Muscle oxygenation during hypoxic exercise in humans: Effect of high‐affinity hemoglobin
Authors: Ahmed Elshaer N. , Dominelli Paolo B. , Baker Sarah E. , Shepherd John R.A. , Hoyer James D. , Oliveira Jennifer L. , Joyner Michael J. , Wiggins Chad C. 
Published: April 2020

BackgroundIn humans, maximal exercise capacity is reduced during hypoxic environmental conditions. In response to hypoxia, the hemoglobin binding affinity is decreased, promoting oxygen off‐loading at the tissue level and causing a right‐shift of the oxyhemoglobin dissociation curve (ODC). However, comparative biology demonstrates many species (e.g. Bar‐headed geese), who are adapted to hypoxia instead have high‐affinity hemoglobin (left‐shifted ODC). Therefore we studied unique human participants with hemoglobinopathies that result in high affinity hemoglobin (HAH) to investigate the role of oxygen affinity in exercise performance and tissue oxygenation during hypoxic conditions.MethodsHAH participants (n=5, 1M/4F, Age= 34±11 yr, P50=16±1 mmHg) and matched control participants (n=12, 5M/7F, age=39±12 yr, and P50=26±1 mmHg) completed two incremental exercise tests to exhaustion on a cycle ergometer under two conditions: 1) room air (FiO2= 0.21, NORM), and 2) normobaric hypoxia gas mixture (FiO2= 0.15, HYP), separated by a 45 minute break. The vastus lateralis (VL) muscle was studied using frequency‐domain near infrared spectroscopy (NIRS) to measure concentrations of oxygenated ([OxyHb+Mb]), deoxygenated ([DeoxyHb+Mb]) hemoglobin and myoglobin, and tissue saturation (StO2). Data were analyzed using a three‐way (Inspirate [HYP, NORM], Hb type [Normal, HAH], exercise intensity [Rest, 40, 60, 80, 100% normoxic PPO]) univariate analysis of variance.ResultsHAH had an attenuated decline in exercise tolerance (peak power output at maximal exertion) in HYP compared to controls (HAH: 2.9±6.4% decline vs CTL: 11.7±5.4% decline, P<0.05). There was a significant effect of Hb type on [DeoxyHb+Mb] (P=0.048) suggesting less O2 offloading in HAH compared to controls in the VL at rest and throughout graded exercise in both NORM and HYP. There were no significant effects of inspirate or exercise intensity on [DeoxyHb+Mb], and no significant differences in [OxyHb+Mb] between HAH and controls. There was a significant effect of Hb type on StO2 in NORM controls (P<0.01) However, during hypoxic exercise StO2 was the same in both HAH and controls except at end exercise (HAH 64.1±6.4% vs CTL: 62.1±4.2%, P<0.05).ConclusionHAH individuals have less oxygen off‐loading at rest and during exercise but higher tissue saturation during exercise in NORM compared to controls. Our results suggest that the similar levels of exercise capacity in hypoxia for HAH are due, at least in part, to maintenance of microvascular extraction similar to that during normoxic exercise. Future studies utilizing direct measurements of skeletal muscle blood flow during exercise are needed to understand integrative exercise in HAH patients.Support or Funding InformationThis work was funded by NIH R‐35‐HL139854 and the Mayo Foundation.Muscle oxygenation during graded exercise tests in normoxia and hypoxia. Data are presented as means ± standard error. Abbreviations: [OxyHb+Mb], concentration of oxygenated hemoglobin+myoglobin; [DeoxyHb+MB], concentration of deoxygenated hemoglobin+ myoglobin; PPO, peak power output. † denotes significant main effect of Hb types across all workloads. * denotes significant difference from CTL at same %PPO.Figure 1