Acute Mountain Sickness Following Incremental Trekking to High Altitude: Correlation With Plasma Vascular Endothelial Growth Factor Levels and the Possible Effects of Dexamethasone and Acclimatization Following Re-exposure

Craig Winter; Tracy Bjorkman; Stephanie Miller; Paul Nichols; John Cardinal; Peter O'Rourke; Emma Ballard; Fatima Nasrallah; Viktor Vegh

doi:10.3389/fphys.2021.746044

Acute Mountain Sickness Following Incremental Trekking to High Altitude: Correlation With Plasma Vascular Endothelial Growth Factor Levels and the Possible Effects of Dexamethasone and Acclimatization Following Re-exposure

Front Physiol. 2021 Oct 21:12:746044. doi: 10.3389/fphys.2021.746044. eCollection 2021.

Authors

Craig Winter^{1

2

3}, Tracy Bjorkman², Stephanie Miller², Paul Nichols^{1

2}, John Cardinal⁴, Peter O'Rourke⁵, Emma Ballard⁵, Fatima Nasrallah⁶, Viktor Vegh^{7

8}

Affiliations

¹ Kenneth Jamieson Department of Neurosurgery, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
² UQ Center for Clinical Research, University of Queensland, Brisbane, QLD, Australia.
³ School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD, Australia.
⁴ School of Human Movement Studies, University of Queensland, Brisbane, QLD, Australia.
⁵ Queensland Institute of Medical Research, Brisbane, QLD, Australia.
⁶ Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
⁷ Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
⁸ ARC Training Centre for Innovation in Biomedical Imaging Technology, Brisbane, QLD, Australia.

Abstract

Purpose: The recognition and treatment of high-altitude illness (HAI) is increasingly important in global emergency medicine. High altitude related hypobaric hypoxia can lead to acute mountain sickness (AMS), which may relate to increased expression of vascular endothelial growth factor (VEGF), and subsequent blood-brain barrier (BBB) compromise. This study aimed to establish the relationship between AMS and changes in plasma VEGF levels during a high-altitude ascent. VEGF level changes with dexamethasone, a commonly used AMS medication, may provide additional insight into AMS. Methods: Twelve healthy volunteers ascended Mt Fuji (3,700 m) and blood samples were obtained at distinct altitudes for VEGF analysis. Oxygen saturation (SPO2) measurements were also documented at the same time-point. Six out of the 12 study participants were prescribed dexamethasone for a second ascent performed 48 h later, and blood was again collected to establish VEGF levels. Results: Four key VEGF observations could be made based on the data collected: (i) the baseline VEGF levels between the two ascents trended upwards; (ii) those deemed to have AMS in the first ascent had increased VEGF levels (23.8-30.3 pg/ml), which decreased otherwise (23.8-30.3 pg/ml); (iii) first ascent AMS participants had higher VEGF level variability for the second ascent, and similar to those not treated with dexamethasone; and (iv) for the second ascent dexamethasone participants had similar VEGF levels to non-AMS first ascent participants, and the variability was lower than for first ascent AMS and non-dexamethasone participants. SPO2 changes were unremarkable, other than reducing by around 5% irrespective of whether measurement was taken for the first or second ascent. Conclusion: First ascent findings suggest a hallmark of AMS could be elevated VEGF levels. The lack of an exercise-induced VEGF level change strengthened the notion that elevated plasma VEGF was brain-derived, and related to AMS.

Keywords: VEGF; acclimatization; acute mountain sickness; blood-brain barrier; dexamethasone.