Do Not Be Misled by Physiological Models,Rely on Experimental Data. The Authors Reply

Professor Böning summarizes some parts of our review (Calbet and Lundby, 2009). In contrast with what he states in the title of his letter, he actually emphasizes the importance that lung O₂ diffusion has for Vo₂max at altitude. Böning's speculations on the role attributed to venous Po₂ are a bit confusing. We assume that he is referring to mixed venous Po_2. This variable is only indirectly influencing pulmonary gas exchange and, as Böning wrote in his letter, it is the gradient between Pao₂ and the mean capillary Po₂ that establishes the driving pressure for O₂ diffusion in the lung (Dlo₂). Obviously, mean capillary Po₂ does not depend only on mixed venous Po₂. Böning states that Dlo₂ during exercise at altitude can be increased by recruiting more capillaries and increasing the erythrocyte area. We suppose that he actually means increasing the number of erythrocytes in contact with the air interphase when the blood crosses the alveolar sacs. Although the first part of his comment is correct and was actually treated in our review, the second part merits some comments. We and others have shown that increasing blood hemoglobin concentration either acutely or by altitude acclimatization or erythropoietin treatment does not increase Vo₂max or Dlo₂ at altitudes above 4000 m (Calbet and Boushel, 2009). Moreover, reducing blood hemoglobin concentration at high altitude (5260 m above sea level) did not result in lower Vo₂max (Calbet et al., 2002). However, increasing [Hb] at sea level and at moderate altitude up to 3500 m increases Vo₂max (Robach et al., 2008). Thus, the effect of [Hb] on Vo₂max depends on the position of the oxygen dissociation curve (ODC) (determined by the Pao₂, which in turn depends to a great extent on the altitude at which the exercise is performed). As far as we know, there is only one study in which the influence of altitude acclimatization at 4100 m on the ODC has been studied in lowlanders and high altitude natives by determining the changes in the in vivo P₅₀ at the levels of the lung and active muscles during exercise (Lundby et al., 2006). Moreover, blood acidification perturbs pulmonary gas exchange at Vo₂max (Calbet et al., 2009). Our experimental data do not support the belief of Bönning that an increase of [Hb] by 20% increases O₂ extraction by 20% (Calbet et al., 2006). Moreover, Böning is misleading the readers regarding the effects of [Hb] on O₂ diffusing from the red cells to the muscle mitochondria. We wrote, “In the same manner as increasing [Hb] facilitates the diffusion of O₂ from the alveolar space to the vascular space (Roughton and Forster, 1957) it could make difficult the diffusion of O₂ from the red cells to the muscle mitochondria, particularly without the in vivo rightward shift of P₅₀. However, muscle O₂ conductance (an estimation of muscle diffusing capacity) was not influenced by [Hb] during maximal exercise in chronic hypoxia” (Calbet et al., 2002). Thus it should be clear that the experimental data show that in humans exercising in hypoxia the increases and reductions of [Hb] of ∼10% to 20% have no effect on maximal exercise muscle O₂ conductance. Böning should bear in mind that mathematical models, when wrongly applied, may be misleading and that physiologists should always rely on experimental data. We tried to do this in our review.