Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.
Physiol Rep. 2023 Sep;11(17):e15806. doi: 10.14814/phy2.15806.
Oxygen transport from the lungs to peripheral tissue is dependent on the affinity of hemoglobin for oxygen. Recent experimental data have suggested that the maximum human capacity for oxygen uptake and utilization (V̇O max) at sea level and altitude (~3000 m) is sensitive to alterations in hemoglobin-oxygen affinity. However, the effect of such alterations on V̇O max at extreme altitudes remains largely unknown due to the rarity of mutations affecting hemoglobin-oxygen affinity. This work uses a mathematical model that couples pulmonary oxygen uptake with systemic oxygen utilization under conditions of high metabolic demand to investigate the effect of hemoglobin-oxygen affinity on V̇O max as a function of altitude. The model includes the effects of both diffusive and convective limitations on oxygen transport. Pulmonary oxygen uptake is calculated using a spatially-distributed model that accounts for the effects of hematocrit and hemoglobin-oxygen affinity. Systemic oxygen utilization is calculated assuming Michaelis-Menten kinetics. The pulmonary and systemic model components are solved iteratively to compute predicted arterial and venous oxygen levels. Values of V̇O max are predicted for several values of hemoglobin-oxygen affinity and hemoglobin concentration based on data from humans with hemoglobin mutations. The model predicts that increased hemoglobin-oxygen affinity leads to increased V̇O max at altitudes above ~4500 m.
氧气从肺部输送到外周组织依赖于血红蛋白对氧气的亲和力。最近的实验数据表明，海平面和海拔高度 (~3000m) 下人体氧气摄取和利用的最大能力 (V̇O max) 对血红蛋白-氧气亲和力的变化敏感。然而，由于影响血红蛋白-氧气亲和力的突变很少见，因此这种变化对极高海拔 V̇O max 的影响在很大程度上仍不清楚。这项工作使用了一个数学模型，该模型将高代谢需求下的肺部氧气摄取与全身氧气利用耦合起来，以研究血红蛋白-氧气亲和力对 V̇O max 的影响作为海拔的函数。该模型包括扩散和对流限制对氧气输送的影响。肺部氧气摄取是使用一个空间分布模型计算的，该模型考虑了血细胞比容和血红蛋白-氧气亲和力的影响。全身氧气利用假设为米氏动力学。通过迭代求解肺部和全身模型组件，计算预测的动脉和静脉氧水平。根据具有血红蛋白突变的人类的数据，基于几个血红蛋白-氧气亲和力和血红蛋白浓度值来预测 V̇O max 的值。该模型预测，血红蛋白-氧气亲和力的增加会导致海拔高于约 4500m 时 V̇O max 的增加。
