Maximal oxygen

Comments on Point:Counterpoint: Maximal oxygen uptake is/is not limited by a central nervous system governor Roy J. Shephard

J Appl Physiol 106:343-346, 2009. doi:10.1152/japplphysiol.zdg-8326.pcpcomm.2008 You might find this additional info useful... This article cites 44 articles, 35 of which can be accessed free at: http://jap.physiology.org/content/106/1/343.full.html#ref-list-1 This article has been cited by 1 other HighWire hosted articles Last Word on Point:Counterpoint: Maximal oxygen uptake is/is not limited by a central nervous system governor Bjorn T. Ekblom J Appl Physiol 2009; 106 (1): 348. [Full Text] [PDF]

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J Appl Physiol 106: 343–346, 2009; doi:10.1152/japplphysiol.zdg-8326.pcpcomm.2008.

Point:Counterpoint Comments

Comments on Point:Counterpoint: Maximal oxygen uptake is/is not limited by a central nervous system governor HARD EVIDENCE FOR A CENTRAL GOVERNOR IS STILL LACKING! TO THE EDITOR:

REFERENCES 1. Dempsey JA, Hanson PG, Henderson KS. Exercise-induced arterial hypoxaemia in healthy human subjects at sea level. J Physiol 355: 161–175, 1984. 2. Ekblom B. Counterpoint: Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008a. 3. Hill AV, Long CHN, Lupton H. Muscular exercise, lactic acid and the supply and utilisation of oxygen: parts VII-VIII. Proc Royal Soc B 97: 155–176, 1924. 4. Noakes TD, Marino FE. Point: Maximal oxygen uptake is limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008. 5. Whyte GP. Clinical significance of cardiac damage and changes in function after exercise. Med Sci Sports Exerc 40: 1416 –1423, 2008.

Roy J. Shephard Professor Emeritus of Applied Physiology University of Toronto TO THE EDITOR: The discussion regarding Noakes’ challenge to ˙ O2max continues in the excellent Point:Counthe concept of V terpoint by Noakes and Marino (6) and Ekblom (3). It seems, however, that both are so engaged in an either/or argument that they have missed the point that perhaps Hill (5) was right, although forgivably too simplistic, over 80 years ago. Recent studies, including from our laboratory (4) have confirmed that ˙ O2 reaches values during incremental exercise, which are V rarely exceeded even when higher intensity exercise is perhttp://www. jap.org

REFERENCES 1. Amann M, Eldridge MW, Lovering AT, Stickland MK, Pegelow DF, Dempsey JA. Arterial oxygenation influences central motor output and exercise performance via effects on peripheral locomotor muscle fatigue in humans. J Physiol 575: 937–952, 2006. 2. Amann M, Romer LM, Pegelow DF, Jacques AJ, Hess CJ, Dempsey JA. The effects of arterial oxygen content upon peripheral muscle fatigue. J Appl Physiol 101: 119 –127, 2006. 3. Ekblom B. Counterpoint: Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008a. 4. Foster C, Kuffel E, Bradley N, Battista RA, Wright G, Porcari JP, ˙ O2max during successive maximal efforts. Eur Lucia A, de Koning JJ. V J Appl Physiol 102: 67–72, 2007. 5. Hill AV, Long CHN, Lupton H. Muscular exercise, lactic acid and the supply and utilisation of oxygen: parts VII-VIII. Proc Royal Soc B 97: 155–176, 1924. 6. Noakes TD, Marino FE. Maximal oxygen uptake is limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol.90844. 2008.

Carl Foster1 Alejandro Lucia2 1 Professor 2 University of Wisconsin-La Crosse NO SUPPORT FOR CENTRAL GOVERNOR TO THE EDITOR: Noakes and Marino (4) have not designed experiments that provide support for the central governor model (CGM). Moreover, they have not identified the specific components (e.g., stimuli, receptors, and afferent nerve fibers) involved in the negative feedback loop that supposedly protects the heart from overexertion. Ekblom’s (1) findings contradict the CGM of Noakes and Marino (4). Ekblom elegantly showed that when the body is ˙ O2 and Q ˙ level off, but subjected to supramaximal work rates, V EMG activity and the work of the heart continue to increase. Noakes and Marino (4) respond that since EMG activity ˙ O2max is less than during a during combined A⫹L exercise at V maximum voluntary contraction for the respective muscle groups, a central governor in the brain must be limiting skeletal

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Reviewing evidence for and against a Central Governor that limits an individual’s maximal oxygen intake (2, 4), I am impressed that although this hypothesis was formulated some 11 years ago, it still lacks support outside the proponent’s laboratory. I note also that, perhaps because of an inappropriate test protocol, Noakes has consistently found difficulty in reaching first base in this area of research, the demonstration of an oxygen consumption plateau. In contrast, Ekblom and colleagues (2) have had no problems in this regard. Noakes (4) currently argues that a Central Governor is essential to prevent the development of a dangerous myocardial ischemia. However, anyone who has exercised older adults will know that a substantial proportion of such individuals manifest myocardial ischemia. Ultraendurance athletes also develop myocardial ischemia (3), and indeed may use this as a stimulus to cardiac hypertrophy. Does this imply that ultraendurance athletes and old people have carelessly broken their Central Governors? Noakes also cites (4), with apparent approval, the argument of A. V. Hill (3) that the Governor dissuades the heart from making an excessive effort that would reduce the oxygen saturation of arterial blood. Again, the weight of current evidence is that well-motivated athletes do reduce their arterial oxygen saturations (1). Moreover, it would be hard to imagine how the mechanism postulated by Noakes could evolve, since the forces of natural selection have not focused on the ability to perform a maximal oxygen intake test.

˙ O2max is limited centrally, limitations of cardiac formed. If V output can as reasonably be attributed to limitations of venous return, diastolic filling time, and ventricular compliance as to losses of contractility secondary to the potential myocardial ischemia that Noakes correctly suggests must be avoided. It is also documented that failures to maintain saturation of haemoglobin during heavy exercise are common. Thus the concept of ˙ O2max is supportable (2) decreases in “offered O2” limiting V and may be associated with an array of outcomes including changes in the iEMG-power output ratio and stimulated muscle performance (1). Finally, as anyone who has performed an incremental exercise test knows, this leads to the compelling “I don’t want to continue” sensation. So, yes, there must be a command coming from the central nervous system that tells the exerciser that homeostasis is becoming disturbed and that it would be advisable to stop. But, many if not most, of these “stop” signals are reasonably attributable to limitations in central O2 transport and aerobic ATP generation.

Point:Counterpoint Comments 344 muscle recruitment. Although it is true that skeletal muscle recruitment during a 1- to 2-s anaerobic “burst” is greater than ˙ O2max, this does during strenuous, dynamic exercise at 100% V not show that receptors in the myocardium are sending action potentials back to a central governor in the brain, resulting in inhibition of motor units. Ekblom (1) cites strong evidence that Qmax, and not a central ˙ O2max. When the dog pericardium is governor, determines V ˙ O2max (5). In addition, other cut, Qmax increases and so does V researchers have found that whenever Qmax is diminished (through cardioselective ␤-blockade, atrial fibrillation, or mi˙ O2max (2–3, 6). Thus O2 tral stenosis), there is a decrease in V delivery and the pumping capacity of the heart are key deter˙ O2max. minants of V REFERENCES

David R. Bassett Professor, Exercise Science University of Tennessee, Knoxville ˙ O2max AND EXERCISE PERFORMANCE V TO THE EDITOR: To resolve this debate, it is necessary to clearly distinguish between what limits performance and what limits ˙ O2max during dynamic whole body exercise. When a plateau V is achieved during an incremental test, or when “supramaximal” exercise is sustained long enough (1), it is clear that ˙ O2max is limited by the factors underlying the Fick equation, V particularly stroke volume. However, it often happens that a subject decides to stop exercise before the physiological limits of the Fick equation are reached (e.g., in hypoxia). In these ˙ O2 measured is proportional to exconditions, the maximal V ercise performance, which, in turn, is limited by the brain. So both parties of this debate are right. However, we disagree with Noakes and Marino that exercise performance is subconsciously regulated by a central governor on the basis of afferent feedback from the heart and other organs. In fact, we proposed that exercise performance is regulated by the conscious brain on the basis of potential motivation (defined as the maximum effort a person is willing to exert to satisfy a motive) and perceived exertion (5) without the need for an extra central governor (2–3). There is also strong experimental evidence that perception of effort is generated by corollary discharges of central commands to the locomotor and respiratory muscles rather than afferent sensory feedback (4). The facts that many cardiac patients can exercise past the point of myocardial ischemia (as indicated by ST segment depression) and stop

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REFERENCES 1. Hill DW, Poole DC, Smith JC. The relationship between power and the time to achieve VO2max. Med Sci Sports Exerc 34: 709 –714, 2002. 2. Marcora SM. Do we really need a central governor to explain brain regulation of exercise performance? Eur J Appl Physiol 104: 929 –931, 2008. 3. Marcora S. Entia non sunt multiplicanda praeter necessitatem. J Physiol 578: 371, 2007. 4. Marcora SM. Perception of effort during exercise is independent of afferent feedback from skeletal muscles, heart, and lungs. J Appl Physiol; doi:10.1152/japplphysiol.90378.2008. 5. Marcora SM, Bosio A, de Morree HM. Locomotor muscle fatigue increases cardiorespiratory responses and reduces performance during intense cycling exercise independently from metabolic stress. Am J Physiol Regul Integr Comp Physiol 294: R874 –R883, 2008. 6. Sylve´n C, Borg G, Holmgren A, Astro¨m H. Psychophysical power functions of exercise limiting symptoms in coronary heart disease. Med Sci Sports Exerc 23: 1050 –1054, 1991.

Samuele M. Marcora Senior Lecturer in Exercise Physiology School of Sport, Health and Exercise Sciences Bangor University Wales, United Kingdom TO THE EDITOR: The lack of experimental evidence ascertaining ˙ O2max or the the contribution of the central nervous system to V exact amount of muscle mass active during exercise, makes it more fruitful to focus this passionate debate (1, 4) on testable aspects of Dr. Noakes’ central governor model (CGM), which proposes that “the brain regulates the extent of skeletal muscle recruitment to ensure that a truly maximal cardiac output is never achieved”(4). Drs. Noakes and Marino concede that, “a finding that cardiac function and skeletal muscle recruitment are both absolutely maximal and that homeostasis is lost at VO2max would disprove the CGM”(4). While we agree that skeletal muscle recruitment might not be absolutely maximal ˙ O2max, compelling evidence in during exercise eliciting V trained humans indicates that a plateau or drop in cardiac output (due to a fall in stroke volume) and blood flow to active ˙ O2max and muscles and brain precede the attainment of V exhaustion during incremental and constant maximal cycling (2, 3, 5 ,6). Importantly, cardiac output and active muscle blood flow plateau early in constant supramaximal cycling at values similar to maximal cycling, accompanying a decline in stroke volume (6). The close coupling between muscle perfusion and metabolic demand is therefore disturbed even prior to ˙ O2max, possibly because vasoconstriction limits blood flow to V muscles as cardiac function reaches its regulatory capacity (6). Thus our findings argue strongly against the CGM by supporting that the regulatory capacity of the human circulation is ˙ O2max. reached and homeostasis is lost prior to achieving V REFERENCES 1. Ekblom B. Point: Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008a. 2. Gonza´lez-Alonso J, Calbet JA. Reductions in systemic and skeletal muscle blood flow and oxygen delivery limit maximal aerobic capacity in humans. Circulation 107: 824 – 830, 2003. 3. Gonza´lez-Alonso J, Dalsgaard MK, Osada T, Volianitis S, Dawson EA, Yoshiga CC, Secher NH. Brain and central haemodynamics and oxygenation during maximal exercise in humans. J Physiol 557: 331–342, 2004.

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1. Ekblom B. Counterpoint: Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008a. 2. Kakimoto T, Yamabe H, Yokoyama M. Exercise performance after PTMC in mitral stenosis: the relation with hemodynamics, ventilatory response and skeletal muscle function. Kobe J Med Sci 42: 307–323,1996. 3. Lundstro¨m T, Karlsson O. Improved ventilatory response to exercise after cardioversion of chronic atrial fibrillation to sinus rhythm. Chest 102: 1017–1022, 1992. 4. Noakes TD, Marino FE. Point: Maximal oxygen uptake is limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008. 5. Stray-Gundersen J, Musch TA, Haidet CG, Swain DP, Ordway GA, Mitchell JH. The effect of pericardioectomi on maximal oxygen uptake and maximal cardiac output in untrained dogs. Circ Res 58: 523–530, 1986. 6. Tesch PA. Exercise performance and beta-blockade. Sports Med 2: 389 – 412, 1985.

because of chest pain (6) also argue against the model proposed by Noakes and Marino.

Point:Counterpoint Comments 345 4. Noakes TD, Marino FE. Point: Maximal oxygen uptake is limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008. 5. Mortensen SP, Damsgaard R, Dawson EA, Secher NH, Gonza´lezAlonso J. Restrictions in systemic and locomotor skeletal muscle perfusion, oxygen supply and VO2 during high-intensity whole-body exercise in humans. J Physiol 586: 2621–2635, 2008. 6. Mortensen SP, Dawson EA, Yoshiga CC, Dalsgaard MK, Damsgaard R, Secher NH, Gonza´lez-Alonso J. Limitations to systemic and locomotor limb muscle oxygen delivery and uptake during maximal exercise in humans. J Physiol 566: 273–285, 2005.

Jose Gonza´lez-Alonso1 Stefan P. Mortensen2 1 Centre for Sports Medicine and Human Performance Brunel University 2 Copenhagen Muscle Research Centre MAXIMAL OXYGEN UPTAKE REGULATION AS A BEHAVIORAL MECHANISM

REFERENCES 1. Cheung SS. Hyperthermia and voluntary exhaustion: integrating models and future challenges. Appl Physiol Nutr Metab 32: 808 – 817, 2007. 2. Ekblom B. Counterpoint: Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008. 3. Flouris AD, Cheung SS. Human conscious response to thermal input is adjusted to changes in mean body temperature. Br J Sports Med [January 23, 2008]. 4. Noakes TD, Marino FE. Point: Maximal oxygen uptake is limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008. 5. Romanovsky AA. Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system. Am J Physiol Regul Integr Comp Physiol 292: R37–R46, 2007. J Appl Physiol • VOL

Stephen S. Cheung Canada Research Chair Andreas D. Flouris Brock University EXPERIMENTAL EVIDENCE MAY INFORM THE DEBATE TO THE EDITOR: The discussion on whether a central nervous ˙ O2max) exists (1, system governor to maximal oxygen uptake (V 5) may be informed by a series of experimental animal studies that we have performed, although admittedly, they were not designed to resolve the current debate. Nonetheless, they serve a purpose here. ˙ O2max during graded treadmill runWe repeatedly measure V ning at increasing work rates. These records usually show evi˙ O2 despite increased running speeds (4). dence of a plateau of V Thus the plateau phenomenon is observed across species. More interestingly is perhaps that when we anesthetize and induce left ventricular myocardial infarctions in rats, we see ⬃40% reduced ˙ O2max and running capacity (3, 4, 6). These animals have V never been exercised before, and the procedure does not involve or affect either the skeletal muscle or the central nervous system. Instead, these studies indicate a cardiac ˙ O2max, since the pump dysfunction as the cause of reduced V rat, after all, is able to perform incremental exercise to high ˙ O2 levels off, despite the heart already being intensities until V ischemic. It is therefore difficult to see how a central nervous ˙ O2max by system command would dictate the change in V limiting skeletal muscle work in anticipation of myocardial ischemia under these conditions. Has the heart-skeletal muscle information line disentangled itself, or was it never there? Although this does not prove the non-existence of a central nervous system governor, it does put significant limitations to a model that does not include a major role of the central circulatory system.

REFERENCES 1. Ekblom B. Counterpoint: Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphsyiol. 90844.2008a. 2. Hoydal MA, Wisloff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil 14: 753–760, 2007. 3. Kemi OJ, Hoydal MA, Haram PM, Garnier A, Fortin D, VenturaClapier R, Ellingsen O. Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan. Cardiovasc Res 76: 91–99, 2007. 4. Kemi OJ, Loennechen JP, Wisloff U, Ellingsen O. Intensity-controlled treadmill running in mice: cardiac and skeletal muscle hypertrophy. J Appl Physiol 93: 1301–1309, 2002. 5. Noakes TD, Marino FE. Point: Maximal oxygen uptake is limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008. 6. Wisloff U, Loennechen JP, Currie S, Smith GL, Ellingsen O. Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility, Ca2⫹ sensitivity and SERCA-2 in rat after myocardial infarction. Cardiovasc Res 54: 162–174, 2002.

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Ole J. Kemi Assistant Professor University of Glasgow www.jap.org

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TO THE EDITOR: The Central Governor Model [CGM (4)], ˙ O2max) is limited by suggesting that maximal oxygen uptake (V a central nervous system governor, challenges the Traditional Model (TM) according to which the heart’s pumping capacity, not peripheral factors in the muscles, is the factor limiting ˙ O2max (2). From a philosophical standpoint, the CGM sugV ˙ O2max is reached as an active behavioral mechagests that V ˙ O2max represents a passive nism, while the TM holds that V limit in the system’s capacity to transform chemical energy into mechanical. On the basis of our understanding of mammalian physiology (1), CGM and TM can harmoniously coexist within a system, the former being a prescient behavioral mechanism preventing imminent myocardial ischemia by limiting peripheral blood flow, and the latter being a safety measure employed when CGM means are insufficient. This arrangement mirrors the thermoregulatory system, with behavioral responses dependent on shell temperature signals from peripheral thermosensors being deployed to prevent anticipated thermal insults (3), while autonomic and endocrine responses, based more on core temperature signals from central thermosensors, employed when body heat content changes because behavioral responses were inadequate or could not be used due to conflicting behavioral demands (5). We have shown, for instance, a centrally originating progressive impairment in neuromuscular activation, independent of local muscle temperature, occurring prior to temperature-induced system catastrophe (6). If our hypothesis is true, however, the CGM would be ˙ O2max factor, since TM would be more prevalent as a limiting V employed only prior to system collapse. This would explain the increased support that the CGM has received (4).

6. Thomas MM, Cheung SS, Elder GC, Sleivert GG. Voluntary muscle activation is impaired by core temperature rather than local muscle temperature. J Appl Physiol 100: 1361–1369, 2006.

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during exercise, since the CGM would cause “protective fatigue” reducing exercise intensity and ultimately preventing an infarct. REFERENCES 1. Amann M, Calbet JA. Convective oxygen transport and fatigue. J Appl Physiol 104: 861– 870, 2007. 2. Calbet JA, Boushel R, Radegran G, Sondergaard H, Wagner PD, Saltin B. Determinants of maximal oxygen uptake in severe acute hypoxia. Am J Physiol Regul Integr Comp Physiol 284: R291–R303, 2003. 3. Calbet JA, Gonzalez-Alonso J, Helge JW, Sondergaard H, MunchAndersen T, Boushel R, Saltin B. Cardiac output and leg and arm blood flow during incremental exercise to exhaustion on the cycle ergometer. J Appl Physiol 103: 969 –978, 2007. 4. Calbet JA, Lundby C, Sander M, Robach P, Saltin B, Boushel R. Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans. Am J Physiol Regul Integr Comp Physiol 291: R447–R453, 2006. 5. Ekblom B. Counterpoint: Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008a. 6. Noakes TD, Marino FE. Point: Maximal oxygen uptake is limited by a central nervous system governor. J Appl Physiol; doi:10.1152/japplphysiol. 90844.2008.

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Prof. Jose A. L. Calbet Carsten Lundby Educacio´n Fı´sica University of Las Palmas de Gran Canaria, Spain

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TO THE EDITOR: This is a rather unbalanced debate because it has been demonstrated with several experimental approaches that ˙ O2max is limited by oxygen delivery (5). In contrast, in health V the central governor model (CGM) is mostly supported by sophistic reasoning, used to re-elaborate some obviations. For example, if the central nervous system does not receive sufficient oxygen then a number of physiological functions will be affected (1). Maximal exercise capacity may be limited by insufficient brain oxygenation during exercise in extreme hypoxia (2). However, even in the latter situation we do not have irrefutable evidence for central mechanisms of fatigue. It is not true that the CGM impedes “to reach a truly maximal cardiac output to prevent myocardial ischemia by limiting peripheral blood flow” (6), because maximal vasodilation at peak exercise, increases cardiac output without changing peak leg blood ˙ O2max in humans (4). Actually, experimental evidence flow or V indicates that the work of the heart, i.e., the variable determining myocardial oxygen demand, increases continuously during a gradual exercise to exhaustion without signs of reaching a plateau (3). Moreover, despite the ongoing discussions regarding the need of the central governor to protect the heart by blunting central command, it has been shown that the heart can protect itself very well (without need of a CGM). If the CGM was true, and is acting to prevent myocardial ischemia, then subjects with coronary syndrome would never have angina