The Procedure of Blood Doping
Buick et al (Wilmore, 1994) have shown that 900ml is the minimum amount of whole blood that must be removed from the individual and later re-infused if such increases in VO2max, and so performance, are to be observed. If smaller amounts are used, there may be no difference at all. Freezing is used to store the erythrocytes, allowing almost unlimited storage time, and only about 15% of the red blood cells are lost (Wilmore, 1994), as opposed to the 40% lost on refrigeration. Prior to freezing, the withdrawn blood is centrifuged, and the removed erythrocytes are mixed with glycerol at a haematocrit of 90% (Gledhill, 1992). When the individual is ready for re-infusion, a week before competition, the erythrocytes are thawed and deglycerolised, and reconstituted with physiological saline to a haematocrit of 50% (Gledhill, 1992), the same haematocrit level as seen in normal blood. The transient increase in blood volume that occurs on re-infusion, with no rise in haematocrit, is responded to by loss of surplus fluid, restoring the normal blood volume and thereby causing the desirable increase in haematocrit and haemoglobin concentration. If successful, there will be a substantial increase in haemoglobin content. There is a critical period of 6-10 weeks before re-infusion (Wilmore, 1994) if the process is to be successful, as the body must be allowed time to restore the blood’s haematocrit to pre-withdrawal level. If these criteria are met, substantial increases in VO2 max, and so endurance, are seen.
The momentary hypervolemia that occurs after blood doping is most likely too short-lived to affect athletic performance due to increased strain on the heart. Blood flow velocity is contrariwise correlated to viscosity. An exponential increase in blood viscosity (Thomas, 1988) transpires with a haematocrit in excess of 50%. An upsurge in viscosity may lead to a concomitant reduction in venous return and cardiac output, and an ensuing decline in the amount of oxygen available to the muscle. It is imperative that the extra erythrocytes infused into the blood be of appropriate quantity to attain the maximal benefits to athletic performance, with none of the associated modifications in vasculature brought about through altered viscosity. Animal studies by Guyton et al (Jones, 1989) have shown that the transient increase in blood and stroke volume and cardiac output is responded to through compensatory mechanisms to reverse these effects. As a result of the transient hypervolemia, and the rise in pressure within the capillary, plasma transudation and loss of blood plasma (Jones, 1989) are initiated, which safeguards against artificial endeavours to increase blood volume. This plasma efflux restores normal blood volume, so the concentration of haemoglobin and the amount of oxygen in the blood are increased. The amount of oxygen presented by the left side of the heart rises, as too does the maximal threshold of oxygen withdrawal by the exercising muscle.
The Use of Erythropoietin in Blood Doping
Erythropoietin is an endogenous hormone produced by the kidney that stimulates erythrocyte production in the bone marrow (Wilmore, 1994). Erythropoietin has been shown to increase erythrocyte production in altitude training; at lower partial pressure of oxygen (Wilmore, 1994), erythropoietin release is stimulated (figure 1). That erythropoietin has been shown to vastly increase the haematocrit level of renal failure patients (Wilmore, 1994) led to the suggestion that it could be used to achieve the same end in athletes, and recombinant DNA techniques have led to the cloning of human erythropoietin. The premise behind its use, similar to that of blood doping, is that a rise in erythrocyte concentration will cause a subsequent increase in the amount of oxygen carried in the blood (figure 2). The effect of erythropoietin on oxygen capacity is illustrated through experiments on the effect of injecting low doses of rHuEPO on performance endurance and VO2max. Six weeks after erythropoietin administration (Wilmore, 1994) haemoglobin concentration and haematocrit increased by 10%, VO2max increased 6% to 8%, and time to exhaustion increased 13% to 17% (Wilmore, 1994). These results were accredited to the enhanced erythrocyte, and hence haemoglobin, mass.
Figure 1: The positive and negative effects of rHuEPO administration to the athlete.
Figure 2: The regulation of erythropoietin stimulation in the body. EPO is produced in response to the amount of oxygen available to the tissue. If the tissue is not receiving enough oxygen, the ensuing hypoxic state stimulates the production of EPO, and thus erythrocytes. Conversely, if the tissue is in a hyperoxic state, the production of EPO is attenuated.
A number of advantages can be seen in the use of rHuEPO when compared with traditional blood doping techniques. The administration of rHuEPO is much easier and more effective; indeed, the athlete may perceive an instantaneous increase in energy after rHuEPO administration. Furthermore, traditional blood doping causes an increase in erythrocyte concentration that is only sustained for a few weeks. Conversely, rHuEPO administration causes a rise in erythrocyte mass that takes several weeks to accomplish, but that is sustained for the duration of rHuEPO treatment.
The Physiological Advantages of Blood Doping
Unarguably, blood doping conveys beneficial effects to the endurance athlete (figure 3). Each gram of haemoglobin has the capacity to carry 1.34ml of oxygen. So, an increase of 2g/100ml in haemoglobin concentration may cause a subsequent rise in the capacity of the blood to carry oxygen by approximately 25ml for every 1000ml of blood. In effect, assuming the increase in blood viscosity would not have an adverse effect on the heart, this would mean that at a cardiac output of 24 litres per minute, 300ml of extra oxygen (Jones, 1989) is provided at the muscle each minute. The increase in haemoglobin concentration translates to a 5 to 13% increase in aerobic capacity, reduced submaximal heart rate and blood lactate for a standard exercise task (McArdle, 1996), and an increased endurance capacity. Whilst blood doping may cause an improved endurance capacity of up to 25%, the enormity of improvement in endurance capacity is somewhat influenced by the preliminary physical fitness of the individual. Those moderately fit are more likely to experience a vaster increase in VO2max compared with those individuals who are either more, or indeed less, fit. In addition to its function in increasing the oxygen-carrying capacity of the blood, blood doping improves thermoregulation, partly through promoting enhanced sweating responses, and buffering of lactic acid.
Figure 3: A graph to show the improvements in running times for distances of up to 11km following blood doping (Wilmore, 1994).
One of the principle functions of the blood is to transfer heat from the exercising muscle and away from the body core, so to keep any increase in body temperature to a minimum. In addition to its role in oxygen transfer, a considerable fraction of the cardiac output is concerned with thermoregulation. An increased haematocrit translates to a somewhat less significant fraction of the cardiac output being requisite in carrying oxygen to the exercising muscles, so more blood can be focussed on thermoregulation. This increase in heat dissipation to the skin reduces any performance limitation resulting from increased temperature.
During exercise, the working muscles use up the oxygen in the body; this decline in oxygen means the muscles cannot then achieve their full capability. This oxygen debt stimulates the production of lactic acid, which leads to pain within the muscle tissue, and fatigue. The contractibility of exercising muscle is limited through lactic acid accretion through its inhibitory effects on the muscle enzymatic systems. The circulatory system is a principle acid/base buffering system in the body, with 70% of the buffering is regulated by haemoglobin. Increased erythrocyte concentration allows more lactate buffering, so the athlete can maintain a normal pH value for longer, and so endure more anaerobic exercise before the enzymatic systems of the muscle are inhibited through elevated concentration of acid.
At the time of blood withdrawal, the athlete is unable to train, negating several of the upshots accomplished through the procedure. Critical regulatory factors include the amount and timing of erythrocyte infusion. Haemoglobin and haematocrit are reduced for up to 2 weeks following withdrawal, but have returned to pre-withdrawal levels by 6 weeks. If the erythrocytes are re-infused before this critical time period has elapsed, and a return to normal values for haemoglobin and haematocrit has not been accomplished, there would be a reduction in the level of polycythemia achieved. On re-infusion, haemoglobin and haematocrit levels have been shown to increase 8% over 24 hours and 11% after 1 week (Thomas, 1988). The ensuing 15 weeks effect a linear decline to pre-withdrawal, values (figure 4).
Figure 4: (McArdle, 1996) A graph to show the changes in haemoglobin concentration that occur on blood doping.
The Physiological Disadvantages of Blood Doping
The prospective profits of blood doping are over-shadowed by the associated underlying dangers. Blood doping has the potential to produce effects contradictory to those expected. A sizeable increase in erythrocyte, and thus cellular, concentration may cause a rise in blood viscosity. In turn, this may lead to a diminution in cardiac output, causing impaired blood flow, and so less oxygen is available at the periphery. This subsequently causes a decline in aerobic capacity. An increase in blood viscosity causes a concomitant increase in vascular resistance, necessitating more dynamic contraction of the heart to pump the blood around the body. The extra burden placed on the heart may result in a large number of problems, such as intravascular clotting, and possible heart failure. Indeed it is suggested that a number of deaths among competitive cyclists (Wilmore, 1994) in the 1990s were due to the use of erythropoietin, although this proposition has not been verified.
After competing in an endurance event, the athlete may naturally be subjected to an increased haematocrit due to loss of fluid, achieving a resultant haematocrit of roughly 55%. Any additional increase above this amount places the athlete at considerable risk to toxic reaction. Thus if this athlete has previously received rHuEPO injections, causing a pre-event haematocrit of 50-55%, post-event the haematocrit would exceed 65%, placing him in considerable danger of such a reaction. These thromboembolic complications are brought about through the enhancing effect of erythropoietin on endothelial activation and platelet reactivity (Cazzola, 2001), particularly in those genetically predisposed to such problems. In those athletes, while few, that do incur these problems, there may be considerable handicaps for the remainder of their life, or worse still they may die from erythropoietin abuse. Animal studies using rats have illustrated the detrimental effects of erythropoietin abuse. Termination of acute rHuEPO use is succeeded by a potent blockage of erythropoietic activity with secondary anaemia (Cazzola, 2001). Such an outcome is attributable to intrinsic erythroid marrow exhaustion (Cazzola, 2001), specifically involving the erythroid progenitors. Experiments involving overexpression of erythropoietin in mice have shown resultant cardiac dysfunction and untimely death.
Whilst the technique is reasonably anodyne if carried out under medical supervision, there are intrinsic risks associated with blood doping. A careless mis-labelling of the withdrawn blood places the athlete at risk of contracting hepatitis or acquired immune deficiency syndrome (AIDS). With regard to rHuEPO administration, constant supervision of the individual’s haematocrit and blood pressure, and any necessary fine-tuning of the dosage and frequency of administration to forestall toxic reactions, is essential. Such toxic reactions include seizures, a decrease in blood flow velocity, clotting, and an hypoxic internal environment. In the most severe cases, the athlete may experience conditions such as pulmonary embolism or myocardial infarction, which could be fatal.
The direct effects of erythropoietin use are not as foreseeable as those of erythrocyte re-infusion, as on injection of the drug into the body, the amount by which erythrocyte production will be stimulated is erratic. The dosage of rHuEPO required to see the desirable increase in haematocrit vary substantially between individuals. As its effects vary from person to person, it is vital that the use is properly regulated. Without efficient regulation of its use, athletes may be tempted to use sequentially higher doses to increase performance. These higher doses administered over long periods increase the likelihood of toxic reaction. Although erythropoietin is removed from the liver within a day of administration, its effects may still be apparent for 2 to 3 weeks, and the consequence of excessive dosage may not be noticeable in time to be treated.
Conclusion
The International Olympic Committee has ruled “any blood doping procedure used in an attempt to improve athletic performance is unethical, unfair, and exposes the athlete to unwarranted and potentially serious health risks”(Verbruggen, 2001). The problem is that, at present, it is impossible to determine with absolute certainty that an athlete is using blood doping. Its undetectability renders blood doping a very attractive option to the dishonest athlete. Who is to define what signifies an unnaturally high erythrocyte concentration? It is also impossible to prove that the abnormally high erythrocyte concentration is due to blood doping, and not training at high altitude. However, given the inherent dangers associated with the use of rHuEPO by competitive athletes, it is imperative that effective tests to determine whether it has been used are developed. The development of such tests should focus attention to features of the erythrocytes, including their distribution and haemoglobin and haematocrit levels, and characteristics of the reticulocytes and macrocytes.
The athlete will forever be looking for ways to improve performance. This is not a characteristic that is peculiar to the world of sport, rather it reflects the trend in our society (Verbruggen, 2001). Every means is justified to achieve the desired ends. The development of the “sleep chamber” allows athletes a way to improve their erythrocyte concentration through permissible and harmless means. The chamber apes the decreased air pressure of high altitudes, so causing an increase in erythrocyte production. Controlled use of this procedure may potentially increase the haemoglobin concentration by in excess of 23%. This process, and that of high altitude training, offers the endurance athlete a way of improving performance without resorting to unethical, illegal, and potentially very dangerous, measures.
Word count: 2786
References:
[1] Jones M, Tunstall Pedoe DS (1989) Blood Doping – a literature review. British Journal of Sports Medicine 23 (2) p.84-88
[2] Wadler GI, Hainline B (1989) Drugs and the Athlete. F.A. Davis Company, USA. P.172-177
[3] Verbruggen, H (2001) The EPO Epidemic in Sport. ISLH XIVth International Symposium p. 20
[4] Cazzola, M (2001) Erythropoietin Pathophysiology, Clinical Uses of Recombinant Human Erythropoietin, and Medical Risks of Its Abuse in Endurance Sports. ISLH XIVth International Symposium p.21-22
[5] Thomas, JA (1988) Drugs, Athletes and Physical Performance. Plenum Publishing Corporation, New York. P.147-167
[6] McArdle WD, Katch FI, Katch VL (1996) Exercise Physiology – Energy, Nutrition and Human Performance. 4th edition. Williams and Wilkins. P. 465-467
[7] Gledhill N, Warburton D (1992) Haemoglobin, Blood Volume and Endurance in The Encyclopedia of Sports Medicine Endurance in Sport ed: Shephard and Astrand. 2nd edition. Blackwell Science. P. 423-437
[8] Wilmore JH, Costill DL (1994) Physiology of Sport and Exercise. Human Kinetics. P. 338-344.
