• Blood Doping

    Despite numerous positive tests for performance enhancing drugs in Italy and Spain, there has not yet been a positive test in the English Premier League. Although performance enhancing drugs have never been part of the culture of English football, some notable figures have their suspicions.

    FIFA Medical Committee chairman, Michel D’Hooghe, commented “EPO is now quite commonly used in other sports, and I cannot imagine there is a barrier for EPO around the football field.”

    It has been claimed that weaknesses in the Football Association’s drug-testing system could encourage cheats to believe they would not be caught in England. There is a belief that players should be tested far more regularly. During the 2000-01 season, 1,016 tests were carried out in England, with only 24 of these samples taken after matches and the rest sampled at club training grounds. This contrasts with Italy, where two players from each team are tested after every single match. Also, as blood samples are not routinely taken in England, there is no test for EPO or blood doping.

    So, what exactly is blood doping?

    Blood doping first came to the attention of a wider public following the 1972 Munich Olympics, when a double gold medallist reported he had used the procedure prior to the games. The ergogenic effects of blood doping were to increase maximal oxygen uptake during endurance activities, by increasing the amount of circulating haemoglobin.

    Ekblom (1972) described the procedure explicitly. 1-4 units of an athlete’s blood are removed over a 3-8 week period and stored in a freezer. These stored blood cells are then re-infused to the athlete (autologous transfusion) 1-7 days before the event. This procedure produces an increase of up to 20% in red blood cells and haemoglobin, which remains elevated for about two weeks. The increased haemoglobin level produces an increase in the oxygen carrying capability of the athlete’s circulatory system.

    More recently, some endurance athletes have taken to intravenous injection of recombinant erythropoietin (EPO) to get similar effects to the blood doping method mentioned above. Human erythropoietin is produced naturally by the kidneys. The kidneys release an enzyme – erythrogenin – that transforms plasma globulin to erythropoietin, under conditions of hypoxia (for this reason exposure to altitude has a similar physiological effect). Erythropoietin is a glycoprotein which stimulates erythropoiesis in bone marrow and raises the level of circulating haemoglobin. This has been shown to increase aerobic power (Ekblom and Berglund, 1991) and thus endurance performance. Casoni et al (1993) also demonstrated an increase in the levels of circulating red blood cells and haematocrit.

    In order to understand the mechanism of EPO as an ergogenic aid it is necessary to understand the limiting factors for maximum oxygen uptake during endurance performance. Maximal oxygen uptake (VO2max) was first defined by Hill et al (1922) who stated:

    1. There is an upper limit to oxygen uptake
    2. There are interindividual differences in VO2Max
    3. A high VO2 Max is prerequisite in endurance performance
    4. VO2max is limited by the cardiorespiratory system to transport O2 to the muscles.

    Bassett and Howley (2000) described four limiting factors of VO2Max. They were:

    1. Pulmonary diffusing capacity
    2. Cardiac output
    3. Oxygen carrying capacity
    4. Skeletal muscle limitations

    The first three can be described as central limitations and the fourth peripheral. It is the third of these which is affected by EPO and haemoglobin levels. The use of recombinant EPO has been shown to increase VO2max (Ekblom and Berglund 1991).

    Haemoglobin is the iron containing globular protein. Each of the four iron atoms in the haemoglobin molecule can loosely bind one molecule of oxygen, in the following reversable reaction:

    Hb4 + 4O2 produces Hb4O8

    This reaction is not enzyme mediated and relies entirely on the partial pressure of oxygen in solution. When this oxyhaemoglobin reaches the skeletal muscle during exercise the oxygen leaves the red blood cells for consumption by the tissues.

    The classical equation for an exergonic oxidative metabolic process is the aerobic oxidation of glucose – respiration:

    C6H12O6 + 6O2 gives 6CO2 + 6H2O + ATP

    The potential energy within the ATP molecule is utilized for all the energy requiring processes of the cell.

    During endurance exercise at a steady pace (or even vigorous exercise which lasts more than several minutes duration), aerobic reactions provide the important final stages for energy transfer. A graph of oxygen uptake over time would show an exponential rise in the first few minutes, followed by a plateau. This represents the steady state which reflects the balance between energy required by working muscles and ATP production.

    As the workload is increased there is a rapid increase in oxygen uptake, which is directly proportional to exercise severity. The region of the graph where oxygen uptake plateaus, and shows no further increase with an additional workload, is called maximal oxygen uptake, or VO2max. Additional work is accomplished via energy transfer reactions of glycolysis with a resultant formation of lactic acid. Exhaustion follows and the athlete can not continue.

    VO2max quantitively expresses a person’s capacity for resynthesis of ATP. This means it is an important factor in determining a person’s ability to sustain high intensity exercise. A high VO2max is dependent upon, not only increased levels of haemoglobin but also, an integrated response from physiologic support mechanisms, namely blood volume and cardiac output; peripheral blood flow; aerobic metabolism; and pulmonary ventilation. It is difficult to know where to begin in a system that is so well integrated.

    As we are concerned with modification of VO2max during physical performance, it seems appropriate to observe pulmonary ventilation first. Ventilation increases during maximal exercise leading to improvements in maximal oxygen uptake. The tidal volume becomes larger and breathing frequency is reduced. As a consequence, air remains in the lungs for a longer period of time between breaths and there is an increased extraction of oxygen from inspired air.

    During endurance exercise individuals tend to overbreathe in relation to oxygen uptake. Even during maximal exercise, a considerable breathing reserve exists because minute ventilation represents only bout 60-80% of a person’s maximum capacity for breathing (Blomqvist et al 1982). This would indicate that pulmonary ventilation is not usually a weak link in the normal oxygen transport system and that it has slack in the system which can utilise the extra oxygen carrying capacity which results from EPO abuse.

    The next component of the oxygen delivery system fulfills the role of cardiac output and blood volume. Following EPO abuse, the increase in haematocrit and blood viscosity will put increased strain on cardiac function. During maximal exercise, the saturation of haemoglobin with oxygen is very high in percentage terms, so the most effective method of increasing oxygen to the tissues in normal conditions is to increase stroke volume.

    There is a strong correlation between cardiac output and VO2max (Saltin, 1969). This pheneomenom doesn’t take place in isolation and is closely associated with changes in peripheral blood flow. If it did take place in isolation, cardiac output would have to increase 20 fold to sustain the VO2max of top endurance athletes. In addition to this increase there is an increase in the arterial – venous O2 difference which increases the amount of O2 extracted from the blood during exercise. The maximal arterial – venous O2 difference that can be achieved during exercise – is influenced by the body’s capacity to divert a large proportion of blood to the working muscles.

    Certain tissues can temporarily compromise their blood supply by shunting. This redirection can be facilitated by training (Musch, 1987). Lash et al (1995) demonstrated enhancements in the microcirculation of skeletal muscle due to training. By increasing haemoglobin via EPO abuse, the drive of cardiac output can be decreased and may lead to decreased cardiac output. This would decrease blood flow and lead to a decrease in peripheral oxygen, and actually decrease aerobic capacity.

    Aerobic metabolism is the final component examined here, which plays a part in the determination of VO2max. This occurs within the mitochondria when the pyruvate molecule is irreversibly converted to a form of acetic acid. This compound then enters the second stage of carbohydrate utilization known as the Krebs cycle. The most important function of the Krebs cycle is the generation of electrons (hydrogen) for transfer to the respiratory chain. Under normal conditions the transfer of electrons and subsequent release of energy are tightly coupled to ADP phosphorylation.

    Endurance training improves the metabolic capacity of the trained muscle. More specifically, the mitochondria enlarge and even increase in number, as does the quantity of enzymes for aerobic energy transfer (Holloszy and Coyle 1984). There is also increased muscle capilliarization – this is 40% greater in trained athletes (Brodal et al 1976). If the increase in an athlete’s VO2max is largely due to EPO abuse, and subsequent increases in haemoglobin levels, then the cellular adaptations mentioned here will not be sufficient to gain fully from the oxygen carrying capacity.

    Apart from the fact that it is an unfair and unethical practice, EPO use can also be extremely dangerous. The exact effect and rate of erythropoiesis mediated by recombinant EPO is unknown. Large increases in haematocrit can lead to dangerous increases in blood viscosity. This greatly increases the likelihood of a stroke or heart attack, heart failure and pulmonary oedema. For this reason the Internationl Olympic Comittee (IOC) have placed recombinant EPO on the banned substance list. However, because it is a naturally occurring substance it’s detection is very difficult.

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