Counterpoint: In health and in a normoxic environment, V̇ o 2 max is not limited primarily by cardiac output and locomotor muscle blood flow
2006; American Physiological Society; Volume: 100; Issue: 2 Linguagem: Inglês
10.1152/japplphysiol.01395a.2005
ISSN8750-7587
Autores Tópico(s)Blood Pressure and Hypertension Studies
ResumoPOINT-COUNTERPOINTCounterpoint: In health and in a normoxic environment, V̇o2 max is not limited primarily by cardiac output and locomotor muscle blood flowPeter D. WagnerPeter D. WagnerPublished Online:01 Feb 2006https://doi.org/10.1152/japplphysiol.01395a.2005MoreSectionsPDF (138 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Let's begin this by being sure of the question we are addressing, because this topic is notorious for being easy to spin toward one's desired position by subtly changing the question. I would like to clear the deck of spin right from the start. So I will stipulate that without blood flow, V̇o2 max would be zero: Saltin 1, Wagner 0. I will also stipulate that the venerable Fick Principle, taken at its naive simplest, would tend to support my opponent: V̇o2 = Q̇×[Cao2 − Cvo2], where Q̇ is cardiac output, Cao2 is arterial, and Cvo2 mixed venous [O2].I will even argue for him, comparing Lance Armstrong or equivalent with a sedentary normal subject each at their maximal exercise capacities, V̇o2 would be about twice as high in LA (∼80 vs. ∼40 ml·kg−1·min−1). Cao2 in the absence of erythropoietin would be close to 20 ml/dl in each, maybe even lower in LA if he shows exercise-induced desaturation (1) plus the plasma volume expansion, common in trained athletes, that results in a reduced [Hb] (16). Cvo2 would be lower in LA, perhaps as low as 2 ml/dl (i.e., 90% extraction) (5), whereas in his unfit couch potato (CP) counterpart, maximal extraction might not exceed 70% (12), with Cvo2 therefore at 6 ml/dl. Thus in the Fick equation above, maximal [Cao2 − Cvo2] approximates 180 ml/l in LA and 140 ml/l in CP. This, in turn implies that LA's peak Q̇ must be 32 l/min, whereas CP's is only 20 l/min (assuming both weigh ∼70 kg). For LA, Q̇ is 60% higher but [Cao2 − Cvo2] is only 30% higher. So Bengt would be justified in saying Q̇ is the primary determinant of V̇o2 max if the question is "what primarily explains the difference in V̇o2 max between CP and LA? Q̇ or [Cao2 − Cvo2]?" Saltin 1.5, Wagner 0. (I will return to LA and CP later. Bengt, watch out.)But, this is not the question that we are being asked to address. The question is: "Is cardiac output (or muscle blood flow) the primary determinant of V̇o2 max or not?" Stated in other words, if a normal subject is exercising at V̇o2 max and you were somehow able to augment any single part of the O2 transport and use chain, what effect would this have on V̇o2 max? And, would cardiac output, as one part of that chain, have the largest effect, as Bengt will argue? I hope he will not try and argue Q̇ is the sole limiting factor, or I will blow him out of the water in rebuttal.There is undeniable evidence that V̇o2 max can be acutely altered at will in normal humans by any one of a number of interventions (8, 10, 14, 17, 21), of which altering Q̇ is but one. Let's step down the O2 transport pathway, examining each step in turn.Changing FiO2 changes V̇o2 max in the same direction (5, 6). Ventilation at V̇o2 max is very hard to alter in normal subjects, but published theoretical models demonstrate that maximal O2 transport and thus V̇o2 max would be affected by changes in ventilation (20). V̇a/Q̇ inequality (2), alveolar-capillary diffusion limitation (18), and (post) pulmonary shunts (2) can and do play a small but demonstrable role in reducing arterial oxygenation and thus V̇o2 max, as our own editor showed many years ago (9). Cardiac output (or muscle blood flow) clearly affects V̇o2 max, although direct interventions to test this have been done only in animals such as dogs, for example, by pericardiectomy (3), which allows a higher cardiac output and V̇o2 max. Changes in [Hb] (15) and in the P50 of Hb (4, 11) both alter convective O2 transport to the muscles and have been shown to affect V̇o2 max in controlled studies. Skeletal muscle O2 transport conductance (between capillaries and mitochondria), which relates closely to capillarity, has also been shown to play a significant role in setting V̇o2 max (13). Finally, maximal mitochondrial rate of O2 consumption has the power to affect V̇o2 max (7).Although the above demonstrates, beyond argument even by Bengt, that Q̇ is by no means the only factor contributing to V̇o2 max, I have not yet provided the key arguments that must address the core question of sensitivity of V̇o2 max to a given percent change in each of the above steps. Saltin still 1.5, Wagner still 0. Answering that question will put the nail in the Q̇/Saltin coffin, as follows.First, suppose maximal mitochondrial O2 consumption is less than maximal O2 available by transport from the air to the mitochondria. Further raising O2 transport by increasing cardiac output (or for that matter any of the other above O2 pathway steps) will have no effect on V̇o2 max because it is by definition O2 supply independent. Saltin 1.5, Wagner 1.0.But suppose things are turned the other way around: maximal mitochondrial O2 use potential now exceeds O2 availability. Then, according to the evidence presented above, augmenting each and every step in O2 transport should have a positive effect on V̇o2 max, and it does. Suppose each component is augmented by 20% of its value, one at a time. Integrated physiological models incorporating all pathway steps (20) and Fig. 1 show that a 20% increase in FiO2 raises V̇o2 max by only 5.0%, due to the flat O2-Hb dissociation curve in the normal range. Increasing ventilation 20% will also lead to a small (1.3%) increase, again because Po2 is on the flat part of the curve, and raising Po2 has little effect on Cao2. Increase lung diffusing capacity 20% in an athlete who has mild hypoxemia due to diffusion limitation and V̇o2 max will increase by 2.9%. Increasing diffusing capacity in a subject without diffusion limitation obviously cannot improve V̇o2 max. If skeletal muscle O2 diffusional conductance is increased by 20%, V̇o2 max will be 5.0% higher. Increase [Hb] by 20% and V̇o2 max increases by only 3.9%. Finally, increase Q̇ by 20%, and V̇o2 max increases by only 2.6%, half that when muscle O2 conductance is raised equally. Why? Because muscle O2 conductance has only one significant effect—to increase O2 flux from blood to cells. But raising Q̇ has opposing effects (19). First, it increases convective O2 transport by the circulation as predicted by both Bengt and the Fick principle. But the higher Q̇ simultaneously reduces transit time in both lung and muscle capillaries and this worsens diffusion limitation, significantly opposing this convective gain.This brings me back to LA and CP as promised. If LA did not have a superior muscle O2 conductance to facilitate O2 transport to cells, the 32 l/min Q̇ would simply limit O2 extraction due to rapid red cell transit. The only way LA can get to 80 ml/min V̇o2 max is by having both an exceptional Q̇ and a matching, exceptional muscle capillary-to-mitochondrion O2 transport system to permit almost full O2 extraction from the rapidly flowing blood. Thus, even if Bengt argues from the Fick Principle, as in my opening paragraph, the untold story is that muscle O2 conductance must also be extraordinary, every bit as important as Q̇, or O2 extraction could not possible reach 90%. I rest my case, Bengt: Saltin 1.5, Wagner 10. Fig. 1.Calculated effects of individual changes in key O2 transport variables on V̇o2 max. Data reflect typical normal sea level values. Calculations use the model are described in Ref. 20. Note that all variables affect V̇o2, and that Q̇t is by no means the most important factor.Download figureDownload PowerPointREFERENCES1 Dempsey JA, Hanson PG, and Henderson KS. Exercise-induced arterial hypoxemia in healthy human subjects at sea level. J Physiol 355: 161–175, 1984.Crossref | PubMed | ISI | Google Scholar2 Gledhill N, Froese AB, and Dempsey JA. Ventilation to perfusion distribution during exercise in health. In: Muscular Exercise and the Lung, edited by Dempsey JA and Reed CE. 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Med Sci Sports Exerc 14: 253–262, 1982.Crossref | PubMed | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited BySensitivity of V̇O2max, critical power and V̇O2 on-kinetics to O2 concentration/delivery and other factors in skeletal muscleRespiratory Physiology & Neurobiology, Vol. 307The Oxygen Uptake Plateau—A Critical Review of the Frequently Misunderstood Phenomenon29 April 2021 | Sports Medicine, Vol. 51, No. 9Power Reserve at Intolerance in Ramp-Incremental Exercise Is Dependent on Incrementation Rate17 February 2021 | Medicine & Science in Sports & Exercise, Vol. 53, No. 8Exercise physiologyContribution of oxygen extraction fraction to maximal oxygen uptake in healthy young men30 May 2020 | Acta Physiologica, Vol. 230, No. 2The Coupling of Internal and External Gas Exchange During ExerciseMetabolic Transitions and Muscle Metabolic Stability: Effects of Exercise TrainingAn integrated view on the oxygenation responses to incremental exercise at the brain, the locomotor and respiratory muscles9 September 2016 | European Journal of Applied Physiology, Vol. 116, No. 11-12No reserve in isokinetic cycling power at intolerance during ramp incremental exercise in endurance-trained menCarrie Ferguson, Lindsey A. 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