Rebuttal from Carsten Lundby and David Montero

Our opponent warrants the regulation of by diffusion of O₂ from microvessels into active muscle fibres on the authority of two selected observations based on experiments conducted in isolated canine gastrocnemius preparations (Wagner, 2015). Of these observations only one is de facto, however (see below), and has already been rebutted by the bulk of canine evidence on this topic, which in line with unequivocal data in healthy humans does not indicate any regulatory role for O₂ diffusion from microvessels into muscle at (Lundby & Montero, 2015). In fact Wagner (2015) omits that his own cited work demonstrates identical muscle O₂ uptake despite having elevated P₅₀ experimentally (Richardson et al. 1998).

In humans, as legitimate evidence of O₂ diffusion limitation from microvessels into muscle at , our opponent provides an estimate of capillary O₂ pressure () simply calculated using femoral venous O₂ pressure () (Wagner, 1992, 2015; Richardson et al. 1995):

Again, this deduction has previously been rebutted according to the authors’ acknowledgement that ‘assumptions of this calculation are: the only explanation of O₂ remaining in the femoral venous blood is diffusion limitation of O₂ efflux from the muscle microcirculation. Perfusion/ heterogeneity, and perfusional or diffusio-nal shunt are considered negligible…[although these] can produce similar results’ (Richardson et al. 1995). That negligence, currently unwarranted (Koga et al. 2014; Cano et al. 2015), is precisely what may lead Wagner (2015) to interpret a three-point linear relationship between (abscissa) and (ordinate) with a negative Y-intercept as proof of O₂ diffusion limitation from microvessels into muscle (Roca et al. 1989). Conversely, the – relationship, if any, could just be indicative of complete muscle O₂ extraction in the presence of a certain degree of perfusion/ mismatch, which is reasonably suggested by the concomitant linear correlation of convective O₂ delivery and (Roca et al. 1989).

On theoretical grounds, Wagner (2015) argues on the basis of a lumped parameter of muscle O₂ diffusional conductance () that cannot be dissociated from convective O₂ delivery. This is a fundamental mathematical flaw that invalidates our opponent’s CrossTalk view.

Ultimately, the enduring efforts to authenticate that O₂ diffusion from microvessels into muscle limits/regulates merit recognition in that they have strengthened, through failure to refute, the early insights from Nobel laureate August Krogh (Krogh, 1919).

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Additional information

Competing interests

None declared.