Response to exercise after blood loss and reinfusion / B. Ekblom, A.N. Goldbarg, B. Gullbring. - (Journal of Applied Physiology 33 (1972) 2 (August); p. 175-180)

• PMID: 5054420
• DOI: 10.1152/jappl.1972.33.2.175

 

Blood doping and erythropoietin. The effects of variation in hemoglobin concentration and other related factors on physical performance / B. Ekblom. - (American journal of sports medicine 24 (1996) 6 Supp (1 November); p. S40-S42)

• PMID: 8947426
• DOI: 10.1177%2F036354659602406S12

Effects of Hemopure on maximal oxygen uptake and endurance performance in healthy humans / M.J. Ashenden, Y. O. Schumacher, K. Sharpe, E. Varlet-Marie, M. Audran. - (International Journal of Sports Medicine 28 (2007) 5 (May); p. 381-385)

• PMID: 17024639
• DOI: 10.1055/s-2006-924365

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Abstract

Haemoglobin-based oxygen carriers (HBOCs) such as Hemopure are touted as a tenable substitute for red blood cells and therefore potential doping agents, although the mechanisms of oxygen transport of HBOCs are incompletely understood. We investigated whether infusion of Hemopure increased maximal oxygen uptake (V.O 2max) and endurance performance in healthy subjects. Twelve male subjects performed two 4-minute submaximal exercise bouts equivalent to 60 % and 75 % of V.O (2max) on a cycle ergometer, followed by a ramped incremental protocol to elicit V.O (2max). A crossover design tested the effect of infusing either 30 g (6 subjects) or 45 g (6 subjects) of Hemopure versus a placebo. Under our study conditions, Hemopure did not increase V.O (2max) nor endurance performance. However, the infusion of Hemopure caused a decrease in heart rate of approximately 10 bpm (p=0.009) and an average increase in mean ( approximately 7 mmHg) and diastolic blood pressure ( approximately 8 mmHg) (p=0.046) at submaximal and maximal exercise intensities. Infusion of Hemopure did not bestow the same physiological advantages generally associated with infusion of red blood cells. It is conceivable that under exercise conditions, the hypertensive effects of Hemopure counter the performance-enhancing effect of improved blood oxygen carrying capacity.

CAS 2005/A/830 G. Squizzato v/ FINA
CAS 2005/A/830 S. v. FINA

• Swimming
• Doping (clostebol)
• Strict liability
• Duty of diligence
• Proportionality of the sanction

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1. Under the FINA Doping Policy, an offence has been committed when it has been established that a prohibited substance was present in the athlete’s body. There is thus a legal presumption that the athlete is responsible for the mere presence of a prohibited substance. The burden of proof lies within FINA and its Member Federation to establish that an anti-doping rule violation has occurred.

2. An athlete fails to abide by his/her duty of diligence if, with a simple check, he/she could have realised that the medical product he/she was using contained a prohibited substance, the latter being indicated on the product itself both on the packaging and on the notice of use. Furthermore, it is indeed negligent for an athlete willing to compete in continental or world events to use a medical product without the advice of a doctor or, at the very least, a physiotherapist. However, if it appears that the athlete had no intention whatsoever to gain advantage towards the other competitors, his/her negligence in forgetting to check the content of the medical product can be considered as mild in comparison with an athlete that is using a doping product in order to gain such advantage. Accordingly, although it cannot be considered that the athlete bears no fault or negligence in such a case, it can be held that he/she bears no significant fault or negligence, which opens the door to a reduced sanction.

3. Substantial elements of the doctrine of proportionality have been implemented in the body of rules and regulations of many national and international sport federations by adopting the World Anti-Doping Code, which provides a mechanism for reducing or eliminating sanctions i.a. in cases of “no fault or negligence” or “no significant fault or negligence” on the part of the suspected athlete. However, the mere adoption of the WADA Code by a respective Federation does not force the conclusion that there is no other possibility for greater or lesser reduction of a sanction.

4. A mere “uncomfortable feeling” alone that a one year penalty is not the appropriate sanction cannot itself justify a reduction of the sanction. The individual circumstances of each case must always hold sway in determining any possible reduction. Nevertheless, the implementation of the principle of proportionality as given in the WADA Code closes more than ever before the door to reducing fixed sanctions. Therefore, the principle of proportionality would apply if the award were to constitute an attack on personal rights which was serious and totally disproportionate to the behaviour penalised.

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In September 2004 the International Swimming Federation (FINA) has reported an anti-doping rule violation against the Athlete Gioriga Squizzato after her sample tested positive for the prohibited substance Clostebol. Consequently on 9 December the FINA Doping Panel decided to impose a 1 year period of ineligibility on the Athlete, starting on the date of the decision.

Hereafter in February 2005 the Athlete appealed the FINA decision with the Court of Arbitration for Sport (CAS). She requested the Panel to acquit her from the charge, or in any event, to reduce the sanction.

The Athlete argued that the violation was non intentional and acknowledged that she had used a cream to her foot as treatment for her skin condition which does not enhance her performance. On this basis, she claimed that she did not commit any fault, nor that she had been negligent.

The Panel finds that the Athlete indeed established how the prohibited substance had entered her system. However she failed to abide by her duty of diligence. With a simple check, she could have realised that the cream was containing a doping agent, as Clostebol is indicated on the product itself both on the packaging and on the notice of use. At least she could have asked her doctor, coach or any other competent person to double-check the contents of the cream bought by her mother.

As the Athlete was effectively suspended from 30 September 2004 onwards, the Panel is of the opinion that fairness requires that the sanction should not last more than one year and should therefore end on September 30, 2005. Therefore, as requested by the Athlete, the commencement of the sanction shall be September 30, 2004 and not December 9, 2004.

On 15 July 2005 the Court of Arbitration for Sport decides that:

1.) The appeal filed by the Athlete is partially upheld.

2.) The decision of the FINA is confirmed with the exception of the commencement of the sanction that shall be September 30, 2004.

(…)

CAS 2009/A/1759 FINA v. Max Jaben & ISA

CAS 2009/A/1778 WADA v. Max Jaben & ISA

CAS 2009/A/1759 FINA vs Max Jaben & Israel Swimming Association

CAS 2009/A/1778 WADA vs Max Jaben & Israel Swimming Association

CAS 2009/A/1759 & 1778 Fédération Internationale de Natation (FINA) & World Anti-Doping Agency (WADA) v. Max Jaben & Israel Swimming Association (ISA)

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• Aquatics (swimming)
• Doping (boldenone and boldenone metabolites)
• Imperative character of the rules establishing deadlines to file an appeal
• Notification of disciplinary decisions to WADA and WADA’s right to appeal
• Presence of a prohibited substance in both samples
• Chain of custody and adverse analytical finding
• Beginning of the suspension period

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1.) It would violate fundamental principles of fairness if procedural deadlines such as the filing deadline in the anti-doping rules of an international federation were to stand at the free disposition of the prosecuting parties especially if the accused athlete remained uninformed of such communications which ultimately affect his procedural rights. Possible erroneous assumptions on jurisdiction cannot be placed at the burden of the athlete and thus an appeal filed beyond the 21-days limit has to be declared inadmissible.

2.) WADA is not obliged to actively and unilaterally enquire about a decision to be issued by a federation in order to preserve its own right to appeal, since this would place an undue burden upon the WADA and possibly hinder the fight against doping. It would require that WADA actively monitor each and every of the hundreds of 1st instance disciplinary decisions on the national level.

3.) So long as a prohibited substance was found to be present in both the A and B sample analyses and was also found to be of exogenous origin, the fact that a second prohibited substance was not present in the B sample does not invalidate the finding of an anti-doping violation on the grounds of the rule “If the sample “B” proves negative, the entire test shall be considered negative and the Competitor, his Member Federation, and FINA shall be so informed”.

4.) Claims of departures from the International Standard for Laboratories and the International Standard for Testing, such as breach of the “chain of custody” in the handling of the samples, remain unsubstantiated if it cannot be established that these alleged violations of the International Standards have caused the adverse analytical finding.

5.) The sanctioned athlete has a right to an expeditious hearing and timely completion of the adjudicative process. So long as the sanctioned athlete has no control over procedural delays and bears no responsibility for them, it is fair and appropriate to deduce the period of delay from the overall period of his provisional suspension.

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In June 2008 the International Swimming Federation (FINA) has reported an anti-doping rule violation against the Israeli swimmer Max Jaben after his A and B samples tested positive for the prohibited substance Boldenone.

On 19 November 2008 the Israel Swimming Association (ISA) decided to impose a 1 year period of ineligibility on the Athlete. This decision was appealed with the ISA High Court of Arbitration. However the High Court dismissed this appeal on 15 December 2008 due to lack of jurisdiction because it involved an international-level athlete.

Hereafter in January 2009 both FINA and WADA appealed both Israeli decisions of 19 November 2008 and 15 December 2008 with the Court of Arbitration for Sport (CAS). WADA requested the Panel to set aside the Israeli decisions and to impose a 2 year period of ineligibility on the Athlete. FINA's appeal was rejected because it was not filed within the set time limit of 21 days. 

The Athlete denied the intentional use of the substance and argued that the test results of the Athens and Cologne Laboratories were contradictory. He asserted that he should be acquitted because of errors and delays in the laboratory procedures, the unsafe chain of custody and the discrepancies in the laboratory findings.

WADA contended that the Athlete had failed to demonstrate how the prohibited substance had entered his system. Also his allegations about the many inconsistencies are without merit.

WADA holds that both the Athens and Cologne Laboratories were WADA-accredited; the Athlete failed to establish any departure from the International Standard for Testing; and his allegations regarding the validity of the IRMS analyses were erroneous.

The Panel finds that the presence of the prohibited substance has been established by the Athens and Cologne Laboratories on the basis of their respective analyses whereas the task of the IRMS analysis was to prove the exogenous origin of the Boldenone metabolite. In the view of the Panel, the Cologne Laboratory confirmed such exogenous origin.

The Panel holds that, apart from the delayed processing of the samples by the Athens and the Cologne Laboratories, the Athlete’s claims of other departures from the International Standard for Laboratories and the International Standard for Testing remain unsubstantiated.

This is particularly the case with regard to his accusation that the chain of custody in the handling of the samples has been breached. The Athlete does not claim that these alleged violations of the International Standards have caused the adverse analytical finding.

As a result the Panel determines that the presence of Boldenone metabolite in both specimens, which was proved in IRMS testing to be of exogenous origin, is sufficient to support the doping violation.

Therefore the Court of Arbitration for Sport decides on 13 July 2009:

1.) The appeal of the World Anti-Doping Agency against the decisions of the Disciplinary Committee of the Israel Swimming Association dated 19 November 2008 and of the High Court of the Israel Swimming Association dated 15 December 2008 is declared admissible and is partially upheld.

2.) The appeal of the Federation Internationale de Natation against the decisions of the Disciplinary Committee of the Israel Swimming Association dated 19 November 2008 and of the High Court of the Israel Swimming Association dated 15 December 2008 is declared inadmissible.

3.) The decision of the Disciplinary Committee of the Israel Swimming Association dated 19 November 2008 is modified; Mr Jaben is declared ineligible for a period of two (2) years, commencing as of 30 April 2008 without any interruption.

4.) All competitive results achieved by Mr Jaben from 30 April 2008 through 5 June 2008, the date of his provisional suspension, and between the date he resumed competition pursuant to the decision of the Disciplinary Committee of the Israel Swimming Association dated 19 November 2008 until the date of this award shall be invalidated with the consequence that all medals, points and prizes shall be forfeited.

5.) This award is pronounced without costs, except for the non-reimbursable Court Office fee of CHF 500 (five hundred Swis Francs) already paid by each of the Appellants and to be retained by the CAS.

6.) Mr Jaben is ordered to pay to the World Anti-Doping Agency an amount of CHF 1,000 (one thousand Swiss Francs) as a contribution towards the latter’s legal and other costs incurred in connection with the present arbitration.

7.) The Israel Swimming Association is ordered to pay to the World Anti-Doping Agency an amount of CHF 2,000 (two thousand Swiss Francs) all a contribution towatds the latter's legal and other costs incurred in connection with the present arbitration.

8.) Mr Jaben, the Israel Swimming Association and the Federation Internationale de Natation shall bear their own legal and other costs.

9.) All other motions or petitions for relief are dismissed.

Effect of rhEPO administration on serum levels of sTfR and cycling performance / K I Birkeland  1 , J Stray-Gundersen, P Hemmersbach, J Hallen, E Haug, R Bahr. - (Medicine & Science in Sports & Exercise 32 (200) 7 (July), p. 1238-1243)

• PMID: 10912888
• DOI: 10.1097/00005768-200007000-00009

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Abstract

Purpose: We assessed the possibility of using soluble transferrin receptor (sTfR) as an indicator of doping with recombinant erythropoietin (rhEPO).

Methods: A double-blind, placebo-controlled study was conducted with the administration of 5,000 U of rhEPO (N = 10) or placebo (N = 10) three times weekly (181-232 U x kg(-1) x wk-1) for 4 wk to male athletes. We measured hematocrit and the concentration of hemoglobin, sTfR, ferritin, EPO, and quantified the effects on performance by measuring time to exhaustion and maximal oxygen uptake (VO2max) on a cycle ergometer.

Results: Hematocrit increased from 42.7 +/- 1.6% to 50.8 +/- 2.0% in the EPO group, and peaked 1 d after treatment was stopped. In the EPO group, there was an increase in sTfR (from 3.1 +/- 0.9 to 6.3 +/- 2.3 mg x L(-1) , P < 0.001) and in the ratio between sTfR and ferritin (sTfR-ferritin(-1)) (from 3.2 +/- 1.6 to 11.8 +/- 5.1, P < 0.001). The sTfR increase was significant after 1 wk of treatment and remained so for 1 wk posttreatment. Individual values for sTfR throughout the study period showed that 8 of 10 subjects receiving rhEPO, but none receiving placebo, had sTfR levels that exceeded the 95% confidence interval for all subjects at baseline (= 4.6 mg x L(-1)). VO2max increased from 63.6 +/- 4.5 mL x kg(-1) x min(-1) before to 68.1 +/- 5.4 mL x kg(-1) x min(-1) 2 d post rhEPO administration (7% increase, P = 0.001) in the EPO group. Hematocrit, sTfR, sTfR-ferritin(-1), and VO2max did not change in the placebo group.

Conclusion: Serum levels of sTfR may be used as an indirect marker of supranormal erythropoiesis up to 1 wk after the administration of rhEPO, but the effects on endurance performance outlast the increase in sTfR.

Effects of erythropoietin administration in training athletes and possible indirect detection in doping control / M. Audran, R. Gareau, S. Matecki, F. Durand, C. Chenard, M.T. Sicart, B. Marion, F. Bressolle. - (Medicine & Science in Sports & Exercise 31 (1999) 5 (May); p. 639-645)

• PMID: 10331881
• DOI: 10.1097/00005768-199905000-00003

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Abstract

Purpose: This study investigated the effects of repeated subcutaneous injection of rHuEpo (50 IU x kg(-1)) in athletes and proposes a method based on the measurement in blood samples of the sTfR/serum protein ratio to determine if the observed values of this marker are related to rHuEpo abuse.

Methods: Serum erythropoietin concentrations, and hematological and biochemical parameters were evaluated, during treatment and for 25 d posttreatment in nine training athletes. Moreover, the effect of rHuEpo administrations on the maximum oxygen uptake (VO2max) and ventilatory threshold (VT) of these athletes was also studied. Threshold values for sTfr and the sTfr/serum protein ratio were determined from 233 subjects (185 athletes, 15 athletes training at moderately high altitude, and 33 subjects living at >3000 m).

Results: Significant changes in reticulocytes, hemoglobin (Hb) concentration, hematocrit (Hct), sTfr, and sTfr/serum proteins were observed during and after rHuEpo treatment. The maximal heart rate of 177 beats x min(-1) at the beginning of the study was significantly higher than the value of 168 beats x min(-1) after 26 d of rHuEpo administration. Compared with the values measured at baseline, the VT measured after rHuEpo administration occurred at a statistically significant high level of oxygen uptake.

Conclusions: When oxygen uptake measured at the VT was expressed as a percentage of V02 max, the values obtained were also significantly higher. The increased values of Tfr and sTfr/serum proteins, respectively, above 10 microg x mL(-1) and 153, indicated the probable intake of rHuEpo.

TAS 2007/A/1252 FINA c/Oussama Mellouli & Fédération Tunisienne de Natation

TAS 2007/A/1252 Fédération Internationale de Natation (FINA) c. M. & Fédération Tunisienne de Natation (FTN)

CAS 2007/A/1252 FINA vs Oussama Mellouli & Fédération Tunisienne de Natation

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• Natation
• Dopage (Amphétamines – ’Adderall’)
• Négligence significative de l’athlète
• Inadéquation de la réglementation avec les circonstances particulières de l’espèce
• Début de la période de suspension

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1. Pour bénéficier de l’application de l’article DC 10.5.2 du Règlement antidopage FINA (absence de négligence ou de faute significative justifiant une réduction de la suspension), un athlète doit non seulement démontrer comment la substance interdire pénètre son organisme mais aussi qu’il ou elle n’a commis aucune faute ou négligence significative. Selon la jurisprudence du TAS, l’examen de la faute ou négligence significative doit être fait en fonction des circonstances particulières de chaque cas d’espèce. Même en état de stress et de fatigue, un sportif d’élite ne peut totalement occulter de son esprit l’obligation qui est la sienne d’éviter qu’une quelconque substance interdite ne pénètre dans son organisme. Le fait que l’usage de l’Adderall soit de plus en plus fréquent dans les universités d’Amérique du nord ne saurait excuser une telle prise de risque surtout de la part d’un étudiant de division “sport-études” qui évolue de surcroît au plus haut niveau mondial de sa discipline.

2. Exceptionnellement, la sanction prévue par l’application stricte des règles antidopage d’une fédération sportive peut apparaître disproportionnée par rapport au comportement reproché à l’athlète, et non conforme au but – à la fois répressif et éducatif – recherché par lesdites règles. Il serait particulièrement inéquitable de ne pas tenir compte des circonstances particulières de chaque espèce même si la négligence est significative et de sanctionner de la même manière celui qui refuse d’admettre avoir pris intentionnellement des produits à fort pouvoir dopant durant une longue période et qui conteste les résultats pourtant clairs des analyses et l’athlète ayant commis une négligence isolée qui s’inscrit dans le cadre d’un parcours jusqu’ici irréprochable. Il s’agit de faire preuve d’une adéquation entre la faute ou la négligence significative et la sanction dans l’application du système répressif, même si le système lui-même se veut très strict.

3. En cas de délais dans la procédure d’audition ou d’autres aspects du contrôle du dopage non imputables à l’athlète, la période de suspension peut commencer à une date antérieure, pouvant remonter à la date de la collecte de l’échantillon.

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On 8 March 2007 the Disciplinary Committee of the Tunisian Swimming Federation (FTN) decided to impose a reprimand on the Athlete Oussama Mellouli after he tested positive for the prohibited substance Amphetamine.

In this matter the Athlete had admitted the violation, accepted the test result and the provisional suspension. He explained that he had used a tablet (Adderall) at the university to stay awake for his studies.

Hereafter in March 2007 FINA appealed the FTN decision with the Court of Arbitration for Sport. FINA requested to Panel to set aside the FTN decision and to impose a 2 year period of ineligibility on the Athlete.

FINA argued that the Athlete tested positive for a prohibited substance and accordingly he had committed an anti-doping rule violation.

In view of the Athlete's conduct the Panel concludes that his Fault or Negligence was significant in this case. Considering the circumstances the Panel decides on 11 September 2007 to impose a proportional 18 month period of ineligibility on the Athlete starting on the date of the sample collection, i.e on 30 November 2006.

A comparison of the physiological response to simulated altitude exposure and r-HuEpo administration / M.J. Ashenden, A.G. Hahn, D.T. Martin, P. Logan, R. Parisotto, C.J. Gore. - (Journal of Sports Sciences 19 (2001) 11 (November); p. 831-837)

• PMID: 11695504
• DOI: 10.1080/026404101753113778

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Abstract

Concerns have been raised about the morality of using simulated altitude facilities in an attempt to improve athletic performance. One assumption that has been influential in this debate is the belief that altitude houses simply mimic the physiological effects of illegal recombinant human erythropoietin (r-HuEpo) doping. To test the validity of this assumption, the haematological and physiological responses of 23 well-trained athletes exposed to a simulated altitude of 2650-3000 m for 11-23 nights were contrasted with those of healthy volunteers receiving a low dose (150 IU x kg(-1) per week) of r-HuEpo for 25 days. Serial blood samples were analysed for serum erythropoietin and percent reticulocytes; maximal oxygen uptake (VO2max) was assessed before and after r-HuEpo administration or simulated altitude exposure. The group mean increase in serum erythropoietin (422% for r-HuEpo vs 59% for simulated altitude), percent reticulocytes (89% vs 30%) and VO2max (6.6% vs -2.0%) indicated that simulated altitude did not induce the changes obtained with r-HuEpo administration. Based on the disparity of these responses, we conclude that simulated altitude facilities should not be considered unethical based solely on the tenet that they provide an alternative means of obtaining the benefits sought by illegal r-HuEpo doping.

The ergogenic effect of recombinant human erythropoietin on VO2max depends on the severity of arterial hypoxemia / Paul Robach, Jose A.L. Calbet, Jonas J. Thomsen, Robert Boushel, Pascal Mollard, Peter Rasmussen, Carsten Lundby. - (PLoS One 3 (2008) 8 (20 August); e2996)

• PMID: 18714372
• PMCID: PMC2500186
• DOI: 10.1371/journal.pone.0002996

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Abstract

Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO(2)) that unequivocally enhances maximal oxygen uptake (VO(2)max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should be a threshold altitude at which VO(2)max is less dependent on CaO(2). To ascertain which are the mechanisms explaining the interactions between hypoxia, CaO(2) and VO(2)max we measured systemic and leg O(2) transport and utilization during incremental exercise to exhaustion in normoxia and with different degrees of acute hypoxia in eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in systemic VO(2)max observed in normoxia (6-7%) persisted during mild hypoxia (8% at inspired O(2) fraction (F(I)O(2)) of 0.173) and was even larger during moderate hypoxia (14-17% at F(I)O(2) = 0.153-0.134). When hypoxia was further augmented to F(I)O(2) = 0.115, there was no rhEpo-induced enhancement of systemic VO(2)max or peak leg VO(2). The mechanism highlighted by our data is that besides its strong influence on CaO(2), rhEpo was found to enhance leg VO(2)max in normoxia through a preferential redistribution of cardiac output toward the exercising legs, whereas this advantageous effect disappeared during severe hypoxia, leaving augmented CaO(2) alone insufficient for improving peak leg O(2) delivery and VO(2). Finally, that VO(2)max was largely dependent on CaO(2) during moderate hypoxia but became abruptly CaO(2)-independent by slightly increasing the severity of hypoxia could be an indirect evidence of the appearance of central fatigue.