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). 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). Readers are invited to give their views on this and the accompanying CrossTalk articles in this issue by submitting a brief (250 word) comment. Comments may be submitted up to 6 weeks after publication of the article, at which point the discussion will close and the CrossTalk authors will be invited to submit a ‘Last Word’. Please email your comment, including a title and a declaration of interest to jphysiol@physoc.org. Comments will be moderated and accepted comments will be published online only as ‘supporting information’ to the original debate articles once discussion has closed. Disclaimer: Supplementary materials have been peer-reviewed but not copyedited. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. None declared.