neurally mediated (pre)syncope. Therefore, NET inhibition may be a worthwhile target of drug intervention for larger trials in highly symptomatic patients with neurally mediated syncope.
Schroeder
Christoph
C
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany.
Birkenfeld
Andreas L
AL
Mayer
Antje F
AF
Tank
Jens
J
Diedrich
Andre
A
Luft
Friedrich C
FC
Jordan
Jens
J
D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003503:Cyclobutanes / Q000627:therapeutic use*; D004311:Double-Blind Method; D018475:Head-Down Tilt; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D011187:Posture; D000077593:Reboxetine; D013575:Syncope / Q000209:etiology* / Q000517:prevention & control*
D003503:Cyclobutanes; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D000077593:Reboxetine; C058254:sibutramine