Photo by Lisa Bettany.

By Nicola Maffulli, Umile Giuseppe Longo, Vincenzo Denaro, Consultant Trauma and Orthopaedic Surgeon, University Hospital of North Staffordshire, Keele University School of Medicine

We read with interest the Review Article “Rotator cuff tendinopathy: A review”, by Lewis.

This manuscript may have been submitted before the publication of our investigations. Nevertheless, we would like to call your attention to the fact that we have performed several studies on the aetiology, histopathology and management of rotator cuff tendinopathy.

We investigated supraspinatus tendon samples obtained from patients undergoing arthroscopic repair of a rotator cuff tear to examine the distribution of tendinopathic changes associated with this condition. At arthroscopy, a full thickness supraspinatus tendon biopsy was harvested close to the tear edge. We found more frequent tendon changes on the articular side of the rotator cuff 4.

We found more cartilage-like changes in patients affected by rotator cuff tears, but not in our control group.Recent biomechanical data suggest that the stress-shielded and transversely-compressed side of the enthesis has a distinct tendency to develop cartilage-like or atrophic changes in response to the lack of tensile load 2,7,9,10. Over a long period, this process may develop into a primary degenerative lesion in that area of the tendon. This may explain why the tendinopathy is not always clearly activity related, and can be strongly correlated with age. In this manner, it could almost be considered an ”underuse” injury rather than an overuse injury as a result of stress-shielding 7,9,10. The formation of cartilage-like changes in the enthesis in many ways can be considered a physiological adaptation to the compressive loads 12-14. It may not allow the tendon to maintain its ability to withstand high tensile loads in that region of the tendon.

As the stress-shielding may have led to tensile weakening over time, an injury may occur more easily in this region. In this manner, insertional tendinopathy could be considered an overuse injury, but predisposed by pre -existing weakening of the tendon 12-14.

In another study 3 to evaluate the histopathological features of macroscopic intact tendon portion of patients with rotator cuff tears, we demonstrated that the supraspinatus tendons of patients undergoing arthroscopic repair for a rupture show profound histopathologic changes, while the tendons of aged persons with no known tendon abnormalities have, as a group, little histological evidence of pathological changes.

Moreover, tendon changes are not only localized at the site of rupture, but also in the macroscopic intact tendon portion.

Several centres are undertaking studies on tendinopathy 11,16,17, and the individual studies are unlikely to be large enough to result in adequate power for reliable evaluation. Therefore, combining the data from those studies with a similar study design will be essential. Consistent high- quality pathology data are thus remarkably important for the success of the studies. Two scoring systems can be used for classification of the histopathological findings of tendinopathy: the Movin score 15 and its validated modifications 4,6,12, and the Bonar score 1. We performed a study to answer the question whether these two scores of abnormal tendon tissue were comparable 8. In our hands, Movin and Bonar scores assess the same characteristics of tendon pathology.

In an frequency-matched case-control study we determined the plasma glucose levels in non diabetic patients with rotator cuff tear 5. We found that normal, but in the high range of normal, increasing plasma glucose levels may be a risk factor for rotator cuff tear.

Lastly, although it is likely that the histopathology of tendinopathy is similar, of not the same, regardless of its location, this has only been shown in a formal fashion in the Achilles and patellar tendons 12: we were slightly surprised of the fact that a number of papers dealing with pathology of other tendons (i.e., patellar tendon, Achilles Tendon, and extensor carpi radialis brevis tendon (tennis elbow) are quoted referring to rotator cuff tendinopathy (references n°23,24,25,26,81,94,96,97,98, 147,148).

References
1. Cook, J.; Feller, J.; Bonar, S.; and Khan, K. Abnormal tenocyte morphology is more prevalent than collagen disruption in asymptomatic athletes’ patellar tendons. J Orthop Res 2004;22:334-338.
2. Gardner, K.; Arnoczky, S. P.; Caballero, O.; and Lavagnino, M. The effect of stress-deprivation and cyclic loading on the TIMP/MMP ratio in tendon cells: An in vitro experimental study. Disabil Rehabil 2008:1-7.
3. Longo, U. G.; Franceschi, F.; Ruzzini, L.; Rabitti, C.; Morini, S.; Maffulli, N.; and Denaro, V. Histopathology of the supraspinatus tendon in rotator cuff tears. Am J Sports Med 2008;36:533-8.
4. Longo, U. G.; Franceschi, F.; Ruzzini, L.; Rabitti, C.; Morini, S.; Maffulli, N.; Forriol, F.; and Denaro, V. Light microscopic histology of supraspinatus tendon ruptures. Knee Surg Sports Traumatol Arthrosc 2007;15:1390-4.
5. Longo, U. G.; Franceschi, F.; Ruzzini, L.; Spiezia, F.; Maffulli, N.; and Denaro, V. Higher fasting plasma glucose levels within the normoglycemic range and rotator cuff tears. Br J Sports Med 2008;
6. Maffulli, N.; Barrass, V.; and Ewen, S. W. Light microscopic histology of achilles tendon ruptures. A comparison with unruptured tendons. Am J Sports Med 2000;28:857-63.
7. Maffulli, N.; Khan, K. M.; and Puddu, G. Overuse tendon conditions: time to change a confusing terminology. Arthroscopy 1998;14:840-3.
8. Maffulli, N.; Longo, U. G.; Franceschi, F.; Rabitti, C.; and Denaro, V. Movin and Bonar scores assess the same characteristics of tendon histology. Clin Orthop Relat Res 2008;466:1605-11.
9. Maffulli, N.; Reaper, J.; Ewen, S. W.; Waterston, S. W.; and Barrass, V. Chondral metaplasia in calcific insertional tendinopathy of the Achilles tendon. Clin J Sport Med 2006;16:329-34.
10. Maffulli, N.; Sharma, P.; and Luscombe, K. L. Achilles tendinopathy: aetiology and management. J R Soc Med 2004;97:472-6.
11. Maffulli, N.; Testa, V.; Capasso, G.; Bifulco, G.; and Binfield, P. M. Results of percutaneous longitudinal tenotomy for Achilles tendinopathy in middle- and long-distance runners. Am J Sports Med 1997;25:835-40.
12. Maffulli, N.; Testa, V.; Capasso, G.; Ewen, S. W.; Sullo, A.; Benazzo, F.; and King, J. B. Similar histopathological picture in males with Achilles and patellar tendinopathy. Med Sci Sports Exerc 2004;36:1470-5.
13. Maffulli, N.; Waterston, S. W.; and Ewen, S. W. Ruptured Achilles tendons show increased lectin stainability. Med Sci Sports Exerc 2002;34:1057-64.
14. Maffulli, N.; Wong, J.; and Almekinders, L. C. Types and epidemiology of tendinopathy. Clin Sports Med 2003;22:675-92.
15. Movin, T.; Gad, A.; Reinholt, F.; and Rolf, C. Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients. Acta Orthop Scand 1997;68:170-5.
16. Murrell, G. A. Oxygen free radicals and tendon healing. J Shoulder Elbow Surg 2007;16:S208-14.
17. Murrell, G. A. Using nitric oxide to treat tendinopathy. Br J Sports Med 2007;41:227-31.

By Fergus Joseph Dignan, Civilian Medical Practitioner, MOD

I very much enjoyed reading the ‘warm up’ article by Steven N Blair in the January edition of BJSM. The first study that he quoted on attributable fractions for all cause deaths was a real eye popper!

I was very surprised to see that low cardiorespiratory fitness was a greater attributable risk factor (in both sexes) than obesity, smoking, high cholesterol, and diabetes, as well as hypertension in women.

The second study was almost equally as fascinating. This illustrated that the risk of cardiovascular mortality in Type 2 diabetes in the obese category who took moderate to high levels of exercise, was half that of diabetics in the normal weight category who took no exercise. There was one thing that puzzled me and that was the histograms illustrated that for the type 2 diabetics who took low levels of exercise the cardiovascular risk was the same for those in the obese category as in the normal weight group.

This article will certainly alter the way that I communicate health promotion to my patients, and I would like to congratulate Steven Blair for such a stimulating article.

A recent editorial by Babette Pluim entitled, “A doping sinner is not always a cheat” [excerpt below], has created some fiery discussion amongst BJSM editors and readers this month.

The doping rules these days are really tough. The basic principle is: first offense gets a 2 year ban, second offence a lifetime ban. Everyone seems to agree that doping is cheating, and those who cheat should be sanctioned, so if an athlete provides a positive sample in any sporting situation, the inference must be that they are cheating. Unfortunately, both for the athlete and the anti-doping system, that is not always the case.

Here is a selection of BJSM editors’ & readers’ reactions:

“Drug cheats – or are they?”
By Dr Tim Wood, Chief medical officer for the Australian Open Tennis Championship and a member of Tennis Australia’s Anti-Doping Review Board

With the formation of the World Anti-Doping Agency (WADA) and the universal harmonization in the fight against the drug cheats in the late 90s everyone applauded. What we didn’t realize at the time was how many ’innocent’ victims would be caught up in the new rules and regulations. I therefore applaud Dr Babette Pluim’s BJSM editorial which reviews the positive doping cases recorded by the International Tennis Federation from 2001-07. She found that the majority of so-called ‘positive’ tests are no more than innocent mistakes by players and officials alike. Nevertheless, the trauma suffered and the tainting of these players is irreversible.

Having been involved in professional tennis for the last 7 years, I also experience frustration at the paperwork required to allow player with genuine medical conditions to take legitimate, scientifically proven drugs that certainly do not enhance performance. The most recent ‘crazy redtape’ is the requirement for a full Therapeutic Use Exemption (TUE) to allow an athlete to have intravenous fluid during elective surgery (Babette has some stories about that!).

Fortunately, it would appear that sanity may be about to prevail on at least three fronts. First, abbreviated TUEs (ATUES for those in the know, even though it sounds like a sneeze) that are currently required for intra-articular cortisone injections will be changed to notification via ADAMS (WADA’s web-based anti-doping management system). Second, ATUEs for beta-2 agonists will be valid for four years instead of needing to be renewed annually but this will come with more stringent proof of the player’s asthmatic status. And finally, many of us hope that the intravenous rule will revert to the 2007 ruling ‘… except for genuine medical situations’.

Everyone involved in professional sport strongly supports WADA and their efforts to catch the cheats but the rules shouldn’t catch innocent athletes, particularly those with genuine medical conditions.

“WADA is on the verge of losing the plot”
By John Orchard, Sports Physician

The idea to create the World Anti-Doping Agency (WADA) was a good one, particularly for international sports. It meant that rogue states like the USA, which had a track record of going soft on their own athletes who tested positive, could be forced to implement universal sanctions.

The big problem with WADA is that it is a monopoly. And it is being run increasingly like one, currently under the Presidency of our own ex-politician John Fahey. WADA’s aim should be to stamp out cheating in sport. This is quite difficult to do, as the cheats are usually very clever. WADA instead is trying to maximise scalps of athletes who “test positive for drugs”, without apparent concern for whether they are actually cheating. Instead of concentrating only on the genuinely performance-enhancing (and usually difficult-to-detect) drugs, the WADA banned list is ever-expanding. It now includes commonly used medications which are much easier to detect and “might conceivably” be used for performance-enhancing in rare circumstances. Whether these rare circumstances exist when an athlete tests positive don’t seem faze WADA, as there is a presumption of guilt rather than innocence.

Banned medications now include asthma puffers and cortisone injections, which are generally considered by doctors and scientists to not be performing-enhancing. Intravenous fluids, including those given for an anaesthetic as part of surgery, are now also banned as of 2008. The status quo is now the farcical situation that the vast majority of athletes are breaking the WADA code whenever they go in for elective surgery. In theory, the only thing stopping these athletes from being suspended is that drug testers aren’t (yet) following them into hospitals.

An editorial just published in the British Journal of Sports Medicine found that in the last 5 years of drug testing in tennis, it was accepted that 68% of the players who were banned for positive drug tests were not actually cheating. They were banned presumably because WADA wanted to increase their tally of convictions. They include cases such as known asthmatics taking puffers such as Ventolin for asthma attacks, but whose ‘permits’ to treat their asthma with appropriate medication had either recently expired or been faxed to the wrong number. In 2009, WADA has plans that asthmatics should apply to a panel to ‘prove’ they have asthma, or else they will be banned from sport for using their puffers. The Howard government basically held the funding gun to the head of all Australian sports in 2005 and forced them to sign up to WADA, despite many sports fearing the situation we are now in. This being that the universal drug code has become draconian and the sports have signed away all rights to do anything about it.

“Accidental cheating?”
By Giuseppe Lippi, Associate Professor of Clinical Biochemistry, Università di Verona

In an overview of the 40 most recent cases of doping in tennis, Babette Pluim highlighted that in only 13 of the cases (32%) was a prohibited substance taken to enhance performance, whereas most frequently banned substances were taken with no intent to enhance performance or without (significant) fault or negligence.1

I definitely agree that products that are on the list of prohibited substances should be critically reviewed, but I also emphasize that the current anti-doping policy is essentially a costly, repressive, zero tolerance approach, which seems only partly successful.2 It is also to mention, however, that there may be additional explanations to justify adverse findings on antidoping testing, which have little to do with cheating.

The use of dietary supplements is commonplace in sports, most elite athletes using some form of licit supplementation to burst athletic performance and improve recovery after training or competition. Nevertheless, there is widespread evidence that some of these legitimate products, especially those sold on the “black market”, contain banned substances that are not claimed as a result of poor manufacturing practice or adulteration.

Contaminants mostly include anabolic androgenic steroids, hormones, ephedrine and caffeine.3,4 Indeed, in some cases the adverse findings might be the consequence of deliberate cheating. However, we should still consider the possibility that some positive tests might arise from unintentional consumption of prohibited substances, contaminating dietary supplements. In this respect, not only antidoping agencies should focus on products that are truly harmful and performance-enhancing, but they should also issue a clear regulation on the use of nutritional supplements and establish appropriate bans for inadvertent use of banned molecules. Doping is always to blame, especially when the athletes use illicit methodsor substances that might produce a serious risk for their health. However, as different sanctions are imposed when crimes are intentional or preterintentional, bans should also be clearly differentiated from deliberate and unintentional positivity to banned substances.

References

1. Pluim B. A doping sinner is not always a cheat. Br J Sports Med 2008;42:549-50.

2. Kayser B, Smith AC. Globalisation of anti-doping: the reverse side of the medal. BMJ 2008 Jul 4;337:a584. doi: 10.1136/bmj.a584.

3. Maughan RJ. Contamination of dietary supplements and positive drug tests in sport. J Sports Sci 2005;23:883-9.

4. Linksvan der Merwe PJ, Grobbelaar E. Unintentional doping through the use of contaminated nutritional supplements. S Afr Med J 2005;95:510- 1.

Another excellent patient information to download!

Patient Information Sheet 17 - Lateral hip pain

More patient information sheets can be found here.

Another response by Fergus J. Dignan to Noakes’ paper <em>How did A V Hill understand the VO2max and the “plateau phenomenon”? Still no clarity?

Click to view more reader responses to this article.

Dear Editor,

I very much enjoyed reading the Review article (1) by Professor Noakes and the letter (2) in the same edition of the BJSM July 2008.

As he rightly states measurement of VO2max has several limitations in determining an athlete’s potential. He also pointed out in the letter that research has shown that ‘the rating of perceived exertion (RPE) rises as a linear function of the duration of exercise that remains’, and extrapolation from this ‘that humans have an exquisite capacity to predict accurately the duration of exercise they will be able to sustain at any exercise intensity’.

Would it therefore not be possible to determine an athlete’s optimal running distance by getting them to run on a treadmill for 10 minutes and asking them to run as fast as possible for imagined
distances of 5k, 10k, 40k, etc?

1. NOAKES TD. Testing for maximum oxygen consumption has produced a brainless model of human exercise performance. Br J Sports Med 2008; 42:551-555

2. NOAKES TD. Rating of perceived exertion as a predictor of the duration of exercise that remains until exhaustion. Br J Sports Med 2008; 42:623-624

Tennis elbow - impingement at the common extensor origin? Case report

By E Zeisig, M Fahlstrom, L Ohberg, and H Alfredson

Abstract
Full Text

We thank Dr Knobloch and colleagues for raising questions of the influence of elbow position on the area with high blood flow seen in the common extensor origin and outcome measurement in patients with painful tennis elbow. The first question raised is if the grip strength with 900 elbow flexion might change as well as the grip strength with extended elbow changes in response to the intratendinous injection treatment.[1] This question will be answered in an original article in the future.

The other question raised is if the area with high blood flow inside the area of structural changes seen on ultrasound examination is influenced by elbow position. One of the findings on ultrasound examinations of the common extensor origin is “tendon thickening”.[2] We believe that this thickening in some cases is exposed to internal compressive forces. This belief is based on the findings we have made when we have performed ultrasound and colour Doppler examinations during elbow movement. When the elbow is flexed 70-800 there is plenty of space between the head of the radial bone and the lateral epicondyle but during extension of the elbow, the radius makes a movement towards the lateral epicondyle and there will be impingement of the area with structural changes and high blood flow (Figure 1a and 1c). The raised pressure in the thickened tendon due to impingement at the extensor origin will diminish the high blood flow (not detectable), and like on palpation (applying external compressive force), the patient will experience pain. To perform an intratendinous injection targeting the area with high blood flow, the blood flow must be visible on colour Doppler examination which is the case when the elbow is flexed 70- 800, not when the elbow is extended (Figure 1b and 1d). This theory of impingement at the common extensor origin in tennis elbow might be the explanation behind good results in arthroscopic debridement of the area.[3] Other authors have also noted impingement during elbow arthroscopy, Mullet and colleagues classified their findings as degenerative capsular fold.[4] We hope this case rapport is an acceptable answer to the question at the time being. Further studies of the biomechanical prosperities of the elbow and the effect on the soft tissue are highly indicated. Are some individuals more prone to develop recalcitrance painful tennis elbow?

REFERENCES

[1] Zeisig E, Fahlstrom M, Ohberg L, et al. Pain relief after intratendinous injections in patients with tennis elbow: results of a randomised study. British journal of sports medicine. 2008 Apr;42(4):267- 71.

[2] Levin D, Nazarian LN, Miller TT, et al. Lateral epicondylitis of the
elbow: US findings. Radiology. 2005 Oct;237(1):230-4.

[3] Cummins CA. Lateral epicondylitis: in vivo assessment of arthroscopic debridement and correlation with patient outcomes. The American journal of sports medicine. 2006 Sep;34(9):1486-91.

[4] Mullett H, Sprague M, Brown G, et al. Arthroscopic treatment of lateral epicondylitis: clinical and cadaveric studies. Clinical orthopaedics and related research. 2005 Oct;439:123-8.

BJSM peer review of Noakes’ paper, “How did A.V. Hill understand the VO2max and the “plateau phenomenon”? Still no clarity?” by Mark Burnley, Department of Sport and Exercise Science, Aberystwyth University, Wales, UK.

“There is a “biologically plausible explanation” for lower supramaximal oxygen uptake”

I read with concern the recent review of Noakes[1] accepted for publication in the journal. Noakes suggests that there is no “biologically plausible explanation” for the observation of lower oxygen uptake (VO2) values in supramaximal exercise compared to incremental exercise.[2] Noakes further argues that those supramaximal data are therefore questionable and should be excluded, thus resulting in the conclusions of the original authors being disproved. Noakes’ first assertion (biological implausibility) is incorrect. His second assertion is at best biased, and at worst could be viewed as endorsing unethical practices.

The observation of lower VO2 values at exhaustion during supramaximal exercise could be attributed to normal biological variation (random error). However, the kinetics of VO2 dictates the rate at which VO2 rises to meet the energetic demand. In situations where exhaustion occurs before the kinetics drive VO2 to the maximum (so-called “extreme intensity exercise”[3]), VO2 will be lower than that measured in an incremental test performed to exhaustion. The boundary between “severe intensity exercise” (wherein VO2 reaches VO2max before exercise termination) and “extreme exercise” has been estimated to be ~110-135% VO2max,[3,4] providing the “biologically plausible explanation” Noakes wishes to deny.

To argue exclusion of the supramaximal data is ethically troubling.

Such exclusion, in this case solely for the purpose of interpretation, results in grossly biased conclusions. For any scientist, particularly one as influential as Noakes, to adopt such an approach does a disservice to students of exercise science. It would be tragic indeed
if these impressionable proto-scientists use Noakes’ precedence to endorse unethical data manipulation techniques to promote their own subjective opinions. Accordingly, I call upon Noakes to retract these statements to prevent further misleading interpretations from entering the literature.

References

1. Noakes TD. Peer review/fair review: How did A.V. Hill understand the VO2max and the “plateau phenomenon”? Still no clarity? Brit J Sports Med, in press. DOI: 10.1136/bjsm.2008.046771.

2. Hawkins MN, Raven PD, Snell PG, Stray-Gundersen J, Levine BD. Maximal oxygen uptake as a parametric parameter of cardiorespiratory capacity. Med Sci Sports Exerc. 2007;39:103-107.

3. Hill DW, Poole DC, Stevens JC. The relationship between power and the time to achieve VO2max. Med Sci Sports Exerc. 2002;34:709-714.

4. Wilkerson DP, Koppo K, Barstow TJ, Jones AM. Effect of work rate on the functional ‘gain’ of Phase II pulmonary O2 uptake response to exercise. Respir Physiol Neurobiol. 2004;142: 211-223.

Noakes response to Dr Burnley.

Dr Mark Burnley makes an important point. He is correct. No one has the right selectively to analyze data. Whilst I appreciate that this is how what I wrote can be interpreted, that was never my meaning (as should be apparent from the general gist of my argument).

The point I repeatedly make is that the “truth” in exercise science is so often model-dependant since few people actually bother to measure all the variables that comprise their particular model. Thus the basis for the Hill model (which I believe to be incorrect) is the use of oxygen consumption, measured at the mouth, as a surrogate measure of cardiac output and the state of muscle oxygenation during exercise. This model predicts that when the cardiac output reaches its maximum value, (”anaerobic”) conditions develop in the muscle which then cause the termination of exercise. If this is the case, then the cardiac output and hence the oxygen consumption and the state of muscle oxygenation must always be IDENTICAL at exhaustion. If this is not the case, then the model does not explain what is actually causing exhaustion.

So my argument is that if the oxygen consumption is not always exactly the same at exhaustion during maximum exercise testing, then the model has to be rather more complex than is this simple explanation we have inherited from Hill. Better stated, my point was that “submaximal” VO2max values must, according to the Hill model, indicate that exercise terminated before the maximal cardiac output and maximum levels of muscle de-oxygenation were achieved. But since this cannot happen according to the Hill model (since it is these two variables which cause exhaustion), the data are not compatible with his model and thus disprove it. In this sense it is my argument that those data cannot LOGICALLY be included in the analysis if their inclusion modifies the data suffficiently to “prove” a theory with which those specific data are actually incompatible. It was in this sense that I argued that the data should be LOGICALLY excluded from analysis since their inclusion led to the incorrect conclusion. Of course anyone wedded to the Hill model will find it difficult to follow this logic.

Dr Burnley may be one such person for he believes that exhaustion at submaximal VO2 values occurs before the “kinetics drive the VO2 to its maximum’. But how does the Hill model explain such exhaustion? Stating that it occurs because limiting “anaerobic” conditions develop in muscle even before the cardiac output reaches its maximum value is convenient but is ultimately unsatisfactory since it is again a model-dependant explanation. Would it not be better if defenders of this interpretation actually measured cardiac output and skeletal muscle oxygenation and not just their model-dependant surrogate - oxygen consumption at the mouth? The simulaneous measurement of muscle activation would be essential in my view if one wishes to test the alternate (central governor) theory that maximal exercise always terminates before there is 100% activation of all the available motor units in the exercising limbs.

However I am relieved that Dr Burnley does not find fault with the remainder of this quite long review. Does this mean that he accepts the logic of my argument that the regulation of maximal exercise performance must reside in the central nervous system?

Or what does he mean by the loaded phrase “further misleading interpretations from entering the literature”? To which other “misleading interpretations” does he refer?

Mark Burnley’s RESPONSE to Dr Noakes:

I now better appreciate Prof. Noakes’ reasons for using the words he used following his response to my eletter posted on the BJSM Blog, and consider the issue of “data exclusion” settled. However, I would like to make the following points to clarify my position and respond to Noakes’ interpretation of the physiology:

1. I do not consider myself “wedded to the Hill model” because the “Hill model” as presented by Noakes bears no relationship to my understanding of the physiological response to exercise. It is my contention that the “Hill model” is an erroneous caricature of the physiology of exercise that Noakes uses as a straw man in contrast to his central governor model. Few scientists are likely to defend the view that cardiac output and VO2 must always be identical at exhaustion, for the evidence against this proposition is overwhelming! In short, the “Hill model” is not a contemporary model of exercise physiology, it is a vehicle invented by Noakes.

2. “Oxygen consumption” or, more correctly, pulmonary oxygen uptake, is not a “surrogate measure of cardiac output and the state of muscle oxygenation”. To claim this indicates a misunderstanding or misrepresentation of basic physiological measurements. Pulmonary VO2 is useful because in both the non-steady state and the steady state it closely reflects muscle VO2, which itself reflects energetic events occurring in the cell. If one accepts that the rate of energy transfer is an important consideration during exercise, then measuring the most quantitatively significant energy transfer process is worthwhile. Furthermore, the phrase “state of muscle oxygenation” is hopelessly vague. Does Noakes mean “muscle O2 extraction”, “arterio-venous oxygen difference” or “intracellular [or mitochondrial] PO2”? The first two measures are difficult to make, whilst the latter is currently impossible to make during whole-body exercise.

3. I do not “believe” that exhaustion occurs before VO2max is attained during “extreme” exercise, it is an experimental fact: exercise is terminated whilst VO2 is still rising in a futile attempt to meet the energetic demand.[1] Exercise under these conditions is terminated because the subject is no longer able to sustain the power requirements of the task (in my experience not because the subject is unwilling), but this says little of the mechanism. Classic works on the aetiology of muscle fatigue acknowledge that fatigue processes occur at a number of sites within the neuromuscular system,[2,3] and I certainly embrace this. Exhaustion at these “extreme” work rates is attended by falling [PCr] and pH and rising [Pi] and [ADP], amongst other derangements known to cause a fall in tension produced by the myocyte.[4] However, measurements of these processes in whole-body exercise are presently too spatially or temporally crude to be definitive – but that is certainly not a reason to reject the periphery as a plausible or even pivotal contributor to task failure (exhaustion). Note also that the identification of metabolites involved in substrate-level phosphorylation does not imply that the conditions within the cell are “anaerobic”: the concentrations of these metabolites will change progressively during exercise above the so-called “critical power”[5] irrespective of cellular PO2.[6]

4. Noakes argues that the “simulaneous [sic] measurement of muscle activation” is required to test the alternate (central governor) theory “that maximal exercise always terminates before there is 100% activation of all the available motor units in the exercising limbs”. However, this is impossible to verify with current technology. Even if electromyographic recordings are taken from the surface of a large number of muscles and normalised to some measure of maximal voluntary muscle function (such as an MVC), this will not provide an estimate of the fractional number of motor units that are active. The EMG signal is determined, in part, by the number of active muscle fibres in the region of interrogation, their firing frequency, and the conductivity of the tissues between the fibres and the electrodes, not simply by the number of active motor units. A method of determining the total number of active motor units during whole-body exercise would be very useful but does not currently exist.

The processes leading to additional motor unit recruitment during rhythmic whole-body exercise are far from understood. However, it is logical that in conditions where the rate of O2 delivery is maximal (i.e., when cardiac output is maximal) the recruitment of additional motor units will lead to worsening metabolic conditions within the exercising muscles, as those newly recruited fibres will also extract O2 from the microvasculature. The consequent fall in microvascular PO2 will make the appropriate matching of O2 demand and supply (essential for the continuance of exercise) increasingly difficult. Additional motor unit recruitment is thus likely to yield diminishing returns in terms of sustaining the required power output. In this scenario, task failure will occur before all motor units are activated even in the absence of a “governor”.

In summary, Prof. Noakes’ representation of the physiology of exercise could be charitably described as inaccurate. The “Hill model” is not one that any physiologist is “wedded” to because it does not exist. Therein lay the “misleading interpretations” to which I referred in my first letter. One final point needs to be made:

If the “absence of any such catastrophe [myocardial ischaemia or rigor during exercise] suggests the presence of an anticipatory, complex, regulatory control system”[7], then surely the presence of myocardial ischaemia during exercise[8] suggests the absence of an anticipatory, complex regulatory control system? How long can the central governor theory survive with this elephant in the room?

“It does not make any difference how beautiful your guess is. It does not make any difference how smart you are, who made the guess, or what his name is - if it disagrees with experiment it’s wrong. That’s all there is to it.” Richard P. Feynman.

References

1. Hill DW, Poole DC, Stevens JC. The relationship between power and the time to achieve VO2max. Med Sci Sports Exerc. 2002;34:709-714

2. Bigland-Ritchie B, Woods JJ. Changes in muscle contractile properties and neural control during human muscular fatigue. Muscle Nerve. 1984;7:691-699.

3. Gandevia SC. Spinal and supraspinal factors in human muscle fatigue. Physiol Rev. 2001;81:1725-1789.

4. Fitts RH. The cross-bridge cycle and skeletal muscle fatigue. J Appl Physiol. 2008;104:551-558.

5. Jones AM, Wilkerson DP, DiMenna F, Fulford J, Poole DC. Muscle metabolic responses to exercise above and below the “critical power” assessed using 31-PMRS. Am J Physiol Regul Integr Comp Physiol. 2008;294:R585-R593.

6. Richardson RS, Newcomer SC, Noyszewski EA. Skeletal muscle intracellular PO2 assessed by myoglobin desaturation: response to graded exercise. J Appl Physiol. 2001;91:2679-2685.

7. Noakes TD. Peer review/fair review: How did A.V. Hill understand the VO2max and the “plateau phenomenon”? Still no clarity? Brit J Sports Med, in press. DOI: 10.1136/bjsm.2008.046771.

8. Bogaty P, Poirier P, Boyer L, Jobin J, Dagenais GR. What induces the warm-up ischemia/angina phenomenon: exercise or myocardial ischemia? Circulation. 2003;107:1858-1863.

A Reader of the BJSM Blog Asks:

Nitro Patches for Tendinopathy?

I am quite intrigued by this, not only as a physician but more so as a patient with some current injuries. Would you be so kind as to reply with a source that might describe the mechanis(s) of action as well as a link or two to get more detail.

Answer:

Although the precise mechanism is not known, cell culture studies suggest that Nitric Oxide (NO) has a direct stimulating effect on collagen synthesis. For a background to the discussion and direction to the clinical papers on the effectiveness of nitro patches, please see Dr Murrell’s summary in the BJSM Tendinopathy Issue (April 2007).