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Front. Physiol. | doi: 10.3389/fphys.2018.01691

Neurovascular Coupling Remains Intact During Incremental Ascent to High Altitude (4240m) in Acclimatized Healthy Volunteers

 Jack K. Leacy1, 2,  Shaelynn M. Zouboules1, Carli R. Mann1, Joel D. Peltonen1,  Gurkan Saran1, Cassandra E. Nysten1, Heidi E. Nysten3, Tom D. Brutsaert4,  Ken D. O'Halloran2, Mingma T. Sherpa5 and  Trevor A. Day1*
  • 1Mount Royal University, Canada
  • 2University College Cork, Ireland
  • 3Red Deer Regional Hospital, Canada
  • 4Syracuse University, United States
  • 5Kunde Hospital, Nepal

Neurovascular coupling (NVC) is the temporal link between neuronal metabolic activity and regional cerebral blood flow, supporting adequate delivery of nutrients. Exposure to high altitude (HA) imposes several stressors, including hypoxia and hypocapnia, which modulate cerebrovascular tone in an antagonistic fashion. Whether these contrasting stressors and subsequent adaptations affect NVC during incremental ascent to HA is unclear. The aim of this study was to assess whether incremental ascent to HA influences the NVC response. Given that cerebral blood flow (CBF) is sensitive to changes in arterial blood gases, in particular PaCO2, we hypothesized that the vasoconstrictive effect of hypocapnia during ascent would decrease the NVC response. 10 healthy study participants (21.7±1.3yrs, 23.57±2.00kg/m2, mean±SD) were recruited as part of a research expedition to HA in the Nepal Himalaya. Resting posterior cerebral artery velocity (PCAv), arterial blood gases (PaO2, SaO2, PaCO2, [HCO3-], base excess and arterial blood pH) and NVC response of the PCA were measured at four pre-determined locations: Calgary/Kathmandu (1045/1400m, control), Namche (3440m), Deboche (3820m) and Pheriche (4240m). PCAv was measured using transcranial Doppler ultrasound. Arterial blood draws were taken from the radial artery and analyzed using a portable blood gas/electrolyte analyzer. NVC was determined in response to visual stimulation (VS; Strobe light; 6Hz; 30sec on/off x 3 trials). The NVC response was averaged across three VS trials at each location. PaO2, SaO2 and PaCO2 were each significantly decreased at 3440m, 3820m and 4240m. No significant differences were found for pH at HA (P>0.05) due to significant reductions in [HCO3-] (P<0.043). As expected, incremental ascent to HA induced a state of hypoxic hypocapnia, whereas normal arterial pH was maintained due to renal compensation. NVC was quantified as the delta (∆) PCAv from baseline for mean PCAv, peak PCAv and total area under the curve (∆PCAv tAUC) during VS. No significant differences were found for ∆mean, ∆peak or ∆PCAv tAUC between locations (P>0.05). NVC remains remarkably intact during incremental ascent to HA in healthy acclimatized individuals. Despite the array of superimposed stressors associated with ascent to HA, CBF and NVC regulation may be preserved coincident with arterial pH maintenance during acclimatization.

Keywords: Neurovascular coupling., Hypocapnia, hypoxia, High-altitude (HA), cerebral blood flow

Received: 04 Sep 2018; Accepted: 09 Nov 2018.

Edited by:

Ovidiu C. Baltatu, Anhembi Morumbi University - Laureate International Universities, Brazil

Reviewed by:

Anusha Mishra, Oregon Health & Science University, United States
Bernhard Rosengarten, Klinikum Chemnitz, Germany  

Copyright: © 2018 Leacy, Zouboules, Mann, Peltonen, Saran, Nysten, Nysten, Brutsaert, O'Halloran, Sherpa and Day. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Trevor A. Day, Mount Royal University, Calgary, T3E 6K6, Alberta, Canada,