Tracking cerebral blood flow regulation during incremental ascent to altitude: Effect of superimposed hypoxia and hypocapnia
Authors: Lafave Hailey C , Zouboules Shaelynn , James Marina , Purdy Graeme , Rees Jordan , Ondrus Peter C , Nysten Heidi C , Brutsaert Tom C , Nysten Cassandra , Steinback Craig , Sherpa Mingma , Day Trevor 
Published: June 2021

High altitude exposure imposes a unique cerebrovascular challenge due to the presentation of two opposing blood gas stimuli. Specifically, hypoxia causes cerebral vasodilation, increasing cerebral blood flow (CBF), whereas respiratory‐induced hypocapnia causes cerebral vasoconstriction, decreasing CBF. Accordingly, arterial blood gases are large determinants of resting CBF, but the conflicting nature of these two superimposed chemostimuli presents a challenge in tracking CBF responsiveness with ascent to altitude. The extent that conflicting arterial blood gas variables affect CBF during incremental ascent to moderate altitude (i.e., the typical ascent profile for trekkers) is unclear. In 16 lowlanders during incremental ascent to altitude, we aimed to (a) characterize the relationship between arterial blood gas stimuli with regional and global CBF and (b) develop a novel index to track changes in CBF in relation to simultaneous but conflicting chemostmuli. During ascent to 4370m over seven days in the Nepal Himalaya, participants underwent serial resting measures at 1045m, 3440m (day 3) and 4370m (day 7) during incremental ascent to altitude. These measures included: arterial blood draws [radial artery; partial pressure of arterial (Pa)CO2, partial pressure of arterial (Pa)O2, arterial O2 saturation (SaO2)], unilateral anterior, unilateral posterior and global CBF (Duplex ultrasound; internal carotid artery [ICA] and vertebral artery [VA], global CBF [{ICA+VA}x2], respectively). We developed a novel stimulus index (SI), taking into account both chemostimuli (PaCO2/SaO2). Subsequently, both regional (ICA and VA) and global cerebral CBF were indexed against the SI to assess steady‐state cerebrovascular responsiveness (SS‐CVR). As expected, PaCO2, PaO2 and SaO2 all decreased with ascent to altitude (all P<0.001). SI remained relatively constant with ascent with a decrease observed at 4370m (P=0.07). Anterior (ICA) and global CBF did not increase significantly with ascent (P=0.15 and P=0.09, respectively), likely due to competing and simultaneous dilatory (hypoxia) and constricting (hypocapnia) chemostimuli. However, posterior (VA) CBF was significantly increased in comparison to baseline at 4370m (P=0.03). SS‐CVR for both regional and global CBF was significantly increased at 4370m (day 7 of altitude exposure; P<0.03) but not at 3440m (day 3 of altitude exposure; P0.08). Our data suggest that regional differences exist in CBF with incremental ascent, but that when indexed against superimposed and competing chemostimuli, SS‐CVR increases in both regional and global measures after seven days during incremental ascent to 4370m. Our novel SS‐CVR metric tracks cerebrovascular responsiveness during incremental ascent to moderate altitude, highlighting the importance of the braking effect of hypocapnia on cerebral blood flow regulation at altitude.

Support or Funding Information

This work was supported by (a) Alberta Government Student Temporary Employment Program, (b) Alberta Innovates Health Solutions Summer Studentship, and (c) Natural Sciences and Engineering Research Council of Canada Discovery grant.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.