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Review
. 2022 Jan 14:12:763933.
doi: 10.3389/fphys.2021.763933. eCollection 2021.

Influence of High Hemoglobin-Oxygen Affinity on Humans During Hypoxia

Kevin L Webb  1 , Paolo B Dominelli  2 , Sarah E Baker  1 , Stephen A Klassen  1   3 , Michael J Joyner  1 , Jonathon W Senefeld  1 , Chad C Wiggins  1
Affiliations
Review

Influence of High Hemoglobin-Oxygen Affinity on Humans During Hypoxia

Kevin L Webb et al. Front Physiol. .

Abstract

Humans elicit a robust series of physiological responses to maintain adequate oxygen delivery during hypoxia, including a transient reduction in hemoglobin-oxygen (Hb-O2) affinity. However, high Hb-O2 affinity has been identified as a beneficial adaptation in several species that have been exposed to high altitude for generations. The observed differences in Hb-O2 affinity between humans and species adapted to high altitude pose a central question: is higher or lower Hb-O2 affinity in humans more advantageous when O2 availability is limited? Humans with genetic mutations in hemoglobin structure resulting in high Hb-O2 affinity have shown attenuated cardiorespiratory adjustments during hypoxia both at rest and during exercise, providing unique insight into this central question. Therefore, the purpose of this review is to examine the influence of high Hb-O2 affinity during hypoxia through comparison of cardiovascular and respiratory adjustments elicited by humans with high Hb-O2 affinity compared to those with normal Hb-O2 affinity.

Keywords: VO2max (maximal oxygen uptake); altitude acclimatization; exercise; high affinity hemoglobin (Hb); high-altitude; oxygen transport.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Oxygen dissociation curve showing normal hemoglobin-O2 (Hb-O2) affinity (P50 ∼26 mmHg), high Hb-O2 affinity (P50 ∼16 mmHg), and low Hb-O2 affinity (P50 ∼32 mmHg). The P50, denoted by the dashed lines, is defined as the PO2 at which 50% of hemoglobin is saturated with O2.
FIGURE 2
FIGURE 2
Cardiorespiratory adjustments elicited during hypoxia by humans with high hemoglobin-O2 (Hb-O2) affinity (blue lines and symbols) and controls with normal Hb-O2 affinity (black lines and symbols). (A) Relationship of minute ventilation and arterial O2 saturation among humans with high Hb-O2 affinity compared to normal Hb-O2 affinity controls during progressive isocapnic hypoxia. Dashed lines represent data from Hebbel et al. (1977) where hypoxia was increased such that alveolar PO2 was lowered from 120 to 40 mmHg over ∼5 min (n = 2 humans with high Hb-O2 affinity and n = 2 humans with normal Hb-O2 affinity). Solid lines represent data from Dominelli et al. (2019) where hypoxia was increased such that end-tidal PO2 was lowered from normal room-air values to 50 mmHg over ∼12 min (n = 9 humans with high Hb-O2 affinity and n = 12 humans with normal Hb-O2 affinity). (B) Percentage increase in heart rate during progression of normoxia to hypoxia among humans with high Hb-O2 affinity compared to normal Hb-O2 affinity controls. Open symbols represent data from Hebbel et al. (1977) where heart rate was compared at an alveolar PO2 of 100 and 40 mmHg (n = 2 humans with high Hb-O2 affinity and n = 10 humans with normal Hb-O2 affinity). Filled symbols represent data from Dominelli et al. (2019) where heart rate was compared at normoxia and at an end-tidal PO2 of 50 mmHg (n = 9 humans with high Hb-O2 affinity and n = 12 humans with normal Hb-O2 affinity). Solid bars represent the average change in heart rate in both groups.
FIGURE 3
FIGURE 3
Difference in V˙O2max between normoxia and hypoxia in humans with high Hb-O2 affinity (blue symbols) (–4 ± 5% without outlier) compared to normal Hb-O2 affinity controls (black symbols) (–13 ± 6%). Open symbols represent data from Hebbel et al. (1978). The open triangle represents an outlier not included in the calculation of the mean. Closed symbols represent data from Dominelli et al. (2020). Solid bars represent the average change in V˙O2max in both groups not including the outlier with high Hb-O2 affinity. The dashed line provides a reference for no change.
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