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(Stroke. 2009;40:2205.)
© 2009 American Heart Association, Inc.

Research Letters

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 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.

Correspondence to Damian M. Bailey, PhD, FRSC, Neurovascular Research Laboratory, Faculty of Health, Science, and Sport, University of Glamorgan, Mid-Glamorgan, South Wales, UK, CF37 1DL. 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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