Published Online
on April 9, 2009

A more recent version of this article appeared on June 1, 2009

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Submitted on November 25, 2008
Revised on January 13, 2009
Accepted on January 19, 2009

Transcerebral Exchange Kinetics of Nitrite and Calcitonin Gene-Related Peptide in Acute Mountain Sickness. Evidence Against Trigeminovascular Activation?

Damian M. Bailey PhD, FRSC^*; Sarah Taudorf MD; Ronan M.G. Berg MD; Lars T. Jensen MD, DMSc; Carsten Lundby PhD; Kevin A. Evans MSc; Philip E. James PhD; Bente K. Pedersen MD, DMSc; and Kirsten Moller MD, PhD, DMSc

From Neurovascular Research Laboratory (D.M.B., K.A.E.), Faculty of Health, Science, and Sport, University of Glamorgan, UK; Centre of Inflammation and Metabolism (S.T., R.M.G.B., B.K.P., K.M.), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark; Department of Clinical Physiology (L.T.J.), Glostrup Hospital, University of Copenhagen; Copenhagen Muscle Research Centre (C.L.), Rigshospitalet, University of Copenhagen, Denmark; Wales Heart Research Institute (P.E.J.), School of Medicine Cardiff University, UK; Departments of Cardiothoracic Anaesthesia and Intensive Care Unit 4131 (K.M.), Rigshospitalet, University of Copenhagen, Denmark.

^* To whom correspondence should be addressed. E-mail: o2radical{at}btinternet.com.

Background and Purpose—High-altitude headache is the primary symptom associated with acute mountain sickness, which may be caused by nitric oxide-mediated activation of the trigeminovascular system. Therefore, the present study examined the effects of inspiratory hypoxia on the transcerebral exchange kinetics of the vasoactive molecules, nitrite (NO₂^•), and calcitonin gene-related peptide (CGRP).

Methods—Ten males were examined in normoxia and after 9-hour exposure to hypoxia (12.9% O₂). Global cerebral blood flow was measured by the Kety-Schmidt technique with paired samples obtained from the radial artery and jugular venous bulb. Plasma CGRP and NO₂^• were analyzed via radioimmunoassay and ozone-based chemiluminescence. Net cerebral exchange was calculated by the Fick principle and acute mountain sickness/headache scores assessed via clinically validated questionnaires.

Results—Hypoxia increased cerebral blood flow with a corresponding increase in acute mountain sickness and headache scores (P<0.05 vs normoxia). Hypoxia blunted the cerebral uptake of NO₂^•, whereas CGRP exchange remained unaltered. No relationships were observed between the change (hypoxia–normoxia) in cerebral NO₂^• or CGRP exchange and acute mountain sickness/headache scores (P>0.05).

Conclusion—These findings argue against sustained trigeminovascular system activation as a significant event in acute mountain sickness.

Key words: acute mountain sickness • brain • calcitonin gene-related peptide • hypoxia • gene-related peptide • nitrite

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