Entries in Lactic Acid (2)


Exercise Science and Coaching: Correcting Common Misunderstandings About Endurance Exercise

By: Andrew N. Bosch, PhD
UCT/ MRC Research Unit for Exercise Science and Sports Medicine.
Department of Human Biology, University of Cape Town and Sports Science Institute of South Africa
From: International Journal of Sports Science & Coaching Volume 1 • Number 1 • 2006

Many coaches who work with endurance athletes still believe in old concepts that can no longer be considered correct. Prime amongst these are the understanding, or misunderstanding, of the concepts of maximal oxygen uptake (VO2 max), lactate threshold, training heart rate, and dehydration and fluid requirements during prolonged exercise.

Knowing the VO2 max of an athlete is not particularly useful to the coach, and the exact VO2 max value of any particular athlete can vary considerably as fitness changes. Race performance is a more useful measure on which to base training schedules.

Lactic acid production, far from being an undesirable event, is of great importance and is actually beneficial to the athlete. The lactate concentration during exercise, and the lactate turnpoint, are both widely measured. The nature of the information that these measures can provide about training and training status, however, is still based on information from the 1980s, although more current information is available and many of the original concepts have been modified.

Heart rate is often used to prescribe training intensity, but it is important to understand the limitations inherent in its use. If used correctly, it is a useful tool for the coach.
Similarly, many athletes and coaches still believe that it is necessary to maintain a high fluid intake to avoid dehydration and prevent associated collapse. These beliefs are incorrect, but modern exercise science has been able to advance the knowledge in this area and provide more accurate information.
Exercise science continues to progress and can offer much to the coach willing to accept new and changing ideas.

Key words: Anaerobic threshold; Endurance training; hydration; lactic acid; maximal oxygen uptake; training heart rate


Sports science knowledge has progressed tremendously in the last 20 years in terms of the understanding of many of the underlying concepts in exercise physiology and human performance. Many coaches, however, have failed to take cognisance of the new information and still believe in old and out-dated concepts, many of which frankly are wrong. And it is this incorrect understanding that is then applied to the coaching of athletes. In the following article, some of these misconceptions related to endurance performance are highlighted, specifically those around maximal oxygen uptake (VO2 max), lactate threshold, training heart rate, dehydration, and fluid requirements during prolonged exercise. Although runners are most often referred to in the discussion that follows, the principles are applicable to all genre of endurance athlete.

VO2 Max

Every so often a request is received from the coach of a runner or cyclist wanting to know ifit would be possible to measure the VO2 max of one of their athletes. I explain that it is, indeed, possible, but then go on to ask why they want to have the VO2 max of the athlete measured? There is usually one of two replies. Firstly, I am told, by knowing his or her VO2 max the runner will know the esoteric time that he or she is ultimately capable of running for some particular race distance, and therefore their ultimate potential as a runner. Secondly, once their VO2 max is known it will be possible to prescribe the ultimate personalised training schedule. Unfortunately, knowing the VO2 max of a runner does not answer either question.

It is widely believed by those involved in endurance sports that the VO2 max is genetically determined and never changes, and that an individual is born with either a high or low VO2 max. Generally, someone with a high VO2 max value is considered to have a cardiovascular system capable of delivering large amounts of oxygen to the working muscle and is able to exercise at a maximum aerobic work output that is determined by the exercise intensity that can be sustained by this supply of oxygen [1]. In this paradigm it does not appear to matter whether a runner or cyclist is unfit or superbly fit, the VO2 max value obtained in a test is theoretically the same. However, it is intuitively obvious that when fit, the athlete can run much faster on the treadmill than when unfit. Thus, since VO2 max is genetically determined and does not change, VO2 max would be reached at a relatively slow running speed when a runner is unfit compared to when very fit, when a much higher speed or workload can be reached. This means that in a totally unfit world class runner we would measure a high VO2 max (for example, 75 ml/kg/min or higher, a reasonable VO2 max value for an elite runner) at a speed of maybe 17 km/hr in a testing protocol in which the treadmill remains flat during the test. When very fit the same athlete will reach the same VO2 max, but now the speed reached on the treadmill will be around 24 km/hr (a reasonable speed for an elite athlete in such a test). The problem is that such a high VO2 max is never measured at a speed of just 17 km/hr, or thereabout. This would be almost impossibly inefficient [2]. The theory of a genetically set and unchanging VO2 max, regardless of work output therefore begins to appear a little shaky.

This concept of VO2 max evolved originally from misinterpretation of the data of early experimental work [1; 3-5]. It was believed that as an athlete ran faster and faster during a treadmill test, an increasing volume of oxygen was needed by the muscles, a process which continued until the supply of oxygen became limiting, or the ability of the muscle to utilise oxygen was exceeded. At this point there would be no further increase in oxygen uptake, despite further increases in running speed [1]. The plateau in oxygen utilisation was regarded as the VO2 max of the runner. If high, then the athlete had great genetic potential. This has been termed the cardiovascular/ anaerobic model by Noakes [1] and needs revision, although others adhere to the concept [6]. However, 30% of all runners and cyclists tested in exercise laboratories never show a plateau in their oxygen uptake [4; 7]. Instead, the oxygen uptake is still increasing when the athlete cannot continue the test. The conventional view of VO2 max now appears to be even more suspect.

Consider a different possibility. The muscles of a runner require a certain amount of oxygen to sustain contraction at a given speed. When the speed is increased, the muscles have to work harder and there is therefore a corresponding increase in the volume of oxygen needed to run at the higher speed. As the runner runs faster and faster, it follows that there is a concomitant increase in the oxygen required, until ultimately something other than oxygen supply to the muscle prevents the muscle from being able to work harder and to sustain a further increase in running speed.

The brain may be the ultimate subconscious controller, by sensing a pending limitation in the maximum capacity of the coronary blood flow to supply oxygen to the heart as exercise intensity increases, and then preventing a further increase in muscle contractility to prevent damage to the heart during maximal exercise [1].

The volume of oxygen being used by the muscle when maximum running speed has been reached is termed the VO2 max. With this theory, the increase in oxygen requirement merely tracks the increase in running speed, until a peak running speed and therefore peak oxygen requirement (VO2 max) is attained. It is easy to see why the VO2 max value will change (which it does) as a runner gets fitter and becomes capable of running faster. Within this framework, the genetically determined limit of VO2 max is actually determined by the highest running speed that the contractility of the muscles can sustain [8] before the brain limits performance to protect the heart, as described above [1]. Of practical importance, is that the exercise scientist and coach cannot use the VO2 max test as a predictor of future performance in someone who still has the capacity to improve their running by utilising a scientifically designed training programme. A great training-induced increase in running speed will result in a substantial change in VO2 max. Only when widely disparate groups of athletes are tested can a VO2 max value be used to distinguish between athletes (i.e. very fast and very slow [2; 9; 10]). In a group of athletes with similar ability, the VO2 max value cannot distinguish between the faster and slower runners i.e. their race performance. Neither is the knowledge of a VO2 max value going to assist in the construction of a training programme, other than by indirectly giving an indication of the time in which a race may currently be completed, by the use of various tables that are available [11]. Indeed, current race performance provides the most useful information for the coach on which to base training prescription [11].

There are, however, some potential uses of a VO2 max test for a coach. When constructing a training programme for someone who has not run any races and who therefore has no race times from which to determine current ability, a VO2 max test will help by giving an indication of the current capability of the athlete on which to base training schedules. If done at regular intervals, the test can provide information about the efficacy of a training programme [11] as laboratory conditions are very reproducible with regard to temperature and absence of wind. However, the peak speed attained in the test is probably the best indicator of current ability [1; 12-14] and not the actual VO2 max value. Race times remain the most useful measure on which to prescribe running speed in training schedules [11].

Lactic Acid

Most athletes and coaches still believe that lactic acid is released during hard or unaccustomed exercise and that this is what limits performance, as well as being the cause of stiffness. Neither is correct. Furthermore, the terminology “lactic acid,” is not correct.

Lactic acid does not exist as such in the body - it exists as lactate at physiological pH [15], and it is this that is actually measured in the blood when “lactic acid” concentration is measured, as is done when a “lactate threshold” is determined in an athlete. This distinction is important not only for the sake of correctness, but more importantly, because lactate and lactic acid would have different physiological effects.

The first misconception is that lactic acid is the cause of the stiffness felt after an event such as a marathon. Stiffness is due to damage to the muscle [1], and not an accumulation of lactic acid crystals in the muscle [1; 16], as is commonly believed.

The second misconception is that lactate is responsible for acidifying the blood, thereby causing fatigue. To the contrary, the production of lactate is actually important for two reasons. Firstly, when lactate is produced from pyruvate in the muscle, a hydrogen ion is “consumed” in the process [15]. Consequently the production of lactate actually reduces the acidity in the muscle cells and is thus a beneficial process. Secondly, lactate is an important fuel that is used by the muscles during prolonged exercise [17; 18]. It can be produced in one muscle cell and utilized as a fuel in another, or it can be released from the muscle and converted in the liver to glucose, which is then used as an energy source. So rather than cause fatigue, lactate production actually helps to delay fatigue [19].

Anaerobic Threshold

Closely allied to the thinking that lactate production is bad for performance, is the concept of measuring the blood lactate concentration to determine the so-called “anaerobic threshold” or “lactate threshold.”. The origin of this belief can probably be traced to the early studies of Fletcher and Hopkins [20]. Thus we see photographs of athletes at the track or at the side of the pool having a blood sample taken, with an accompanying caption indicating that the workout is being monitored by measuring “lactic acid.” The supposed rationale is that as speed is increased, a point is reached at which there is insufficient oxygen available to the muscle and energy sources that do not require oxygen (oxygen independent pathways, previously termed the anaerobic energy system) then contribute to the energy that is needed. This supposedly results in a disproportionate increase in the blood lactate concentration, a point identified as the “anaerobic” or “oxygen deficient” threshold. This is also known as the lactate threshold or lactate turnpoint.

There are two problems with this concept. First of all, the muscle never becomes anaerobic; there are other reasons for the increase that is measured in blood lactate concentration [21]. Secondly, the so-called disproportionate increase causing a turnpoint is not correct, in that the increase is actually exponential [22-24]. This is seen when many samples are taken, as in the exercise laboratory, where a blood sample can be drawn every 30 seconds as an athlete runs faster and faster.

Although a graph showing a “breakpoint” in lactate concentration as speed increases cannot be drawn as the breakpoint does not exist, a graph can nevertheless be drawn depicting the curvilinear increase in blood lactate concentration as running speed or exercise intensity increases. This curve changes in shape (shifts to the right) as fitness level changes. Particularly, the fitter a runner gets, the more the curve shifts to the right on the graph, meaning that at any given lactate concentration the running speed or work output is higher than before. A shift in the lactate curve to a higher workload or percentage VO2 max occurs due to a reduced rate of lactate production by the muscles and an increased ability of the body to clear the lactate produced [25; 26]. Often, the running speed at a lactate concentration of 4mmol/l is used as a standard for comparison. It is sometimes suggested that this can be used as a guide for training speed (i.e. a runner could do some runs each week at the speed corresponding to the 4mmol/l lactate concentration, some runs above this speed, and recovery runs at a lower speed). Of course, as fitness changes and the curve shifts, these speeds will change, and so a new curve will have to be determined. In concept this works well, but the problem is that neither exercise scientists nor coaches know how much running should be done below, at, and above the 4mmol/l concentration. The 4 mmol/l concentration referred to is a somewhat arbitrarily chosen concentration. It could just as well have been 3.5 mmol/l or 4.5 mmol/l, which would result in different training speeds for the athlete utilizing this system. Indeed, Borch et al [27] suggest 3 mmol/l as the lactate concentration representing an average steady state value. Measuring the maximal steady state lactate concentration may be useful, but requires 4-5 laboratory visits. Thus the real value in determining a ‘lactate curve’ is to monitor how it shifts with training. The desirable shift is one in which a faster running speed is achieved at the same lactate concentration. This regular testing can be done in the laboratory, with the athlete running on a treadmill or on a track, in which running speed can be carefully controlled, such as by means of pace lights.

Training Heart Rate

In recent years the concept of using heart rate while training as an indicator of the correct training intensity, has gained in popularity. Specifically, various heart rate “training zones” have been suggested, and ways to calculate these proposed. This approach has been described in many articles written for coaches and runners [27-29] and does have potential for being a precise way to regulate running intensity in training, particularly for novice runners. However, at present there are no scientific data to support an ideal specific heart rate for different types of training, and much of what is written is based on anecdotal experiences. There is no doubt that future studies will refine this area, making the prescription of training heart rate a more exact science.

Probably the greatest value in heart rate in training is for the coach to use it as a way of ensuring that an athlete does not train too hard on those days when nothing more than an easy training session is prescribed. The use of heart rate for more absolute prescription has the risk of the athlete training at the wrong intensity as a result of the large daily variability in heart rate due to influence of diurnal variation, temperature differences, sleep patterns, and stress [30]. All these can result in the prescribed training heart rate being either too high or too low on a given day. Thus the athlete may train too easily on one day, but on another day when more recovery is needed from a prior hard training session, the training intensity may be too high. The coach is probably better able to assess the most suitable intensity for the athlete. Nevertheless, training intensity based on heart rate may have some value [28].

The use of heart rate as a monitoring tool during training, as opposed to being used to dictate training intensity is a useful aid that coaches can use to assess the training response of an athlete. A progressive decline (over weeks) in heart rate for a given training session would indicate appropriate adaptive response by the athlete; a progressive increase in normal training heart rate would indicate a failure in the adaptive process and that the training load should be adjusted. Similarly, an abnormally high heart rate for a given training session may indicate approaching illness or failure to adapt to the training load and impending overtraining. The athlete would then be well-advised to train only lightly, or to rest [30].

Post-Run Stiffness

In the section on lactic acid, it was stated that the stiffness and muscle pain felt after a marathon or hard workout is not caused by lactic acid. While this was believed to be the case some decades ago, it is now known that lactic acid is not the cause of muscle stiffness, but is the result of damage to the muscle cells, connective tissue and contractile proteins [31-33].

Although the precise cause of delayed onset muscle soreness remains unknown, all runners and coaches are aware that the degree of pain depends on the intensity, duration and type of workout. For example, there is more muscle pain after a long or hard downhill run than after running over flat terrain (i.e. if eccentric muscle actions are emphasised [34]). In fact, it is this phenomenon that begins to exclude a build-up of lactic acid as a cause of the pain. In downhill running, the concentration of lactate in the blood and muscle will be low compared to running at the same speed on the flat. Thus, the most painful post-race stiffness can occur when the lactate concentration is lowest.

If a blood sample is taken from a runner the day after a marathon, especially an ultra- marathon, the concentration of an enzyme, creatine kinase, will be high [35-37]. This is an indication that muscle damage has occurred, as this particular enzyme “leaks” from damaged muscle. The “damage” referred to is minute tears or ruptures of the muscle fibres [38; 39]. This trauma to the muscle can be visualised if a sample of the muscle is examined microscopically. However, it is not just the muscle that is damaged. By measuring the amino acid hydroxyproline, it is possible to show that the connective tissue in and around the muscles is also disrupted [40]. What this shows is that stiffness results from muscle damage and breakdown of connective tissue.

Running fast or running downhill places greater strain on the muscle fibres and connective tissue compared with running on the flat. Downhill running is particularly damaging because of the greater eccentric muscle actions that occur. It is this simultaneous contracting of the muscle while being forced biomechanically to lengthen that is most damaging to muscle fibres.

What does this mean for the runner and coach? From a training and racing point of view, after the muscles have recovered from the damage that caused the stiffness and the adaptive process is complete, the muscle is more resistant to damage from subsequent exercise for up to six weeks [41]. From a coaching point of view, hard training sessions should be withheld when there is muscle pain, as further damage could result. It would be better to allow the appropriate physiological adaptations to take place before resuming hard training sessions. Weight training to increase the strength of the muscle [1] may be beneficial. It has been suggested that vitamin E may help to reduce muscle soreness, but there is little evidence to support this idea [42]. Vitamin E is thought to act as an antioxidant that may blunt the damaging action of free radicals, which attack the cell membrane of the muscle fibre.

It has also been suggested that stretching the painful muscle or muscles may be beneficial, but this has not consistently been shown to alleviate delayed onset muscle soreness. Neither is there any evidence that massage or ultrasound speed up recovery [43]. Similarly, an easy “loosening up” run “to flush out the lactic acid” is unlikely to speed up recovery, although it is also unlikely to result in further damage.

The real cause of muscle stiffness after a hard run is clearly not due to lactic acid in the muscle. Coaches will be in a better position to manage the return to normal training of their athletes after training or racing that has induced muscle soreness, if they understand the effects of type, intensity, and volume of training on muscle stiffness after exercise.

Dehydration, Heat Exhaustion and Heat Stroke

Historically, the understanding has been that runners collapse (most often at the end of races) due to dehydration. This is popularly thought to be more likely when the environmental temperature is high and dehydration more severe. “Heat exhaustion” has been incorrectly thought to be associated with dehydration, yet there is no evidence to support this [1]. “Heat stroke” is an entirely different condition, associated with an increase in body temperature.

There are a number of critical errors in the traditional thinking on the issue of dehydration. Firstly, and possibly most importantly, rectal temperatures are not abnormally elevated in collapsed runners suffering from “dehydration” [44; 45]. Secondly, there is no published evidence that runners with dehydration/ heat exhaustion will develop heat stroke if left untreated [46; 47]. And thirdly, the question must be asked why these runners nearly always collapse at the finish of the race and not during the race. Thus we must look for another explanation as to why the runners collapse.

The explanation is found in a condition called postural hypotension [44; 47-50]. While running, the high heart rate and rhythmic contraction of the leg muscles maintain blood pressure and aids in the return of blood from the legs. When running ceases, the pump action of the leg muscles stops and the heart rate drops rapidly. This results in pooling of the blood in the veins of the lower limb, which in turn causes blood pressure to decrease. It is the lowered blood pressure that results in collapse. Secondly, there is an increase in peripheral blood flow to regulate body temperature. This is more pronounced in hot conditions, and results in a reduction in the pressure of blood filling the heart [51]. Treatment is therefore very simple: If the runner lies down with the legs elevated, the return of blood from the legs is aided, blood pressure is restored and after a short while the runner will have recovered. Cooling the legs may be beneficial. As a preventive measure, it is a good idea to continue to walk after the finish line has been crossed. A second possibility is to lie down as soon as possible and elevate the legs slightly, with cooling of the legs as an additional option.

Heat exhaustion as a result of dehydration does not, therefore, exist and is not a condition that coaches need to be concerned about. This contrasts with heat stroke, in which the body temperature becomes very high (rectal temperature above 41°C) and is a potentially dangerous condition. Even after the athlete has stopped, either voluntarily or because of collapse, the temperature remains elevated because of physiological and biochemical abnormalities in the muscles. Thus the athlete must be cooled as quickly as possible, using methods such as fans, to bring the body temperature down to below 38 degrees Celsius.
Heat stroke develops as a result of a combination of a number of factors. Particularly, a high environmental temperature (>28°C) is more likely to result in the problem than when conditions are cooler. If the humidity is also high, there is an additional heat load on the runner because the sweating mechanism of the body is rendered ineffective. Sweat running off the body, as it does when the humidity is high, does not result in cooling. To cool the surface temperature of the skin, the sweat must evaporate. In addition, and also very importantly, the metabolic heat produced by the runner must be high. Thus, it is the faster athletes who are at risk, who are exercising at a high intensity. It is also, therefore, in races shorter than the marathon in which there is a high likelihood of heat stroke because of the much higher running intensity in shorter races such as cross country (on a hot day) or a 10 km race [46; 47; 52]. Thirdly, it appears that some runners are more susceptible to the development of heat stroke than others [53].

Contrary to popular belief, dehydration is not a major cause of the development of heat stroke. Although adequate fluid replacement during racing in the heat may reduce the risk of heat injury, it is not the only factor and may not even be the most important factor [46; 47; 54; 55]. Arunner can develop heat stroke without being dehydrated. Conversely, a runner can be dehydrated, but not develop heat stroke. If the recommended guidelines for fluid ingestion are followed (~600 ml/ hour), it is very unlikely that fluid deficit will play a role in the development of heat stroke.

Fluid Intake During Exercise

During events such as marathon running, one often reads recommendations suggesting that more than 1L of fluid should be ingested every hour. Ingestion of such a high volume is unnecessary, however, and probably impossible for faster runners to adhere to.

The rate at which fluid ingested during exercise empties from the stomach before being absorbed in the small intestine is influenced by a number of factors. These include the temperature of the fluid, the volume of fluid ingested, and the concentration of any carbohydrate such as glucose, fructose, sucrose or glucose polymer in the water. Thus it is important that athletes follow the correct regimen to ensure optimal fluid and carbohydrate replacement. This consists of ingesting 500-600 ml per hour of a fluid containing 7-10% carbohydrate [56]. This serves two purposes. It supplies a source of carbohydrate to maintain blood glucose concentration, as well as all the fluid replacement that is necessary during prolonged exercise, except possibly under extreme environmental conditions.

Ingestion of too much water during prolonged exercise is not only unnecessary, but can be harmful. In some susceptible people, ingesting large volumes of water can result in a condition called “water intoxication” or hyponatraemia. This occurs when the body’s normal sodium concentration becomes significantly diluted, because the amount of water or sports drink ingested is far in excess of what is needed during exercise to maintain hydration [46; 54; 57; 58]. As with heat stroke, in extreme cases this condition can be life threatening, in this case due to cerebral oedema.


VO2 max testing can be of some limited use to a coach when constructing a training programme for someone who has not run any races. If done regularly, the test can provide information about the efficacy of a training programme. However, the peak speed attained in the test is probably the best indicator of current ability, but race times are the most useful measure on which to prescribe running speed in training schedules.

Rather than cause fatigue, the process of lactate production helps to delay fatigue. In addition, it is important as a fuel substrate. The real value in determining a ‘lactate curve’ is to monitor how it shifts with training, the desirable shift being one in which a faster running speed is achieved at the same lactate concentration.

Heart rate during training is a useful monitoring tool, but should not be used to dictate training intensity. Rather, training heart rate information, together with knowledge of current race speeds and training-induced fatigue, should be used by the coach to determine training intensity. Ultimately, the influence of various parameters that effect heart rate response will be well researched and the coach will then be able to prescribe a specific heart rate for different types of training.

Muscle stiffness after a hard run is not due to lactic acid in the muscle. Return to normal training should be prescribed based on the knowledge that soreness is due to muscle damage.

Dehydration is not a major cause of the development of heat stroke. Heat stroke can occur without dehydration, and conversely, dehydration can occur without heat stroke. If the recommended guidelines for fluid ingestion are followed, it is very unlikely that fluid deficit will play a role in the development of heat stroke.

Ingestion of too much water during prolonged exercise is not only unnecessary, but can be harmful. In some susceptible people, ingesting large volumes of water can result in a condition called “water intoxication” or hyponatraemia.

Despite the exponential increase in knowledge in exercise physiology in the last two decades, the process of exercise physiologists and coaches changing old ideas and concepts and accepting new ones has been slow. Both should examine the new information available and use it to proceed with the next series of research studies and coaching concepts, respectively.


1. Noakes, T.D., Lore of Running, 4th ed., Oxford University Press, Cape Town, 2001.
2. Conley, D.L. and Krahenbuhl, GS., Running Economy and Distance Running Performance of Highly Trained Athletes, Medicine and Science in Sports and Exercise, 1980, 12, 357-360.
3. Hill, A.V. and Lupton, H., Muscular Exercise, Lactic Acid, and the Supply and Utilization of Oxygen, Quarterly Journal of Medicine, 1923, 16, 135-171.
4. Noakes, T.D., Maximal Oxygen Uptake: “Classical” Versus “Contemporary” Viewpoints: A Rebuttal, Medicine and Science in Sports and Exercise, 1998, 30, 1381-1398.
5. Noakes, T.D., Physiological Models to Understand Exercise Fatigue and the Adaptations that Predict or Enhance Athletic Performance, Scandanavian Journal of Medicine and Science in Sports, 2000, 10, 123-145.
6. Bassett, D.R. Jr. and Howley, E.T. Maximal Oxygen Uptake: “Classical” Versus “Contemporary” Viewpoints, Medicine and Science in Sports and Exercise, 1997, 29, 591-603.
7. Doherty, M., Nobbs, L. and Noakes, T.D., Low Frequency of the “Plateau Phenomenon” During Maximal Exercise in Elite British Athletes, European Journal of Applied Physiology and Occupational Physiology, 2003, 89, 619-623.
8. Abe, T., Kumagai, K. and Brechue, W.F., Fascicle Length of Leg Muscles is Greater in Sprinters than Distance Runners, Medicine and Science in Sports and Exercise, 2000, 32, 1125-1129.
9. Costill, D.L. and Winrow, E., Maximal Oxygen Intake Among Marathon Runners, Archives of Physical Medicine and Rehabilitation, 1970, 51: 317-320.
10. Pollock, M.L., Submaximal and Maximal Working Capacity of Elite Distance Runners, Part I: Cardiorespiratory Aspects, Annals of the New York Academy of Science, 1977, 301, 310-322.
11. Daniels, J., Daniels’ Running Formula, Human Kinetics, Champaign, IL, 1998.
12. Scrimgeour, A.G., Noakes, T.D., Adams, B. and Myburgh, K., The Influence of Weekly Training Distance on Fractional Utilization of Maximum Aerobic Capacity in Marathon and Ultramarathon Runners, European Journal of Applied Physiology and Occupational Physiology, 1986, 55, 202-209.
13. Noakes, T.D., Implications of Exercise Testing for Prediction of Athletic Performance: A Contemporary Perspective, Medicine and Science in Sports and Exercise, 1988, 20, 319-330.
14. Noakes, T.D, Myburgh, K.H. and Schall, R., Peak Treadmill Running Velocity During the V•O2 Max Test Predicts Running Performance, Journal of Sports Sciences, 1990, 8, 35-45.
15. Robergs, R.A, Ghiasvand, F. and Parker, D., Biochemistry of Exercise-Induced Metabolic Acidosis, American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 2004, 287, R502- R516.
16. Schwane, J.A., Johnson, S.R., Vandenakker, C.B. and Armstrong, R.B., Delayed-Onset Muscular Soreness and Plasma CPK and LDH Activities After Downhill Running, Medicine and Science in Sports and Exercise, 1983, 15, 51-56.
17. Brooks, G.A., Lactate Production Under Fully Aerobic Conditions: The Lactate Shuttle During Rest and Exercise, Federation Proceedings, 1986, 45, 2924-2929.
18. Brooks, G.A., The Lactate Shuttle During Exercise and Recovery, Medicine and Science in Sports and Exercise, 1986, 18, 360-368.
19. Rauch, H.G., Hawley, J.A., Noakes, T.D. and Dennis, S.C., Fuel Metabolism During Ultra-Endurance Exercise, Pflugers Archives, 1998, 436, 211-219.
20. Fletcher, W.M. and Hopkins, W.G., Lactic Acid in Amphibian Muscle, Journal of Physiology, 1907, 35, 247- 309.
21. Richardson, R.S., Noyszewski, E.A., Leigh, J.S. and Wagner, P.D., Lactate Efflux from Exercising Human Skeletal Muscle: Role of Intracellular PO2, Journal of Applied Physiology, 1998, 85, 627-634.
22. Dennis, S.C., Noakes, T.D. and Bosch, A.N., Ventilation and Blood Lactate Increase Exponentially During Incremental Exercise, Journal of Sports Sciences, 1992, 10, 437-449.
23. Campbell, M.E., Hughson, R.L. and Green, H.J., Continuous Increase in Blood Lactate Concentration During Different Ramp Exercise Protocols, Journal of Applied Physiology, 1989, 66, 1104-1107.
24. Hughson, R.L., Weisiger, K.H. and Swanson, G.D., Blood Lactate Concentration Increases as a Continuous Function in Progressive Exercise, Journal of Applied Physiology, 1987, 62, 1975-1981.
25. MacRae, H.S., Dennis, S.C., Bosch, A.N. and Noakes, T.D., Effects of Training on Lactate Production and Removal During Progressive Exercise in Humans, Journal of Applied Physiology, 1992, 72,1649-1656.
26. Bergman, B.C., Wolfel, E.E., Butterfield, G.E., Lopaschuk, G.D., Casazza G.A., Horning, M.A. and Brooks, G.A., Active Muscle and Whole Body Lactate Kinetics After Endurance Training in Men, Journal of Applied Physiology, 1999, 87, 1684-1696.
27. Pfitzinger, P., Training with Heart Rate, Running Times, 1994, 64-67.
28. Edwards, S., Smart Heart. High Performance Heart Zone Training, Heart Zones Company, Sacremento, California, 1997.
29. Gallagher, J., Using Your Body’s Tachometer, Marathon & Beyond, 1997, 1, 45-56.
30. Lambert, M.I., Mbambo, Z.H. and St Clair Gibson, A., Heart Rate During Training and Competition for Long-Distance Running, Journal of Sports Sciences, 1998, 16, S85-S90.
31. Clarkson, P.M. and Sayers, S.P., Etiology of Exercise-Induced Muscle Damage, Canadian Journal of Applied Physiology, 1999, 24, 234-248.
32. Morgan, D.L. and Allen, D.G., Early Events in Stretch-Induced Muscle Damage, Journal of Applied Physiology, 1999, 87, 2007-2015.
33. Jones, D.A., Newham, D.J. and Clarkson, P.M., Skeletal Muscle Stiffness and Pain Following Eccentric Exercise of the Elbow Flexors, Pain, 1987, 30, 233-242.
34. Clarkson, P.M., Nosaka, K. and Braun, B., Muscle Function After Exercise-Induced Muscle Damage and Rapid Adaptation, Medicine and Science in Sports and Exercise, 1992, 24, 512-520.
35. Noakes, T.D., Challenging Beliefs: Ex Africa Semper Aliquid Novi, Medicine and Science in Sports and Exercise, 1997, 29, 571-590.
36. Noakes, T.D, Kotzenberg, G., McArthur, P.S. and Dykman, J., Elevated Serum Creatine Kinase MB and Creatine Kinase BB-Isoenzyme Fractions After Ultra-Marathon Running, European Journal of Applied Physiology and Occupational Physiology, 1983, 52, 75-79.
37. Strachan, A.F., Noakes, T.D., Kotzenberg, G., Nel, A.E. and de Beer, F.C., C-Reactive Protein Concentrations During Long Distance Running, British Medical Journal: Clinical Research Edition, 1984, 289, 1249-1251.
38. Friden, J., Seger, J., Sjostrom, M. and Ekblom, B., Adaptive Response in Human Skeletal Muscle Subjected to Prolonged Eccentric Training, International Journal of Sports Medicine, 1983, 4, 177-183.
39. Friden, J., Muscle Soreness After Exercise: Implications of Morphological Changes, International Journal of Sports Medicine, 1984, 5, 57-66.
40. Friden, J., Sjostrom, M. and Ekblom, B., Myofibrillar Damage Following Intense Eccentric Exercise in Man, International Journal of Sports Medicine, 1983, 4, 170-176.
41. Byrnes, W.C., Clarkson, P.M., White, J.S., Hsieh,S.S., Frykman, P.N. and Maughan, R.J., Delayed Onset Muscle Soreness Following Repeated Bouts of Downhill Running, Journal of Applied Physiology, 1985, 59, 710-715.
42. Jackson, M.J., Muscle Damage During Exercise: Possible Role of Free Radicals and Protective Effect of Vitamin E. Proceedings of the Nutrition Society, 1987, 46, 77-80.
43. Tiidus, P.M., Massage and Ultrasound as Therapeutic Modalities in Exercise-Induced Muscle Damage, Canadian Journal of Applied Physiology, 1999, 24, 267-278.
44. Holtzhausen, L.M., Noakes, T.D., Kroning, B., de Klerk, M., Roberts, M. and Emsley, R., Clinical and Biochemical Characteristics of Collapsed Ultra-Marathon Runners, Medicine and Science in Sports and Exercise, 1994, 26, 1095-1101.
45. Roberts, W.O., A 12-yr Profile of Medical Injury and Illness for the Twin Cities Marathon, Medicine and Science in Sports and Exercise, 2000, 32, 1549-1555.
46. Noakes, T.D., Fluid Replacement During Exercise, Exercise and Sport Sciences Reviews, 1993, 21, 297-330.
47. Noakes, T.D., Dehydration During Exercise: What are the Real Dangers? Clinical Journal of Sport Medicine, 1995, 5, 123-128.
48. Holtzhausen, L.M. and Noakes, T.D., The Prevalence and Significance of Post-Exercise (Postural) Hypotension in Ultramarathon Runners, Medicine and Science in Sports and Exercise, 1995, 27, 1595-1601.
49. Holtzhausen, L.M. and Noakes, T.D., Collapsed Ultraendurance Athlete: Proposed Mechanisms and an Approach to Management, Clinical Journal of Sport Medicine, 1997, 7, 292-301.
50. Sandell, R.C., Pascoe, M.D. and Noakes, T.D., Factors Associated with Collapse During and After Ultramarathon Footraces: A Preliminary Study, The Physician and Sportsmedicine, 1988, 16, 86-94.
51. Gonzalez-Alonso, J., Teller, C., Andersen, S.L., Jensen, F.B., Hyldig, T. and Nielsen B., Influence of Body Temperature on the Development of Fatigue During Prolonged Exercise in the Heat, Journal of Applied Physiology, 1999, 86, 1032-1039.
52. Noakes, T.D., Myburgh, K.H., du Plessis, J., Lang, L., Lambert, M., van der Riet, C. and Schall, R., Metabolic Rate, Not Percent Dehydration, Predicts Rectal Temperature in Marathon Runners, Medicine and Science in Sports and Exercise, 1991, 23, 443-449.
53. Jardon, O.M., Physiologic Stress, Heat Stroke, Malignant Hyperthermia—A Perspective, Military Medicine, 1982, 147, 8-14.
54. Noakes, T.D., Adams, B.A., Myburgh, K.H., Greeff, C., Lotz, T., and Nathan, M., The Danger of an Inadequate Water Intake During Prolonged Exercise, A Novel Concept Re-visited, European Journal of Applied Physiology and Occupational Physiology, 1988, 57, 210-219.
55. Noakes, T.D., Hyperthermia, Hypothermia and Problems of Hydration in the Endurance performer, in: Shephard, R.J., ed., Endurance in Sport, Blackwell Publishers, London, 2000, 591-613.
56. Bosch, A.N., Dennis, S.C. and Noakes, T.D., Influence of Carbohydrate Ingestion on Fuel Substrate Turnover and Oxidation During Prolonged Exercise, Journal of Applied Physiology, 1994, 76, 2364-2372.
57. Shephard, R. J. and Kavanagh, T. J., Biochemical Changes with Marathon Running, Observations on Post- Coronary Patients, Proceedings of the 2nd International Symposium on Biochemistry of Exercise, Metabolic Adaptation to Prolonged Physical Exercise, Magglingen, Switzerland, 1973, 245-252.
58. Shephard, R.J. and Kavanagh, T., Fluid and Mineral Needs of Middle-Aged and Postcoronary Distance Runners, The Physician and Sportsmedicine, 1978, 6, 90-102.


Skeletal muscle: master or slave of the cardiovascular system?

By: Russell S. Richardson, Craig A. Harms, Bruno, Grassi, and Russell T. Hepple
Department of Medicine, University of California, San Diego, La Jolla, CA; Department of Kinesiology, Kansas State University, Manhatten, KS; and Istituto di Tecnologie Biomediche Avanzate, National Research Council, Milano, ITALY.

From: Skeletal muscle: master or slave of the cardiovascular system?

RUSSELL S. RICHARDSON, CRAIG A. HARMS, BRUNO, GRASSI, and RUSSELL T. HEPPLE. Skeletal muscle: master or slave of the cardiovascular system? Med. Sci. Sports Exerc., Vol. 32, No. 1, pp. 89–93, 1999.


Skeletal muscle and cardiovascular system responses to exercise are so closely entwined that it is often difficult to determine the effector from the affector. The purpose of this manuscript and its companion papers is to highlight (and perhaps assist in unraveling) the interdependency between skeletal muscle and the cardiovascular system in both chronic and acute exercise. Specifically, we elucidate four main areas: 1) how a finite cardiac output is allocated to a large and demanding mass of skeletal muscle, 2) whether maximal muscle oxygen uptake is determined peripherally or centrally, 3) whether blood flow or muscle metabolism set the kinetic response to the start of exercise, and 4) the matching of structural adaptations in muscle and the microcirculation in response to exercise. This manuscript, the product of an American College of Sports Medicine Symposium, unites the thoughts and findings of four researchers, each with different interests and perspectives, but with the common intent to better understand the interaction between oxygen supply and metabolic demand during exercise.


Although recognizing the numerous physiological systems and the many interactions during exercise, still perhaps the most significant interplay is between the cardiorespiratory system and skeletal muscle, which determines both O2 supply and demand (Fig. 1). At the beginning of exercise, the integrated response of the pulmonary, cardiovascular, and muscular systems characterize the V˙O2 on-kinetics. This kinetic response is highly sensitive to aerobic training (31) and can be measured both at the mouth and across a muscle (10). However, the role that each system plays in determining the V˙O2 on-kinetics continues to be the subject of considerable debate (4,18).

Beyond this transitional period, we encounter the issue of blood flow distribution, which is the appropriate distribution of a finite cardiac output among essential organs such as the brain, heart, intestines (48), and the metabolically very active skeletal muscle involved in the exercise (32). Which area of demand takes precedence as the metabolic requirements increase and the limits of cardiac output are approached (11)? The introduction of isolated skeletal muscle models (2,51) has highlighted this issue of skeletal muscle perfusion under conditions of maximal cardiac output versus a small muscle mass where central components are less taxed, allowing a greater level of skeletal muscle perfusion to be achieved (41,47). Additionally, these skeletal muscle models have proved fruitful in another long standing area of study: the determinants of maximal metabolic rate (V˙O2max), specifically whether V˙O2max is governed by O2 supply or O2 demand (35,43). Finally, the study of the structural interface between the cardiovascular system and skeletal muscle can be a powerful approach to elucidating the interplay between these two systems. It can be experimentally demonstrated that O2 conductance from blood to muscle cell plays an important role in determining V˙ O2max (37,52), suggestive of a passive role played by the muscle itself. However, when exposed to a repeated exercise stimulus, skeletal muscle now takes a very active role and demonstrates a remarkable plasticity (17) that positively affects exercise capacity (16).

Thus, here again the issue of who is the master and who the slave in the relationship between the cardiovascular system and skeletal muscle is open to debate.

Muscular Perfusion: Determined by Muscular Demand or Cardiovascular Supply?

The greatest demand for cardiac output during exercise is from skeletal muscle, as nearly 85% of total blood flow is directed to the working legs during maximal cycle ergometry (20,32). Several investigations have examined how different groups of skeletal muscle compete for the cardiac output during exercise and whether a “steal” phenomenon exists. Although Secher et al. (50) observed a decrease in leg blood flow when arm exercise was added to two legged cycle ergometry, more recent investigations have failed to corroborate these findings (36,44,49). However, the majority of data suggest that some degree of leg vasoconstriction or an attempt to vasoconstrict, as determined from norepinephrine spillover, occurs when arm exercise is added to leg exercise (44,49). Recently, a set of experiments have been conducted to determine whether a different group of skeletal muscles, those associated with breathing, influence cardiac output and its distribution during maximal exercise (11–13,56). These reports have demonstrated that respiratory muscles demand a significant portion of the cardiac output, primarily through stroke volume and total V˙O2, approximating 14–16% of the total (12). Additionally, it was shown that during heavy exercise, this metabolic demand from the respiratory muscles affects the distribution of cardiac output between the respiratory muscles and the legs such that leg vascular conductance and blood flow increases with respiratory muscle unloading and decreases with respiratory loading (11). Exercise performance may also be affected by the work of breathing during heavy exercise due to redistribution of blood flow between the chest wall and the locomotor muscles (56). Therefore, it appears that, in contrast to arm versus leg exercise, respiratory muscle work normally encountered during maximal exercise significantly influences cardiac output and its distribution.

V˙O2max: Governed by Oxygen Supply or Demand?

It has now been repeatedly demonstrated that an increase in O2 delivery can increase V˙O2max (1,3,5,21,30,34,38,43,55), which suggests that O2 supply limitation exists. As the isolated human quadriceps exercise does not approach the upper limits of cardiac output, this exercise paradigm has previously unveiled a skeletal muscle metabolic reserve and results in the highest mass specific V˙O2 and work rates recorded in man (37,41,46). This observation in of itself is evidence of O2 supply limitation of muscle V˙O2max. In a recent human knee-extensor study, the V˙O2max increased with an elevated O2 delivery (hyperoxia) demonstrating that in normoxic conditions even in the highly perfused isolated quadriceps, muscle V˙O2max is not limited by mitochondrial metabolic rate, but rather by O2 supply (35).

Although it is clear that in many scenarios an increase in O2 delivery can increase V˙O2max, it has also been demonstrated that this is not the sole determinant; in fact, the interaction between the convective and diffusive components of O2 transport may ultimately set the maximal metabolic rate (52). In the isolated canine gastrocnemius preparation, infusion of the allosteric modifier of hemoglobin RSR13 (Allos Therapeutics, Denver, CO) significantly increased P50, and at a constant arterial O2 delivery resulted in an increase in O2 extraction and a consequent increase in muscle V˙O2max (43). This indicates, for the first time, that the canine gastrocnemius muscle is normally O2 supply-limited, even when the animal is breathing 100% O2. In addition, the increase inV˙ O2max was proportional to the increase in venous PO2. Taken together, these findings support the concept that the diffusion of O2 between the red cell and the mitochondria plays a role in determining V˙O2max.

The insinuation that the production of lactate with progressively intense muscular work is evidence of inadequate intramuscular oxygenation has been long lived (15). Since then, the term “anaerobic threshold” has been used to describe the point at which lactate begins to accumulate in the blood, thought to indicate the inadequacy of O2 supply for the metabolic demand (54). Magnetic resonance spectroscopy, utilizing myoglobin as an endogenous probe of intracellular PO2 (29,53), in combination with the isolated human quadriceps model (38) has revealed that in hypoxic or normoxic exercise conditions net muscle lactate efflux is independent of intracellular PO2. The former increases whereas the latter remains constant during progressive incremental exercise (39). However, in hypoxia intracellular PO2 is systematically decreased in comparison to normoxia, whereas the changes in intracellular pH and muscle lactate efflux are accelerated. Whereas the latter observations indicate that a role for intracellular PO2 as a modulator of metabolism cannot be ruled out, arterial epinephrine levels are closely related to skeletal muscle lactate efflux in both normoxia and hypoxia and thus may be a major stimulus for the observed rise in muscle lactate efflux during progressively intense exercise and for the elevated lactate efflux in hypoxia. We would postulate that it is systemic and not intracellular PO2 that increases catecholamine responses in hypoxia and is therefore responsible for the correspondingly higher net lactate efflux (39).

Recently, evidence supporting the importance of intracellular PO2 in determining skeletal muscle V˙O2max has come to light (38). Studies of intracellular PO2 in trained human skeletal muscle with varied FIO2 suggest that in hyperoxia there is the expected rise in intracellular PO2 (due to increased mean capillary PO2), but this elevated O2 availability is now in excess of mitochondrial capacity (40). Indicating that intracellular PO2 is a determinant of V˙O2max in each FIO2 (12, 21, and 100% O2) but that in the latter case the increased intracellular PO2 results in diminishing returns with respect to an increase in V˙O2max. These observations are consistent with cellular metabolism that is moving toward a transition between O2 supply and O2 demand as a determinant of V˙O2max. It seems that further increases in intracellular PO2, beyond those recorded in hyperoxia, may have smaller effects upon V˙O2max until a plateau is reached and V˙O2max becomes invariant with intracellular PO2. From this point, intracellular PO2 may no longer be a determinant of skeletal muscle V˙O2max. This hyperbolic relationship, perhaps stemming from the origin, between intracellular O2 tension and cellular respiration is similar to data previously presented by Wilson et al. (57) in which the metabolic rate of isolated kidney cells was demonstrated to be O2 supply dependent below a certain O2 availability. Again, these myoglobin-associated PO2 data fit with the supply dependence of V˙O2max in healthy exercise trained human skeletal muscle (35,37).

V˙O2 On-Kinetics: Set by Blood Flow or Muscle Metabolism?

Upon a step transition from rest to exercise, or from a lower to higher workload, O2 uptake (V˙O2) lags behind the power output increase, following a time course usually termed V˙O2 on-kinetics. The mechanism(s) determining this kinetic response has been a matter of considerable debate between those who consider it mainly related to the rate of adjustment of O2 delivery to the exercising muscles and those supporting the concept that the V˙O2 on-kinetics is mainly set by an inertia of intramuscular oxidative metabolism.

In recent years, experiments in both exercising humans (9,10) and in the isolated in situ dog gastrocnemius preparation (7,8) have provided evidence in favor of the “metabolic inertia” hypothesis. Specifically, the transition from unloaded-to-loaded pedalling (below the “ventilatory threshold”) was studied in humans. 

Blood flow to one of the exercising limbs was determined continuously by a modified constant-infusion thermodilution technique, andV˙O2 across the limb was determined every ;5s by the Fick principle. Leg blood flow rose rapidly upon the change in work intensity, whereas arteriovenous O2 concentration difference across the limb did not increase during the first 10–15 s of the transition (10). During this type of metabolic transition, therefore, muscle O2 utilization kinetics lag behind the kinetics of bulk O2 delivery to muscle.

Heart transplant recipients show a slower V˙O2 on-kinetics compared with healthy controls. This slower V˙O2 onkinetics may be attributed to a slower adjustment of heart rate, cardiac output, and O2 delivery to muscles. In a group of heart transplant recipients, a “warm-up” exercise, performed before a rest-to-50-W transition, resulted in a slightly faster adjustment of cardiac output and more favourable conditions as far as O2 delivery to exercising muscles but did not speed up the V˙ O2 on-kinetics (9). Again, indicative of the lag in O2 uptake originating in the muscle itself.

By utilizing the isolated in situ dog gastrocnemius preparation, the metabolic transition from rest-to-electrically stimulated tetanic contractions corresponding to ;70% of V˙O2max was studied (7). The delay in the adjustment of convective O2 delivery to muscle was completely eliminated by pump-perfusing the muscle, at rest and during contractions, at a constant level of blood flow corresponding to the steady state value obtained during contractions in preliminary trials conducted with spontaneous adjustment of muscle blood flow (muscle perfused via the contralateral femoral artery). Adenosine was infused intra-arterially to prevent any vasoconstriction associated with the elevated muscle blood flow. Elimination of delay in convective O2 delivery did not affect muscle V˙O2 on-kinetics, which was not different to that observed in control conditions (7).

Finally, another study was conducted on the isolated in situ dog gastrocnemius preparation, during the same metabolic transition described above. Peripheral O2 diffusion was enhanced by having the dogs breathe a hyperoxic gas mixture and by the administration of RSR 13 (Allos Therapeutics), which right-shifts the oxy-hemoglobin dissociation curve. Mean capillary PO2 (PcapO2) was estimated by numerical integration. Hyperoxic breathing and RSR 13 significantly increased PcapO2 (i.e., the driving force for peripheral O2 diffusion) at rest and during contractions but did not affect muscle V˙O2 on-kinetics (8). Taken together, the results of this study and the previous one indicate that, in this experimental model, neither convective nor diffusive O2 delivery to muscle fibers affects muscleV˙ O2 on-kinetics, supporting the hypothesis that the latter is mainly set by an inertia of muscle oxidative metabolism. These conclusions appear in agreement with observations obtained by other authors in humans during step transitions to workloads lower than the “ventilatory threshold” (6,24). It should be noted, however, that these authors indicate that during step transitions to workloads higher than the “ventilatory threshold” the kinetics of O2 delivery to muscle appears to be a critical factor in determining the V˙O2 on-kinetics.

Plasticity of Skeletal Muscle: Microcirculatory Adaptation to Metabolic Demand?

The issue of whether skeletal muscle is master or slave of the cardiovascular system depends on frame of reference. Although acute manipulations of convective O2 delivery clearly show that O2 supply sets the upper limit of mitochondrial respiratory rate (42), interspecies comparisons (23) and study of adaptation to chronic conditions such as physical training show that capillarization (14,19) and mitochondrial development (28,45) are key components of the adaptive response in systemic V˙O2max. In addition, adaptations in the structural capacity for aerobic metabolism in skeletal muscle are closely regulated (e.g., close matching of capillary supply and fiber mitochondrial content) (26,33) and are maintained in proportion to the aerobic capacity of the whole organism (17). The study of adaptive variation in skeletal muscle structure within and between species has revealed design features that are uniform throughout muscles of widely varying metabolic demand. One of these features is that the size of the capillaryto- fiber interface rather than diffusion distance relates most closely to the structural capacity for O2 flux into muscle fibers (27). Recent studies have also shown that the size of the capillary-to-fiber interface is matched to mitochondrial volume/ fiber length with adaptation to training (33), electrical stimulation (26), and chronic hypoxia (25). These observations suggest another regulated design feature in skeletal muscle is matching the structural capacity for O2 flux to fiber metabolic demand (33).

Changes in capillarization and fiber mitochondrial content are important parts of the adaptive response to exercise training. In older humans, both high-intensity resistance training and aerobic training increase the size of the capillary-to-fiber interface (14). Furthermore, the change in V˙O2max is related to changes in the size of the capillary-to-fiber interface rather than capillary density, suggesting an increase in the structural capacity for O2 flux is an important feature of the adaptation in V˙O2max with both modes of training in this population (14).

Similarly, mitochondrial electron transport chain (ETC) capacity appears important to muscle V˙O2max. Poisoning of complex III (NADH-cytochrome c reductase) of the ETC results in a stepwise reduction in peak muscle O2 (27) and reduces peak muscle V˙O2 to pretraining levels in trained rat hindlimb muscle (45). It is noteworthy that this occurs even when muscle metabolism, blood flow, and convective O2 delivery are markedly lower than seen during maximal exercise in vivo (22).

In conclusion, there appears to be a paradox between the well-known increase in V˙O2max that occurs with increased O2 delivery and the proportional alterations in V˙O2max that accompany manipulations in mitochondrial oxidative capacity at submaximal O2 delivery and submaximal metabolic demand.

This, in conjunction with the observation that adaptation in skeletal muscle structural capacity for O2 flux (e.g., increased capillarization and fiber mitochondrial content) occurs in response to alterations in metabolic demand through exercise training and chronic hypoxia, supports an independent role of skeletal muscle in determining systemic V˙O2max.


It is clear that both on a functional and structural level the response of the cardiovascular system and skeletal muscle are closely linked. Here we have addressed the issue of which of these systems is dominant and which more submissive.

Although we offer insight to this question, perhaps the most striking observation is that a single answer would not be appropriate as the role of each system appears to be highly dependent upon a multitude of factors that together create the scenario under investigation. A change in one of these variables, for example, acute exercise becoming chronic exercise, will markedly alter the relationship between the cardiovascular system and skeletal muscle and change the answer to the question of control.

Funding was provided by NIH 17731, RR02305, and HL-15469, and Dr. Richardson and Dr. Harms were supported by Parker B. Francis Fellowships in Pulmonary Research.
Address for correspondence: Russell S. Richardson, Ph.D., Department of Medicine, University of California, San Diego, La Jolla, CA 90293-0623. E-mail: rrichardson@ucsd.edu.


1. ADAMS, R. P., and H. G.WELCH. Oxygen uptake, acid base status, and performance with varied inspired oxygen fractions. J. Appl. Physiol. 49:863–868, 1980.
2. ANDERSEN, P., and B. SALTIN. Maximal perfusion of skeletal muscle in man. J. Physiol. 366:233–249, 1985.
3. BARCLAY, J. K., and W. N. STAINSBY. The role of blood flow in limiting maximal metabolic rate in muscle. Med. Sci. Sports. 7:116–119, 1975.
4. CERRETELLI, P., D. W. RENNIE, and D. R. PENDERGAST. Kinetics of metabolic transients during exercise. In: Exercise Bioenergetics and Gas Exchange, P. Cerretelli, and B. J. Whipp (Eds.). Amsterdam: Elsevier, 1980, pp. 187–209.
5. DUHAYLONGSOD, F. G., J. A. GRIEBEL, D. S. BACON, W. G. WOLFE, and C. A. PIANTADOSI. Effects of muscle contraction on cytochrome a, a3 redox state. J. Appl. Physiol. 75:790 –797, 1993.
6. GERBINO, A., S. A.WARD, and B. J.WHIPP. Effects of prior exercise on pulmonary gas exchange kinetics during high-intensity exercise in humans. J. Appl. Physiol. 80:99 –107, 1996.
7. GRASSI, B., L. B. GLADDEN, M. SAMAJA, C. M. STARY, and M. C. HOGAN. Faster adjustment of O2 delivery does not affect VO2 onkinetics in isolated in situ canine muscle. J. Appl. Physiol. 85, 1998.
8. GRASSI, B., L. B. GLADDEN, C. M. STARY, P. D. WAGNER, and M. C. HOGAN. Peripheral O2 diffusion does not affect VO2 on-kinetics in isolated in situ canine muscle. J. Appl. Physiol. 85, 1998.
9. GRASSI, B., C. MARCONI, M. MEYER, M. RIEU, and P. CERRETELLI. Gas exchange and cardiovascular kinetics upon different exercise protocols in heart transplant recipients. J. Appl. Physiol. 82:1952–1962, 1997.
10. GRASSI, B., D. C. POOLE, R. S. RICHARDSON, D. R. KNIGHT, B. K. ERICKSON, and P. D. WAGNER. Muscle O2 uptake kinetics in humans: implications for metabolic control. J. Appl. Physiol. 80:988–998, 1996.
11. HARMS, C. A., M. A. BABCOCK, S. R. MCCLARAN, et al. Respiratory muscle work compromises leg blood flow during maximal exercise. J. Appl. Physiol. 82:1573–1583, 1997.
12. HARMS, C. A., T. WETTER, S. R. MCCLAREN, et al. Effect of respiratory muscle work on cardiac output and its distribution
during maximal exercise. J. Appl. Physiol. 85:609–618, 1998.
13. HARMS, C. A., T. WETTER, C. ST. CROIX, D. F. PEGELOW, and J. A. DEMPSEY. Increased power output at VO2max with respiratory muscle unloading. Med. Sci. Sports. Exerc. 30:S41, 1998.
92 Official Journal of the American College of Sports Medicine http://www.msse.org
14. HEPPLE, R. T., S. L. M.MACKINNON, J. M. GOODMAN, S. G. THOMAS, and M. J. PLYLEY. Resistance and aerobic training in older men: effects on VO2 peak and the capillary supply to skeletal muscle. J. Appl. Physiol. 82:1305–1310, 1997.
15. HILL, A. V., C. N. H. LONG, and H. LUPTON. Muscular exercise, lactic acid, and the supply and utilization of oxygen. Part IV: the
oxygen debt at the end of exercise. Proc. R. Soc. (Lond.) Series B 97:127–137, 1924.
16. HOPPELER, H., H. HOWALD, K. CONLEY, et al. Endurance training in humans: aerobic capacity and structure of skeletal muscle. J. Appl. Physiol. 59:320 –327, 1985.
17. HOPPELER, H., and S. L. LINDSTEDT. Malleability of skeletal muscle in overcoming limitations: structural elements. J. Exp. Biol. 115: 355–364, 1985.
18. HUGHSON, R. L., J. K. SHOEMAKER, M. E. TSCHAKOVSKY, and J. M. KOWALCHUCK. Dependence of muscle VO2 on blood flow dynamics at the onset of forearm exercise. J. Appl. Physiol. 81:1619– 1626, 1996.
19. INGJER, F. Maximal aerobic power related to capillary supply in the quadriceps femoris muscle in man. Acta Physiol. Scand. 104:238–240, 1978.
20. KNIGHT, D. R., D. C. POOLE, W. SCHAFFARTZIK, et al. Relationship between body and leg VO2 during maximal cycle ergometry. J. Appl. Physiol. 73:1114 –1121, 1992.
21. KNIGHT, D. R., W. SCHAFFARTZIK, D. C. POOLE, M. C. HOGAN, D. E. BEBOUT, and P. D. WAGNER. Hyperoxia increases leg maximal oxygen uptake. J. Appl. Physiol. 75:2586 –2594, 1993.
22. LAUGHLIN, M. H., and R. B. ARMSTRONG. Muscular blood flow distribution patterns as a function of running speed in rats. Am. J. Physiol. 243:H296–H306, 1982.
23. LINDSTEDT, S. L., D. J. WELLS, J. H. JONES, H. HOPPELER, and H. A. THRONSON, JR. Limitations to aerobic performance in mammals: interaction of structure and and demand. Int. J. Sports Med. 9:210 –217, 1988.
24. MACDONALD, M., P. K. PEDERSEN, and R. L. HUGHSON. Acceleration of VO2 kinetics in heavy submaximal exercise in hyperoxia and prior high-intensity exercise. J. Appl. Physiol. 83:1318–1325, 1997.
25. MATHIEU-COSTELLO, O., P. J. AGEY, L. WU, J. M. SZEWCZAK, and R. E. MCMILLEN. Increased fiber capillarization in flight muscle of finch at altitude. Respir. Physiol. 111:189 –199, 1998.
26. MATHIEU-COSTELLO, O., P. J. AGEY, L. WU, J. HANG, and T. H. 0ADAIR. Capillary-to-fiber surface ratio in rat fast-twitch hindlimb muscles after chronic electrical stimulation. J. Appl. Physiol. 80: 904–909, 1996.
27. MATHIEU-COSTELLO, O., R. K. SAUREZ, and P. W. HOWCHACHKA. Capillary-to-fiber geometry and mitochondrial density in hummingbird flight muscle. Respir. Physiol. 89:113–132, 1992.
28. MCALLISTER, R. M., and R. L. TERJUNG. Acute inhibition of respiratory capacity of muscle reduces peak oxygen consumption. Am. J. Physiol. 259:C889–C896, 1990.
29. NOYSZEWSKI, E. A., E. L. CHEN, R. REDDY, Z. WANG, and J. S. LEIGH. A simplified sequence for observing deoxymyoglobin signals in vivo: myoglobin excitation with dynamic unexcitation and saturation of water and fat. Magn. Reson. Med. 38:788 –792, 1997.
30. PELTONEN, J. E., J. RANTAMAKI, S. P. NIITTYMAKI, K. SWEINS, J. T. VIITASALO, and H. K. RUSKO. Effects of oxygen fraction in inspired air on rowing performance. Med. Sci. Sports. Exerc. 27:573–579, 1995.
31. PHILLIPS, S. M., H. J. GREEN, M. J. MACDONALD, and R. L. HUGHSON. Progressive effect of endurance training on VO2 kinetics at the onset of submaximal exercise. J. Appl. Physiol. 79:1914–1920, 1995.
32. POOLE, D. C., G. A. GAESSER, M. C. HOGAN, D. R. KNIGHT, and P. D. WAGNER. Pulmonary and leg VO2 during submaximal exercise: implications for muscular efficiency. J. Appl. Physiol. 72: 805–810, 1992.
33. POOLE, D. C., and O. MATHIEU-COSTELLO. Relationship between fiber capillarization and mitochondrial volume density in control and trained rat soleus and plantaris muscles. Microcirculation 3:175–186, 1996.
34. POWERS, S. K., J. LAWLER, J. A. DEMPSEY, S. DODD, and G. LANDRY. Effects of incomplete pulmonary gas exchange on VO2max. J. Appl. Physiol. 66:2491–2495, 1989.
35. RICHARDSON, R. S., B. GRASSI, T. P. GAVIN, L. J. HASELER, K. TAGORE, J. ROCA, and P. D. WAGNER. Evidence of supply-dependent VO2max in the exercise-trained human quadriceps. J. Appl. Physiol. 86:1048 –1053, 1999.
36. RICHARDSON, R. S., B. KENNEDY, D. R. KNIGHT, and P. D. WAGNER. High muscle blood flows are not attenuated by recruitment of additional muscle mass. Am. J. Physiol. 269:H1545–H1552, 1995.
37. RICHARDSON, R. S., D. R. KNIGHT, D. C. POOLE, et al. Determinants of maximal exercise VO2 during single leg knee extensor exercise in humans. Am. J. Physiol. 268:H1453–H1461, 1995.
38. RICHARDSON, R. S., E. A. NOYSZESKI, K. F. KENDRICK, J. S. LEIGH, and P. D. WAGNER. Myoglobin O2 desaturation during exercise: evidence of limited O2 transport. J. Clin. Invest. 96:1916–1926, 1995.
39. RICHARDSON, R. S., E. A. NOYSZEWSKI, J. S. LEIGH, and P. D. WAGNER. Lactate efflux from exercising human skeletal muscle: role of intracellular PO2. J. Appl. Physiol. 85:627– 634, 1998.
40. RICHARDSON, R. S., E. A. NOYSZEWSKI, J. S. LEIGH, and P. D. WAGNER. Cellular PO2 as a determinant of maximal mitochondrial O2 consumption in trained human skeletal muscle. J. Appl. Physiol. 87:325–331; 1999.
41. RICHARDSON, R. S., D. C. POOLE, D. R. KNIGHT, et al. High muscle blood flow in man: is maximal O2 extraction compromised? J. Appl. Physiol. 75:1911–1916, 1993.
42. RICHARDSON, R. S., and B. SALTIN. Human muscle blood flow and metabolism studied in the isolated quadriceps muscles. Med. Sci. Sports. Exerc. 30:28 –33, 1998.
43. RICHARDSON, R. S., K. TAGORE, L. HASELER, M. JORDAN, and P. D. WAGNER. Increased VO2max with right shifted HbO2 dissociation curve at a constant O2 delivery in dog muscle in situ. J. Appl. Physiol. 84:995–1002, 1998.
44. RICHTER, E. A., B. KIENS, M. HARGREAVES, and M. KAEJER. Effect of arm cranking on leg blood flow and noradrenaline spillover during leg exercise in man. Acta Physiol. Scand. 144:9 –14, 1992.
45. ROBINSON, D. M., R. W. OGILIVIE, P. C. TULLSON, and R. L. TERJUNG. Increased peak oxygen consumption of trained muscle requires increased electron flux capacity. J. Appl. Physiol. 77: 1941–1952, 1994.
46. ROWELL, L. B. Muscle blood flow how high can it go? Med. Sci. Sports. Exerc. 20:S97–S103, 1988.
47. ROWELL, L. B., B. SALTIN, B. KIENS, and N. J. CHRISTENSEN. Is peak quadriceps blood flow in humans even higher during exercise with hypoxemia? Am. J. Physiol. 251:H1038–H1044, 1986.
48. SALTIN, B. Hemodynamic adaptions to exercise. Am. J. Cardiol. 55:42D–47D, 1985.
49. SAVARD, G. K., E. A. RICHTER, S. STRANGE, B. KIENS, N. J. CHRISTENSEN, and B. SALTIN. Norepinephrine spillover from skeletal muscle during exercise: role of muscle mass. Am. J. Physiol. 257:H1812–H1818, 1989.
50. SECHER, N. H., J. P. CLAUSEN, K. KLAUSEN, I. NOER, and J. TRAPJENSEN. Central and regional circulatory effects of adding arm exercise to leg exercise. Acta Physiol. Scand. 100:288 –297, 1977.
51. STAINSBY, W. N., and A. B. OTIS. Blood flow, blood oxygen tension, oxygen uptake, and oxygen transport in skeletal muscle. Am. J. Physiol. 206:858–866, 1964.
52. WAGNER, P. D. Gas exchange and peripheral diffusion limitation. Med. Sci. Sports. Exerc. 24:54 –58, 1992.
53. WANG, Z., E. A. NOYSZEWSKI, and J. S. LEIGH. In vivo MRS measurement of deoxymyoglobin in human forearms. Magn. Reson. Med. 14:562–567, 1990.
54. WASSERMAN, K., and M. B. MCILROY. Detecting the threshold of anaerobic metabolism in cardiac patients during exercise. Am. J. Cardiol. 14:844–859, 1964.
55. WELCH, H. G. Hyperoxia and human performance: a brief review. Med. Sci. Sports. Exerc. 14:253–262, 1982.
56. WETTER, T. J., C. A. HARMS, C. ST. CROIX, D. F. PEGLOW, and J. A. DEMPSEY. Effects of respiratory muscle loading and unloading on time to exhaustion during cycle ergometry. Med. Sci. Sports. Exerc. 30:S190, 1998.
57. WILSON, D. F., M. ERECINSKA, C. DROWN, and I. A. SILVER. Effect of oxygen tension on cellular energetics. Am. J. Physiol. 233: C135–C140, 1977.