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Norepinephrine Transporter Inhibition Prevents Tilt-Induced Pre-Syncope

Christoph Schroeder, MD^_*, Andreas L. Birkenfeld, MD^_*, Antje F. Mayer^_*, Jens Tank, MD^_*, Andre Diedrich, MD, PhD, Friedrich C. Luft, MD^_* and Jens Jordan, MD^_*,_*

^_* Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany
Autonomic Dysfunction Service, Vanderbilt University, Nashville, Tennessee.

View larger version (15K): [in a new window]   Figure 1 Individual differences in tolerated time during head-up tilt testing between norepinephrine reuptake transporter (NET) inhibition and placebo treatment. In subjects who tolerated the full duration of the tilt study, both on placebo and during NET inhibition, the difference is 0. The solid vertical lines indicate the mean value and the boundaries of the 95% confidence interval.

View larger version (18K): [in a new window]   Figure 2 Kaplan-Meier plots for "tilt-test survival" with placebo (broken lines) and norepinephrine reuptake transporter (NET) inhibition (solid lines) for all 3 studies separately.

View larger version (13K): [in a new window]   Figure 3 Individual data of blood pressure and heart rate in (pre)syncopal patients on norepinephrine reuptake transporter (NET) inhibition and on placebo immediately before tilt testing had to be aborted. bpm = beats/min.

View larger version (28K): [in a new window]   Figure 4 Original beat-by-beat tracings of finger blood pressure (BP) (upper tracings) and heart rate (HR) (lower tracings) in a representative subject on placebo (left) and on norepinephrine reuptake transporter (NET) inhibition with reboxetine (right). On placebo, the patient experienced a typical neurally mediated pre-syncope with a sudden decrease in HR and BP after 24 min of head-up tilt (asterisk). On NET inhibition, upright HR was markedly increased. The subject was able to complete the tilt protocol (42 min) without pre-syncope. bpm = beats/min.