The limitation to VO_{2 max} is central

Proposition for Debate - by Robin Horne

Contents

• Statement of the Topic
• Introduction
• Background Knowledge
• Conclusion
• Clinical Implications
• References
• Short Answer Review Questions

Statement of the Topic

The Limitation to VO_{2 Max} Is Central!

Introduction

Maximal oxygen uptake (VO_{2 max}) is defined as the highest rate of oxygen, which can be taken up and utilized by the body during severe exercise (Basset and Howley 2000).

It is frequently used as an indicator of an individual's cardiorespiratory fitness as oxygen consumption is linearly related to energy expenditure (Basset and Howley 2000). VO_{2 max} is commonly used in scientific literature to evaluate changes in maximal ability to work aerobically and in exercise prescription (Basset and Howley 2000).

To determine VO_{2 max}, incremental exercise testing is used. It is taken as the point at which oxygen uptake peaks with additional power failing to produce VO₂ gains (Lindstedt et al 1988). Secondary criteria to verify VO_{2 max} include:

1. expiratory exchange ratio > 1.15
2. blood lactate level > 8-9 mM (Duncan 1997)

It is generally expressed in ml.kg - 1.min - 1

There has been longstanding interest in identifying physiological factors that control VO_{2 max} and especially debate over whether the limitation is centrally or peripherally regulated.

Background Knowledge

In order to examine VO_{2 max} limitation an understanding of those factors affecting O₂ transport from the atmosphere to mitochondria of the muscle must be examined.

The O₂ delivery system can be viewed as including the pulmonary and cardiovascular systems. Central physiological factors, which may affect VO_{2 max} limitation include:

1. pulmonary diffusing capacity,
2. maximal cardiac output,
3. O₂ carrying capacity of the blood.

Peripheral skeletal muscle limitations include:

1. peripheral diffusion gradients,
2. mitochondrial enzyme levels,
3. capillary density.

Centrally Limited VO_{2 max} - Traditional View

Hill who postulated that developed the concept of maximal oxygen uptake:

1. Oxygen uptake had an upper limit;
2. VO_{2 max} was limited by the rate at which the cardiorespiratory system could transport O₂ to the muscles

(Bassett and Howley 2000)

The majority of the following research supports the concept that VO_{2 max} is limited by the rate of oxygen delivery (central factors) not the ability of the muscles to take up O₂ (peripheral factors).

Pulmonary System

The ability of the pulmonary system to maintain arterial oxygen level (% SaO₂) in healthy subjects remains high even during maximal work. Richardson et al (2000) examined whether the quadriceps are O₂ supply dependant at maximal exercise. The VO_{2 max} of the muscle group was measured during altered inspired O₂ levels (hypoxia 12%; normoxia 21% and hyperoxia 100%). It was found VO_{2 max} increased with increased O₂ delivery. It was concluded therefore that in normal conditions of isolated knee extension, VO_{2 max} of trained subjects was limited not by peripheral factors but centrally by O₂ supply.

A similar study examining the effects of breathing hyperoxic gas on the VO_{2 max} of trained athletes again demonstrated an increase in VO_{2 max} (Powers 1989).

The rationale for the increase in VO_{2 max} while breathing hypoxic gas is thought to be due to an expended arterial-venous O₂ difference (a-v O₂ difference). Small increases in hemoglobin (Hb) saturation and in O₂ dissolved in plasma produce an increased O₂ supply. Such an increase in arterial PO₂ can produce a 10% improvement in VO_{2 max} (McArdle1986).

Daniels and Oldridge (1970) likewise found that the reduced oxygen levels at altitude compared to sea level reduced maximal aerobic power in elite athletes.

These research studies demonstrate that a central pulmonary limitation to maximal exercise capacity indeed exists.

Maximal Cardiac Output

Cardiac output (CO) is determined by heart rate and the quantity of blood ejected with each stroke (stroke volume).

Hill identified maximal cardiac output as the principle factor for individual differences in VO_{2 max}. As maximal heart rates do not show considerate variation in those of a similar age, differences in VO_{2 max} have been closely related to maximal stroke volumes (Basset and Howley 2000, Bergh et al 2000).

McArdle et al (1986) conducted a study which compared maximal heart rate, stroke volume, cardiac output and VO_{2 max} among three groups; athletes, sedentary subjects and subjects with mitral valve stenosis. While maximal heart rates were similar, CO was considerably higher in the athletes due to larger stroke volumes. Those with mitral stenosis had the lowest stroke volumes. Athletes had a 62.5% higher VO_{2 max} than sedatory subjects, which paralleled a 60% higher stroke volume. Similar results were found in a study in which sedatory students put on an 8 week aerobic training program demonstrated a 35% increase in stroke volume and a similar increase in cardiac output (McArdle et al 1986).

Such research suggests a linear relationship between oxygen consumption and cardiac output over a wide range of submaximal exercise (McArdle et al 1986).

Saltin and Strange (1992) again in comparing subjects post bed rest and training found the higher VO_{2 max} post training to be due to differences in cardiac output.

Since there is little O₂ left to be extracted from venous blood in maximal exercise the main mechanism to increase VO_{2 max} with training is due to increased CO. An estimated 70-85% of the limitation to VO_{2 max} is centrally linked to maximal cardiac output (Basset and Howley 2000).

Oxygen Carrying Capacity

The hemoglobin concentration in blood alters its O₂ carrying capacity. There is again evidence to show that by manipulating this part of the O₂ delivery system, VO_{2 max} is affected. One example occurs in a low Hb environment, such as anaemia. In this situation there is a linear fall in VO_{2 max} as a function of lower Hb (Lindstedt 1988).

The practice of blood doping involves artificially increasing the Hb level by removing, storing and later infusing total red blood cells. This can increase Hb levels by 8-20%. This increases O₂ carrying capacity and produces an increase in cardiac output, by increased blood volume. A review of well-designed double blind experiments on blood doping reported VO₂ max improvements of 4-9% (McArdle et al 1986, Bassett and Howley 2000). This again strengthens the evidence that increasing O₂ delivery improves VO_{2 max}.

Periphally Limited VO_{2 max}

Skeletal Muscle Limitation

While the large body evidence presented so far would suggest a central limitation to VO_{2 max} there is research to suggest peripheral factors may also play a role. These mechanisms include peripheral diffusion gradients, mitochondrial enzyme levels and capillary density (Cain 1995, Basset and Howley 2000).

Peripheral Diffusion Gradient

Some researchers would suggest that while central mechanisms are altered to meet the needs of the peripheral system, it is the peripheral diffusion gradient, which may be the limiting factor.

The main resistance to O₂ diffusion is at the capillary sarcolemma interface. A study which used canine muscle to examine the effect of experimentally manipulating the peripheral O₂ perfusion gradient found a low intracellular PO₂ was required relative to blood PO₂ to maintain differsion and enhance conductance. When comparing the VO_{2 max} in hyperoxic breathing alone and in with the presence of a drug, which enhanced peripheral O₂, diffusion found no significant difference between the two. The conclusion drawn was again that it is not the supply of O₂ to the muscle rather than the ability of the muscle to conduct O₂ that limits VO_{2 max} (Grassi 2000). A study by Salin et al (Basset and Howley 2000) compared VO_{2 max} and cycle training. When comparing a trained leg, control leg and 2 legged bicycling VO_{2 max} was found to be 23% higher in the trained compared to the control. They concluded peripheral factors limited VO_{2 max}. They later demonstrated that this experiment was limited in using only small muscle mass as the blood flow to quadriceps was 2.3 times higher than in whole body exercise. The final conclusion drawn was that it was the increased blood flow and resultant O₂ delivery which constrained VO_{2 max} and not O₂ consumption by the muscle.

Richardson (2000) also suggests maximal metabolic rate may be set not by the mitochondrial enzyme rate but by the convective/diffusive components of O₂.

It was found PO₂ was a determination of VO_{2 max} as increased inspired oxygen levels increased intracellular PO₂. In hyperoxia the intracellular PO₂ was now in excess of mitochondrial capacity indicating cellular metabolism, which was moving towards a change between O₂ supply and O₂ demand as the VO_{2 max} limiting factor. The previous study by Grassi (2000) would indicate these findings to be due to the increased O₂ supply rather than a peripheral one.

Mitochondrial Enzyme levels

Mitochondria are located within muscle fibres and are the sites of O₂ consumption via the electron transport chain. Much research has been performed to examine whether mitochondrial enzyme levels are a limiting factor for VO_{2 max}.

Under normal circumstances oxygen uptake is matched by the demand of the mitochondria (Lindstedt et al 1988). Aerobic training causes mitochondria to enlarge and increase in number. Enhanced concentration of rate limiting enzymes also occurs, which improve the muscles capacity for aerobic production of ATP (McArdle et al, 1986).

Saltin and Strange (1992) found that even a 220% increase in mitochondrial enzymes only demonstrated a modest VO_{2 max} increase (20-40%). It is argued that the increased mitochondrial enzymes produced by aerobic training have a metabolic role in fat oxidation and to produce less lactate. Therefore the increased enzyme activity appears to be to improve endurance performance rather than increase VO_{2 max}.

Capillary Density

Training produces an increase in capillary density and this increases the capillary to muscle fibre ratio and improves O₂ extraction. This is represented as the difference between the oxygen content of arterial and venous blood (a — v O₂ difference). At rest only 5 ml of O₂ in blood is extracted from each 20 ml in 100 ml of blood, leaving 75% still bound to haemoglobin. McArdle (1986) found following 8 weeks of training subjects a-v O₂ difference was increased by 11% with 85% of O₂ extracted from blood during exercise. Saltin and Strange (1992) also show a strong relationship between capillary fibre ratio in vastus lateralis and VO_{2 max} during cycling.

It could be suggested this represented improved peripheral factors previously limiting VO_{2 max}. It is suggested however that this training effect improves O₂ delivery by enhancing mean transit time to maintain or expand O₂ extraction (a-v O₂ difference) even at high blood flow rates. This again suggests a central O₂ delivery limitation not a peripheral one.

Conclusion

There is undeniable scientific evidence to support the conclusion that it is the ability of the cardiorespiratory system to deliver O₂ to the muscles and not the ability of the mitochondria to consume O₂ that is the limitation to VO_{2 max}. This relates to healthy subjects performing maximal, large muscle mass exercise (Saltin and Strange 1992; Basset and Howley 2000; Richardson 2000).

Basset and Howley (2000) identify maximal cardiac output as the major factor limiting VO_{2 max} during bicycling and running tests. There is no single central limiting factor to VO_{2 max}. Just as O₂ delivery involves an integrated pathway, any factor which reduces the delivery of O₂ to the mitochondria, will limit VO_{2 max} (Basset and Howley 2000; Richardson 2000).

Clinical Implications

If indeed the limitation to VO_{2 max} is in the delivery of O₂ how can this knowledge be utilised to increase an individual’s capacity for aerobic work? It should be noted that endurance is not only limited by VO_{2 max} but also by factors such as lactate threshold and the efficient use of the three energy systems.

Aerobic Training

Aerobic training was found to improve O₂ delivery by increasing stroke volume and thus cardiac output by 50-60% above resting in trained athletes.

Improved a-v O₂ difference is achieved by an increased mitochondria size and number, increased rate limiting enzymes and capillary density (Basset and Howley 2000).

An 8 week training program using large muscle mass could produce a 35% increase in VO_{2 max} (McArdle et al 1986)

O₂ inhalation

There was not found to be any ergonomic value in breathing O₂ pre or post exercise with regard to improving VO_{2 max} or in increased removal of blood lactate (McArdle et al 1986).

Anaemia

As Hb levels affect O₂ carrying capacity an anaemic state can significantly affect the aerobic capacity of an individual. Early detection and correction is therefore vital.

Blood Doping

An endurance athlete who won gold at 1976 Montreal Olympics was alleged to have used this illegal technique. While there is conflicting evidence blood doping while generally thought to increase VO_{2 max} by 5-13%, reduced sub maximal HR and blood lactate levels for standard tasks and improved endurance performance at altitude and at sea level. It poses serious side effects however including venous thrombosis and pulmonary embolism via increased platelet viscosity. (McArdle et al 1986)

Respiratory and Cardiac Disease

Both respiratory and cardiac disease alter O₂ supply to working muscle and will alter an individuals ability to work aerobically. Such conditions and those taking medication, which may alter cardiac or respiratory function, must be identified by those prescribing exercise programmes.

References

Bassett DR and Howley ET (2000)

Limiting factors for maximum oxygen uptake and determinants of endurance performance. Medicine and Science in Sports and Exercise 32:70-84.

Bergh U, Ekblom B, Astrand P (2000)

Maximal oxygen uptake "classical" versus "contemporary" viewpoints. Medicine and Science in Sports and Exercise 32:85-88

Cain SM (1995)

Mechanisms which control VO₂ near VO_{2 max}: an overview. Medicine and Science in Sports and Exercise 27 (1):60-64.

Daniels J and Oldridge N (1970)

The effects of alternate exposure to altitude and sea level on world class and middle distance runners. Medicine and Science in Sports and Exercise 2:107-112.

Grassi B (2000)

Skeletal muscle VO₂ on-kinetics: set by O₂ delivery or by O₂ utilization? New insights into an old issue. Medicine and Science in Sports and Exercise 32:108-115.

Lindstedt SL, Wells DL, Jones JH, Hopprter H and Thronson HA (1988)

Limitations to aerobic performance in mammals: interaction of structure and demand. International Journal of Sports and Medicine 9:210-217.

McArdle WD, Katch FI and Katch VL (1986)

Exercise Physiology. (2^nd ed.). Philadelphia: Lea and Febiger.

Powers SK, Lawler J, Dempsey JA, Dodd S and Landry G (1989)

Effects of incomplete gas exchange on VO_{2 max}. Journal of Applied Physiology 66:2491-2495.

Richardson RS (2000)

What governs skeletal muscle VO_{2 max}? New evidence. Medicine and Science in Sports and Exercise 32:100-107.

Richardson RS, Harms CR, Grassi B and Hepple RT (2000)

Medicine and Science in Sports and Exercise 32:89-93

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.

Wagner PD (1995)

Muscle O₂ transport and O₂ Dependent control of metabolism. Medicine and Science in Sports and Exercise 27 (1):47-53.

Short Answer Review Questions

1. Explain which components of the pulmonary system may limit VO_{2 max} and
2. why.
3. Explain the mechanism by which cardiac output affects individuals VO_{2 max}?
4. Identify physiological factors which alter with training and explain how
5. they affect VO_{2 max}.
6. Identify peripheral factors which have been identified as possible limiting
7. factors to VO_{2 max}.
8. Why does anemia lower an individual's potential VO_{2 max}?

Exercise Physiology Educational Resources 2000