Oxygen dissociation curve inflection point during incremental exercise: a trigger for the Bohr effect - PubMed (original) (raw)
Oxygen dissociation curve inflection point during incremental exercise: a trigger for the Bohr effect
Holger H Burchert et al. Pflugers Arch. 2025 Aug.
Abstract
We previously hypothesized that the inflection point of the oxygen dissociation curve (ODC) is linked to the gas exchange threshold (GET) during cardiopulmonary exercise testing. This hypothesis was supported by femoral venous blood gas data sampled during constant exercise below and above the GET, which showed that the ODC shifts rightward at the GET. What had gone unnoticed since these original observations in 1994 was that this rightward shift begins slightly earlier, precisely when the oxygen saturation crosses the ODC inflection point. To investigate this phenomenon, we analyzed the 1994 femoral venous blood gas data obtained during cardiopulmonary exercise testing using a modern validated mechanistic biochemical model of oxygen (O2), carbon dioxide (CO2), and proton binding to hemoglobin (Hb). We constructed the ODC for each data point, as well as the in vivo ODC-a composite curve reflecting changes in dynamic blood chemistry during exercise-to assess its alignment with the GET. The model revealed that, at the in vitro ODC inflection point (36% O2Hb saturation), the amounts of CO2 bound to Hb equalized with HbNH3+ eventually predominating. This equilibrium apparently triggered the Bohr shift, steepening the in vivo ODC to improve O2 unloading to the tissues. Shortly afterwards, the in vivo ODC reached its inflection point, matching the measured GET. Our findings support that the GET is mechanistically linked to the in vivo ODC inflection point. These results highlight the physiological relevance of determining the ODC inflection point and its alignment with HbNH3+ and CO2 binding as critical factors in understanding ODC shifts during cardiopulmonary exercise testing.
Keywords: Allosteric regulation; Anaerobic threshold; Cooperative oxygen binding; Haldane effect; Hill equation; Oxygen equilibrium curve.
© 2025. The Author(s).
Conflict of interest statement
Declarations. Competing interests: The authors did not receive support from any organization for the submitted work. The authors have no relevant financial or non-financial interests to disclose. Human ethics and consent to participate: Not applicable. Clinical trial number: Not applicable.
Figures
Fig. 1
Fig. 4B from Stringer et al. (1994) [48], adapted with permission, showing group mean femoral vein O2Hb saturation vs. PO2 during 6-min constant work rate exercise at an intensity of GET V˙O2 plus 75% of the V˙O2 difference between GET and V˙O2max. Blood was sampled at rest, every 5 s during the first 120 s of exercise (using a computer-driven anaerobic collector with time correction for dead space of the catheter), and then every 30 s for the remainder of the 6 min of exercise. Plasma pH lines were calculated using the Severinghaus model [44]. The blue line shows the sample’s pathway, while the red line marks 36% O2Hb saturation, the O2Hb saturation of the inflection point being fixed in the Severinghaus model irrespective of curve shifts [10]
Fig. 2
Redrawn Fig. 1A,D,C,B from Stringer et al. 1994 with permission [48] showing group mean femoral vein PO2, PCO2, pH, and O2Hb saturation (n = 12) from the incremental exercise testing as functions of %V˙O2max. Blood was sampled at rest, unloaded cycling, and each minute during increasing work rate exercise. Arrows mark the gas exchange threshold (GET = 64% V˙O2max). Gray shading shows 95% confidence intervals, and dashed lines indicate 95% prediction intervals
Fig. 3
A Recreated Fig. 4B from Stringer et al. 1994 incremental exercise test data (herein Fig. 1) [48]. Blue dots show O2Hb saturation vs. PO2 for n = 12 mean samples from five participants. Gray lines are the O2Hb dissociation curves calculated using the Dash et al. 2016 model with each sample’s PO2, PCO2, pH, [2,3-DPG] = 0.0029 M, Hct = 0.45, and Hb = 0.00528 M (Fig. 2) and a temperature increase from 37.0 to 38.0 °C, while the blue curve represents the in vivo O2Hb dissociation curve based on the fitted values of Fig. 2. Black dots at 50% O2Hb saturation indicate the P50 for each curve, and those around 36% mark the inflection points. CO2Hb (orange) and HbNH3+ (green) in vivo dissociation curves are plotted with the dashed gray line marking the intersection’s alignment with sample 4 passing its in vitro ODC inflection point. B Bland–Altman plot comparing the O2Hb saturation measured by Stringer et al. with the simulated ones shown in Panel A. C, D The same analyses as in panels A, B but with 37.0 °C fixed and [2,3-DPG] set to 0.00350 M
Fig. 4
Illustration of the progression of O2Hb (blue), CO2Hb (orange), and HbNH3+ (green) across the n = 12 samples, highlighting shifts in the in vitro curves and the corresponding development of the in vivo curves. Each panel presents the current sample’s data point along with its in vitro ODC, CDC, and HDC (light-colored), all previous samples’ in vitro curves (gray), and the trace of the in vivo curves as they develop from earlier data points to the present (dark-colored)
Fig. 5
The chemical species the Dash et al. 2016 model returns for the n = 12 samples of Stringer et al. 1994 and their fitted values (solid lines) as functions of %V˙O2max (Fig. 2), identifying the behavior of the equilibria of Eqs. (1) to (6). Note: The physiological parameters in the Dash et al. model vary as in the experiments of Stringer et al. (Fig. 2), capturing natural interactions among variables within the system
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