Submitted on October 22, 2007
Accepted on January 4, 2008
NOREPINEPHRINE TRANSPORTER INHIBITION ALTERS
THE HEMODYNAMIC RESPONSE TO HYPERGRAVITATION
Sebastian Strempel1, Christoph Schroeder1, Ruth Hemmersbach2, Andrea Boese2, Jens Tank3, Andre Diedrich4, Martina Heer2, Friedrich C. Luft1, and Jens Jordan1*
1 Franz Volhard Clinical Research Center, Medical University Charite, Berlin, Germany
2 Department of Aerospace Medicine, German Aerospace Center, Cologne, Germany
3 Franz Volhard Clinical Research Center, Medical University Charite, United States; Internal Medicine, HELIOS Klinikum , Berlin, Germany
4 Department of Medicine, Division of Clinical Pharmacology, Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, Tennessee, United States
* To whom correspondence should be addressed. E-mail: jens.jordan{at}charite.de.
Background. Sympathetically-mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness (g-LOC). Norepinephrine transporter (NET) inhibition prevents neurally-mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus, it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress.
Methods. We performed a double-blind, randomized, placebo-controlled crossover study in 11 healthy men (26±1 yrs, BMI 24±1 kg/m2) who ingested the selective NET inhibitor reboxetine (4 mg) or matching placebo 25, 13, and 1 h before testing on separate days. We monitored heart rate, blood pressure, and thoracic impedance in three different body positions (supine, seated, standing) and during a graded centrifuge run (incremental steps of 0.5 g for 3 min each, up to a maximal gz-load of 3 g).
Results. NET inhibition increased supine blood pressure and heart rate. With placebo, blood pressure increased in the seated position and was well maintained during standing. However, with NET inhibition blood pressure decreased in the seated and standing position. During hypergravitation, blood pressure increased in a graded fashion with placebo. With NET inhibition, the increase in blood pressure during hypergravitation was profoundly diminished. Conversely, the tachycardic response to sitting, standing, and hypergravitation all were greatly increased with NET inhibition.
Conclusions. In contrast to our expectation, short term NET inhibition did not improve tolerance to hypergravitation. Redistribution of sympathetic activity to the heart or changes in baroreflex responses could explain the excessive tachycardia we observed.
