Document Detail


Norepinephrine transporter inhibition prevents tilt-induced pre-syncope.
MedLine Citation:
PMID:  16875978     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: 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.
Authors:
Christoph Schroeder; Andreas L Birkenfeld; Antje F Mayer; Jens Tank; Andre Diedrich; Friedrich C Luft; Jens Jordan
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2006-07-12
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  48     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-31     Completed Date:  2006-08-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  516-22     Citation Subset:  AIM; IM    
Affiliation:
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Blood Pressure / drug effects
Cross-Over Studies
Cyclobutanes / therapeutic use*
Double-Blind Method
Head-Down Tilt
Heart Rate / drug effects
Humans
Morpholines / therapeutic use*
Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Posture*
Syncope / etiology*,  prevention & control*
Chemical
Reg. No./Substance:
0/Cyclobutanes; 0/Morpholines; 0/Norepinephrine Plasma Membrane Transport Proteins; 106650-56-0/sibutramine; 98769-81-4/reboxetine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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