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The limitation to VO2 max is central!

Proposition for Debate - by Alison Low and Carolee Hatch

Statement of the Topic
Affirmative Argument by Alison Low
Negative Argument by Carolee Hatch

Statement of the Topic

The limitation to VO_{2 max} is central!

Affirmative Argument by Alison Low

Introduction

V0_{2 max} is traditionally defined as the maximal rate at which the body consumes oxygen during each minute of exercise (Basset and Howley 1997, Seiler 1996). As oxygen consumption is linearly related to energy expenditure it is therefore an indirect calculation of an individuals' maximal ability to work aerobically (Seiler 1996). High level aerobic capacity or endurance is a product of three physiological factors; a high VO_{2 max}, a high lactate threshold and the efficient use of the three energy systems. Consequently as athletes strive to push endurance to its limits there has been a great body of research performed into what limits VO_{2 max} and how it can be improved.

VO_{2 max} is determined by incremental exercise testing, and is the point at which oxygen uptake reaches a peak and additional power production fails to elicit further gains in VO₂ (Lindstedt et al 1988). The concept of VO_{2 max} can be attributed to Archibald Vivian Hill who won a Nobel Prize in 1922 for his work in the area. After conducting, in his own words, "many careful and elegant experiments on exercising man" he concluded that VO_{2 max} was limited by the capacity of the cardiovascular and respiratory systems to transport oxygen (Basset and Howley 1997). This is exactly the viewpoint of the debate today, that the limitation to VO_{2
max} is central and the negative speaker is challenged to dispute the findings of a Nobel Prize winner!

There are several elements in the oxygen transport pathway from mouth to mitochondria that have the individual potential to limit oxygen supply and therefore VO_{2 max} (Wagner 1995). These structures (in order) are pulmonary diffusion capacity, cardiac output and therefore muscle blood flow, haemoglobin concentration and diffusional transport of oxygen between muscle microcirculatory red cells and mitochondria (Wagner 1995). For the purposes of this debate all structure and functions that occur outside the perimysium will be considered as driven by central mechanisms, as maximal VO₂ and blood flow are inextricably linked (Cain 1995). Each of these structures will now be examined separately and it will be proved that the limitation to VO_{2 max} is centrally driven.

Pulmonary System

The lung can increase pulmonary surface area (and hence diffusing capacity for oxygen) in response to an increase in oxygen demand. This has been determined in the laboratory with the increase in demand for oxygen created artificially in animals through genetics, drugs and manipulation of temperature. Similarly it has been demonstrated that humans who are native to the Andes have relatively large lungs (Lindstedt et al 1988). These observations demonstrate a consistent response of an increase in diffusing capacity for oxygen to a chronic reduction in oxygen supply. If the lung does not limit VO_{2 max} (i.e. there is already more lung structure than is necessary to meet demand), it is valid to ask why does the diffusing capacity for oxygen increase in response to oxygen demand?Therefore available lung structure has been postulated to limit VO_{2 max}, however in reality this is most likely to only occur at altitude.

There have been a number of studies that have measured the response of VO_{2 max} to hyperoxic and hypoxic situations. It would appear that the reduction in VO_{2 max} in response to hypoxia is much more significant than the increase demonstrated in hyperoxia (Basset and Howley 1997,Wagner 1995). These effects closely mimic the oxygen-haemoglobin dissociation curve (fig 1). During high PO₂ there are only moderate increases in haemoglobin saturation as haemoglobin are close to maximal capacity (flat part of the curve), whereas during low PO₂ there are sharp decreases in heamoglobin saturation in response to lower levels of inspired oxygen (steep part of the curve).

Fig 1 (from McArdle, Katch and Katch 1986)

The exception to this situation has been demonstrated by Powers et al (cited in Wagner 1995) who increased inspired PO₂ in elite endurance athletes. In this group of subjects VO_{2 max} was increased by breathing higher levels of oxygen, as this corrected an arterial hypoxaemia induced by intense exercise. The phenomenon of arterial hypoxaemia was seen in the 70-80 ml/min/kg VO_{2 max} range, which according to Frontera and Adams (1986) places an individual in a 'world class runner' category. Consequently the results of this study were very impressive as already high VO_{2 max} values were pushed even higher. It is postulated that this phenomenon occurs because of the decreased transit time of the RBC's in the pulmonary capillaries of elite athletes resulting in a pulmonary diffusion limitation (Basset and Howley 1997, Frontera and Adams 1988). This provides greater evidence that pulmonary diffusing capacity can limit VO_{2 max}, particularly in the elite athlete.

Lastly it has been proposed by Wagner (cited in Ranson 1997) that the pulmonary system may limit the VO_{2 max} of elite athletes by way of CO₂ poisoning. In the average person PCO₂ fall toward VO_{2 max} suggesting that there are expiratory flow limitations. However in elite athletes CO₂ levels actually rise as VO₂ reaches its maximum secondary to their greater capacity to utilise oxygen, and potentially CO₂ may limit VO_{2 max}.

Cardiovascular System

Although there is some support in the literature for pulmonary diffusion capacity being the principal limitation to VO_{2 max}, the prevailing opinion is that VO_{2 max} is primarily limited by cardiac function. Evidence in support of this comes from experimental manipulation of haemoglobin (Hb) concentration, cardiac output and partial pressure of oxygen in arterial blood (PaO₂) (Lindstedt 1988). It has been shown that in anaemia, VO_{2 max} drops as a linear function of Hb, with similar responses demonstrated by subjecting humans to conditions whereby the Hb is preferentially bound to CO (Lindstedt 1988). More compelling evidence is generated by studies, which directly manipulate RBC's within the blood stream. It has been found that reinfusion of stored blood leads to a significant increase in VO_{2
max}, with a proportional decrease in VO_{2 max} demonstrated if RBC's are withdrawn (Poole and Richardson 1997). This raises another question to the negative speaker; if VO_{2 max} was driven by the rate of mitochondrial utililisation of oxygen there should always be a circulating supply of surplus oxygen. Consequently if oxygen supply levels were reduced by way of limiting the carrier cells (as in the aforementioned experiment) it would be reasonable to expect very little reduction in VO_{2 max}.

Cardiac output has been manipulated in a number of studies. Perhaps the most well known method of augmenting cardiac output is 'blood doping'. Oxygen delivery has also been enhanced in pericardectomised dogs (Wagner et al cited in Poole and Richardson 1997). This procedure split the pericardium of dogs to allow 20% increases in ventricular volume. The research demonstrated that in the absence of any peripheral training effect that this procedure facilitated an increased stroke volume, cardiac output and thus VO_{2 max} during maximal exercise.

Just as diffusion of oxygen through the lungs may limit oxygen uptake so might the diffusion between the capillaries and the mitochondria (Lindstedt 1988). Wagner and colleagues (cited in Lindstedt 1988) have presented evidence implicating a limitation to oxygen flow at the level of tissue diffusing capacity. They postulated that at low capillary PaO₂ there might not be adequate driving force for oxygen to diffuse to the mitochondria. If the mitochondria were hypoxic they would consequently suffer a reduction in oxygen consumption. The negative speaker may argue that this mechanism is a good example of peripheral limitation to VO_{2 max}, however capillary PaO₂ is governed by the cardiovascular system and they are therefore inextricably linked.

Oxygen Delivery

From the evidence presented thus far it would seem that the limitation to VO_{2 max} might not be a single factor, but a combination of a number of elements of the cardiopulmonary systems. Further evidence supporting this concept is generated by studies investigating the concept that it is O₂ delivery not utilisation that remains the limiting factor. A number of studies have examined the effects of active muscle mass (and hence oxygen utilisation) on VO_{2 max}. In general these researchers have found that VO_{2
max} for combined leg and arm work was similar to that elicited by legwork alone (Basset and Howley 1997). This poses the question that if limitation to VO_{2 max} was generated peripherally as the negative speaker would have you believe, why are values of VO_{2 max} for exercise that involves both arm and leg work not greater than those generated by leg work alone?

In 1979 Secher and colleagues (cited in Basset and Howley 1997) had subjects cycle for 10 minutes at 68% of VO_{2 max}, they then added arm cranking whilst continuing to maintain power output with the legs. The added arm work led to a reduction in leg blood flow and oxygen uptake with no change in mean arterial pressure. They concluded that the blood flow to the exercising legs became limited by vasoconstriction once another large muscle mass was activated. They postulate that this mechanism occurred in order for the cardiac output to maintain blood pressure and it provides further support for central limitation of VO_{2 max}.

Recently, investigators have designed the human-knee extensor model to aid in the study of metabolic capacity of human muscle (Anderson et al cited in Poole and Richardson 1997). This model allows for the measurement of blood flow, VO₂ and work rate in a functionally isolated muscle group. Data obtained from this exercise model have led to the conclusion that the small muscle mass of the quadriceps (˜2.5kg) can achieve a very high perfusion to muscle mass ratio that can exceed 3.9L/kg/min. These values were compared with peak mass specific blood flows of 1.5L/kg/min found during conventional cycling. Inspired hyperoxia did not alter these flows, which provides strong evidence that when a small muscle mass is used cardiac out put can easily meet muscular needs and therefore limitation to VO_{2 max} can not be on a peripheral level.

Conclusion

Three different research approaches have been taken to investigate the limitation to VO_{2 max}. These three aspects were; the manipulation of inspired PO₂, the manipulation of circulating PaO₂ and the manipulation of muscle perfusion. It is highly unlikely that all of the studies quoted are incorrect in their assumption that the limitation to VO_{2 max} is central, therefore the logical conclusion is to agree with this assumption.

Response to Statements by the Negative Speaker

The negative speaker has introduced some interesting points, and it may be conceded that the transport of blood to exercising muscle is indeed part of the peripheral mechanism of limitation to VO_{2 max}, however the circulating blood is inextricably linked to the central mechanisms that drive it (Cain 1995). Furthermore the author agrees that the limitation to VO_{2 max} is multifactorial, however the factors that drive this limitation are central. The negative speaker has demonstrated that mitochondrial density is proportional to VO_{2 max} and hence it is mitochondrial activity that limits oxygen consumption. This conclusion is not the only one that may be made from this observation, for it could equally be that gains in central oxygen delivery facilitate increases in mitochondria. Another point raised was that subjects with metabolic deficiencies (such as McArdle's disease) have a low a-VO₂ difference and this is what leads to their correspondingly low VO_{2 max}, this example is surely too simplistic as many factors may lead to a poor VO_{2 max} in these patients.

To conclude, the majority of data presented in today's debate points to oxygen supply (and not oxygen utilisation at a peripheral level) as the broad process that sets VO_{2 max} for an individual, under a given set of conditions. Therefore it can clearly be stated that the limitation to VO_{2 max} (and thus aerobic capacity) is central. This has been demonstrated in numerous ways:

The lung will increase in size in response to chronic low PO₂.
Manipulation of inspired oxygen will alter an individuals VO_{2 max}, hyperoxia increases VO_{2 max} and hypoxia will decrease VO_{2 max}.
Elite athletes will demonstrate a rise in CO₂ towards VO_{2 max}, which may lead to limitation by way of CO₂ poisoning.
Increasing Hb levels and/or CO will lead to a corresponding increase in VO_{2 max}.
Low capillary PO₂ may limit the diffusing capacity of O₂ to the mitochondria at a tissue level.
There is no difference between VO_{2 max} during cycling and cycling with arm cranking.
If muscles are exercised individually they have a great capacity for perfusion which is not demonstrated during exercise large muscle mass.

Short Answer Review Questions

How can the pulmonary system limit VO_{2 max}?
What would create the greatest alteration in VO_{2 max}: increasing or decreasing PO₂? How does the oxyhaemoglobin curve affect this?
How does the cardiac system limit VO_{2 max}?
Explain another way of investigating the limitation to VO_{2 max}, other than altering inspired gases of altering cardiac function (i.e. cardiac output and haemoglobin levels).

References

Basset DR and Howley ET (1997): maximal oxygen uptake: "classical" versus "contemporary" viewpoints. Medicine and Science in Sport and Exercise 29:591-603.
Cain SM (1995): Mechanisms which control VO₂ nearVO_{2 max}: an overview. Medicine and Science in Sport and Exercise 27:60-64.
Frontera WR and Adams RP (1986): Endurance exercise: normal physiology and limitations imposed by pathological processes (part 1). Physician and Sports Medicine 14:95-105.
Lindstedt SL, Wells DJ, Jones JH, Hoppeler H and Thronsen Jr HA (1988): Limitations to aerobic performance in mammals: interaction of structure and demand. International Journal of Sports Medicine 9:210-217.
McArdle WD, Katch FI and Katch VL(1986): Exercise Physiology. (2nd Ed.) Philadelphia: Lea and Febiger.
Poole DC and Richardson RS (1997): Determinants of oxygen uptake: implications for exercise testing. Sports Medicine 24:308-320.
Ranson C (1997): Limitation to VO₂. URL http://physiotherapy.curtin.edu.au/resources/educational-resources/exphys/97/limit.cfm: accessed 3 October 1998. Perth: Curtin University of Technology.
Seiler S (1996): Exercise physiology: The methods and mechanisms underlying performance. URL http://home.hia.no/~stephens/exphys.htm accessed 3 October 1998.
Wagner PD (1995): Muscle O₂ transport and O₂ dependent control of metabolism. Medicine and Science in Sport and Exercise 27:47-53.

Negative Argument by Carolee Hatch

Introduction

The limit to VO_{2 max} is central?.........or is it?

For some years there has been debate over whether the factors limiting VO_{2 max} are central or peripheral or a combination of both. Central factors limiting VO_{2 max} are thought to be the oxygen provided to the tissues as a result of pulmonary ventilation (to achieve oxygen into the blood) and cardiac output (the mechansim providing oxygen availability to the working muscles). Peripheral mechanisms are thought to be oxygen perfusion of muscle, oxygen diffusion and uptake by the mitochondria (Cain 1995).

Contemporary Viewpoints:

Contemporary viewpoints on factors limiting VO_{2 max} appear to point to multifactorial mechanisms including both central and peripheral mechanisms (Cain 1995).

The theory of symmorphosis preposes that central mechanisms are alterred in order to meet the needs of the peripheral system, that is oxygen requirements of a specific muscle mass comprising a certain number of mitochondria, impose a demand on the respiratory system and cardiac output which correspond by increasing proportional output. What is know however is that cardiac ouput reaches a point where it can no longer meet the demands of the exercising muscle and for this reason cardiac output has been regarded as one of the main mechanisms limiting VO_{2 max} (Saltin and Strange, 1992). What has not been considered by supporters of this theory however is what is happening at a muscular level at the point of VO_{2 max}. As central mechanisms are reaching their limit it may be that the mitochondrial ability to extract and process oxygen may have been exceeded which may limit further oxygen uptake. The rate at which mitochondria can use oxygen is set at 5ml O₂ per cm of mitochondria per minute. Muscle with many mitochondria (high aerobic power) will therefore be able to uptake large amounts of oxygen resulting in a large arteriovenous oxygen difference (Lindstedt et al 1988).

Some might argue that increasing oxygen consumption to the mitochondria results in greater VO_{2 max} and therefore the mitochondria are not the limiting factor. Indeed under artificially induced hyperoxia, the mitochondrial enzymes are able to respond by uptaking and processing more oxygen. Under normal circumstances however it is the mitochondria density and activity is matched with haemaglobin and oxygen availability and therefore the uptake of oxygen matches the demand of the mitochondria (Lindstedt et al 1988).

Aerobic training is known to increase the number of mitochondria in active muscle and increase ability to uptake oxygen proportionately that is mitochondrial density in the muscle is proportional to VO_{2 max}. In addition altitude and hypoxic training has been found to increase oxidative muscle enzymes (Boning 1997). Further supporting the limiting role of the mitochondria are the finding of low VO₂ in persons with muscle metabolic diseases including McArdle's disease - myophosphorylase deficiency and PFK (phosphofructokinase) deficiency. In such diseases the ability of the mitochondria to extract oxygen from the muscle capillary is altered and arteriovenous difference is low (Bassett and Howley 1997).

Perfusion of muscle or conductance of oxygen to the active muscle is another peripheral mechanisms which may limit VO_{2 max}. Evidence of perfusion limiting VO_{2 max} is the finding that exercise of a single muscle group (the knee extensors) versus mutiple groups (as in cycle ergometry) results in a disproportionately high ability to extract oxygen for the single muscle group. This limitation may be seen as central limitation of cardiac output however it is possibly the competition for peripheral perfusion (or distribution of the cardiac ouput) that limits the VO_{2 max} in the mutiple muscle task (Lindsted et al 1988).

Robergs et al (1997), exercised individuals under hypobaric hypoxic conditions to determine the effect on VO_{2 max}. The authors found that males with large lean body masses and low lactate threshold experienced the greater decriments in VO_{2 max} than individuals with small lean body mass and high lactate threshold when compared with normoxic VO_{2 max}. Such a finding may represent that greater competiton for perfusion across a greater muscle mass may occur when oxygen availability is low. Peripheral perfusion may thus be a limiting factor in this situation. The finding that low lactate threshold resulted in larger decrements in VO_{2 max} under hypoxic versus normoxic situations may represent the limitation imposed on VO_{2 max} by low oxidative capacity of the muscle or low density of mitochondria.

Aerobic training is known to increase capillary density to exercising muscle which may explain why training increases VO_{2 max}. Training also reduces shunting of blood to non active muscle which may reduce competition for peripheral perfusion thereby increasing available oxygen (Poole and Richardson 1997).

Arterial pressures of oxygen in elite athletes are often lower than in untrained subjects. This may result from red blood cells spending less time in the pulmonary capillary resulting in less time to bind with oxygen diffusing across the pulmonary membrane.

Haemaglobin concentration in athletes may also be lower as a result of expanded plasma volume which may lower conduction of oxygen to the muscles. Interestingly studies of anaemic individuals and individuals with artificially enhanced erythrocyte populations have been used to explain central mechanisms controlling VO_{2 max} (Lindstedt et al 1988).

Wagner 1995 investigated the effect of presenting the same muscle with oxygen at high and low pressure to determine the effect of diffusion from capillary to mitochondria on maximal oxygen uptake. Wagner found that reducing pressure of oxygen reduced maximum VO₂ and muscle venous and mean capillary PO₂. Such a finding highlight the effect of oxygen diffusion on VO_{2 max}.

The theory of a respiratory limitation to VO₂ max is negated by the finding that pulmonary diffusion and airway conductivity cannot adapt significantly to training. Increases in the resistance of the airways and changes in lung volumes may not alter VO_{2 max}. Evidence supporting this theory is the finding that VO_{2 max} between smokers and nonsmokers are not significantly different whilst lung volume and function in the smoking group are significantly lower than the nonsmoking group (Lindstedt et al 1988).

Whilst the pumonary diffusing capacity is essentially fixed changes in cardiac output, capillary density and muscle mitochondrial volume can all be alterred to increase VO_{2 max} (Bassett and Howley, 1997).

Lindstedt et al (1988)postulate that the highly tuned athlete has no one single factor limiting maximal oxygen consumption. Rather changes in the muscle requirements for oxygen impose demands on the cardiac ouput, peripheral perfusion, mitochondria and diffusion across the capillary/mitochondrian junction which collectively produce maximal levels of VO₂. Therefore changes to any of these factors may result in alterations in VO_{2 max}.

References

Bassett DR and Howley ET (1997): Maximal oxygen uptake: classical versus contemporary viewpoints. Medicine and Science in Sports and Exercise 29 (5):591-603.
Boning (1997): Altitude and hypoxia training: A short review. International Journal of Sports Medicine 18(8):565-70.
Cain SM (1995): Mechanisms which control VO₂ near VO_{2 max}: an overview. Medicine and Science in Sports and Exercise 27(1):60-64.
Lindedt SL, Wells DJ, Jones JH, Hoppeter H and Thronson HA (1988): Limitations to aerobic performance in mammals: interaction of structure and demand. International Journal of Sports Medicine 9:210-217.
Robergs RA, Quintana R, Parker DL, Frankel CC (1988): Multiple variables explain the variability in the decrement in VO_{2 max} during hypobaric hypoxia. Medicine and Science in Sports and Exercise 30(6):869-79.
Saltin B and Strange S (1992): Maximal oxygen uptake: "old" and "new" arguments for a cardiovascular limitation. Medicine and Science in Sports and Exercise 24:30-37.
Poole DC and Richardson (1997): Determinants of oxygen uptake: Implications for exercise testing. Sports Medicine 24(5):308-320.
Wagner PD (1995): Muscle O₂ transport and O₂ dependent control of metabolism. Medicine and Science in Sports and Exercise 27(1):47-53.