Specific effect of hypobaria on cerebrovascular hypercapnic responses in hypoxia

Abstract

It remains unknown whether hypobaria plays a role on cerebrovascular reactivity to CO₂ (CVR). The present study evaluated the putative effect of hypobaria on CVR and its influence on cerebral oxygen delivery (cDO₂ ) in five randomized conditions (i.e., normobaric normoxia, NN, altitude level of 440 m; hypobaric hypoxia, HH at altitude levels of 3,000 m and 5,500 m; normobaric hypoxia, NH, altitude simulation of 5,500 m; and hypobaric normoxia, HN). CVR was assessed in nine healthy participants (either students in aviation or pilots) during a hypercapnic test (i.e., 5% CO₂ ). We obtained CVR by plotting middle cerebral artery velocity versus end-tidal CO₂ pressure (P_ET CO₂ ) using a sigmoid model. Hypobaria induced an increased slope in HH (0.66 ± 0.33) compared to NH (0.35 ± 0.19) with a trend in HN (0.46 ± 0.12) compared to NN (0.23 ± 0.12, p = .069). P_ET CO₂ was decreased (22.3 ± 2.4 vs. 34.5 ± 2.8 mmHg and 19.9 ± 1.3 vs. 30.8 ± 2.2 mmHg, for HN vs. NN and HH vs. NH, respectively, p < .05) in hypobaric conditions when compared to normobaric conditions with comparable inspired oxygen pressure (141 ± 1 vs. 133 ± 3 mmHg and 74 ± 1 vs. 70 ± 2 mmHg, for NN vs. HN and NH vs. HH, respectively) During hypercapnia, cDO₂ was decreased in 5,500 m HH (p = .046), but maintained in NH when compared to NN. To conclude, CVR seems more sensitive (i.e., slope increase) in hypobaric than in normobaric conditions. Moreover, hypobaria potentially affected vasodilation reserve (i.e., MCAv autoregulation) and brain oxygen delivery during hypercapnia. These results are relevant for populations (i.e., aviation pilots; high-altitude residents as miners; mountaineers) occasionally exposed to hypobaric normoxia.

Trial registration: ClinicalTrials.gov NCT03303118.

Keywords: cerebral blood flow autoregulation; cerebral oxygen delivery; hypobaria; hypoxia.

Figure 1

A representative example of sigmoidal curves of all subjects (n = 9, i.e., in colors) with mean value (bold curve) during hypercapnic test in normobaric normoxia (NN, Dübendorf 440 m). Bold point represents midpoint

Figure 2

Mean sigmoidal curves of all subjects (n = 9): In normobaric normoxia (NN, Dübendorf 440 m); 3,000 m and 5,500 m in hypobaric hypoxia (HH) conditions. Bold point represents midpoint. *p < .05 midpoint different than NN; ^§ p < .05 midpoint different than 3,000 m; (a) p < .05 slope different between 5,500 m and NN; (b) p < .05 slope different between 3,000 m and NN. Shaded areas surrounding the sigmoid curves represent the 95% confidence interval

Figure 3

Mean sigmoidal curves of all subjects (n = 9) in: normobaric normoxia (NN); normobaric hypoxia (NH); hypobaric hypoxia (HH); and hypobaric normoxia (HN) conditions. Bold point represents midpoint. ^† p < .05 midpoint different between HH/HN and NH; *p < .05 midpoint different between HH/HN and NN; (a) p < .05 slope different between 5,500 m HH and NN; (b) p < .05 slope different between 5,500 m HH and NH; (c) p = .069 slope tend to be different between HN and NN. Shaded areas surrounding the sigmoid curves represent the 95% confidence interval

Figure 4

Cerebral oxygen delivery (cDO₂, absolute values) of all subjects (n = 9), Mean ±  SD. (a) Normobaric normoxia (NN) and hypobaric hypoxia (HH) conditions at 3,000 m and 5,500 m. (b) NN; normobaric hypoxia (NH); hypobaric hypoxia (HH), and hypobaric normoxia (HN) conditions. Left histograms represent cDO₂ baseline values, middle cDO₂ during hyperventilation, and right cDO₂ at the end of hypercapnia. ^# p < .05 for difference between baseline and hyperventilation values in all conditions; ^★ p < .05 for difference between hyperventilation and hypercapnia values in all conditions; ⁺ p = .014, ⁺ p < .05 for difference with baseline values; and *p = .046 for difference with NN during hypercapnia