AltitudeOmics: Resetting of Cerebrovascular CO2 Reactivity Following Acclimatization to High Altitude

Abstract

Previous studies reported enhanced cerebrovascular CO2 reactivity upon ascent to high altitude using linear models. However, there is evidence that this response may be sigmoidal in nature. Moreover, it was speculated that these changes at high altitude are mediated by alterations in acid-base buffering. Accordingly, we reanalyzed previously published data to assess middle cerebral blood flow velocity (MCAv) responses to modified rebreathing at sea level (SL), upon ascent (ALT1) and following 16 days of acclimatization (ALT16) to 5260 m in 21 lowlanders. Using sigmoid curve fitting of the MCAv responses to CO2, we found the amplitude (95 vs. 129%, SL vs. ALT1, 95% confidence intervals (CI) [77, 112], [111, 145], respectively, P = 0.024) and the slope of the sigmoid response (4.5 vs. 7.5%/mmHg, SL vs. ALT1, 95% CIs [3.1, 5.9], [6.0, 9.0], respectively, P = 0.026) to be enhanced at ALT1, which persisted with acclimatization at ALT16 (amplitude: 177, 95% CI [139, 215], P < 0.001; slope: 10.3%/mmHg, 95% CI [8.2, 12.5], P = 0.003) compared to SL. Meanwhile, the sigmoidal response midpoint was unchanged at ALT1 (SL: 36.5 mmHg; ALT1: 35.4 mmHg, 95% CIs [34.0, 39.0], [33.1, 37.7], respectively, P = 0.982), while it was reduced by ~7 mmHg at ALT16 (28.6 mmHg, 95% CI [26.4, 30.8], P = 0.001 vs. SL), indicating leftward shift of the cerebrovascular CO2 response to a lower arterial partial pressure of CO2 (PaCO2) following acclimatization to altitude. Sigmoid fitting revealed a leftward shift in the midpoint of the cerebrovascular response curve which could not be observed with linear fitting. These findings demonstrate that there is resetting of the cerebrovascular CO2 reactivity operating point to a lower PaCO2 following acclimatization to high altitude. This cerebrovascular resetting is likely the result of an altered acid-base buffer status resulting from prolonged exposure to the severe hypocapnia associated with ventilatory acclimatization to high altitude.

Global REACH 2018: The influence of acute and chronic hypoxia on cerebral haemodynamics and related functional outcomes during cold and heat stress

“…This increased MAP sensitivity has been reported previously with acclimatisation to high altitude (Fan et al . , ; Willie et al . ).…”

“…This is largely explained by the combined effects of reduced hydrogen buffering capacity and increased cerebral perfusion pressure (Fan et al . , ; Willie et al . ).…”

“…Additionally, MAP sensitivity to perturbations was enhanced at high altitude ( P < 0.01; data not shown), similar to that reported previously at slightly higher altitudes (Fan et al . , ; Willie et al . ).…”

Specific effect of hypobaria on cerebrovascular hypercapnic responses in hypoxia

“…The present results showed a left shift in CVR sigmoid curve in HH, in line with a previous study at high altitude while breathing hyperoxic mixed gas (Fan et al, ). Many studies have evaluated the cerebrovascular reactivity to CO 2 in humans exposed to high altitude (Ainslie & Burgess, ; Fan et al, , ; Flück, Siebenmann, Keiser, Cathomen, & Lundby, ; Jansen et al, ; Jensen et al, ; Lucas et al, ; Willie et al, ). However, CVR in hypoxia remains unclear with controversial results.…”

“…If P ET CO 2 elicited the minimal and maximal values of the sigmoid shape, the midpoint would not have changed. The maximum slope of the sigmoid curve is a reasonable assumption for CO 2 sensitivity (Ainslie & Duffin, ; Fan et al, ). In a sigmoidal curve, the maximum slope is found at the inflexion point, which is also the midpoint.…”