Blood doping
Blood doping is defined as the use of illicit products (e.g. erythropoietin (EPO), darbepoetin-alfa, hypoxia-inducible factor (HIF) stabilizers) and methods (e.g. increase aerobic capacity by maximizing the uptake of O2) in order to enhance the O2 transport of the body to the muscles.
[2] The body undergoes aerobic respiration in order to provide sufficient delivery of O2 to the exercising skeletal muscles and the main determining factors are shown in figure 1.
Erythropoietin (EPO) is a glycoprotein hormone produced by the interstitial fibroblasts in the kidney that signal for erythropoiesis in bone marrow.
The increased activity of a hemocytoblast (RBC stem cell) allows the blood to have a greater carrying capacity for oxygen.
[4] Because of its physiological side effects, particularly increased hematocrit, EPO has become a drug with abuse potential by professional and amateur cyclists.
Myo-inositol trispyrophosphate (ITPP), also known as compound number OXY111A, is an allosteric effector of hemoglobin which causes a rightward shift in the oxygen–hemoglobin dissociation curve, increasing the amount of oxygen released from red blood cells into surrounding tissue during each passage through the cardiovascular system.
[12] The freezing process, conversely, limits the aging of the cells, allowing the storage of the blood for up to 10 years with a 10% to 15% loss of RBCs.
Nearly 50% of autologous donations are not used by the donor and are discarded, as current standards do not allow transfusion of these units to another patient for safety reasons.
[citation needed] Biochemical and biotechnological development has allowed novel approaches to this issue, in the form of engineered O2 carriers, widely known as "blood substitutes".
The blood substitutes currently available are chiefly polymerized haemoglobin solutions or haemoglobin-based oxygen carriers (HBOCs) and perfluorocarbons (PFCs).
Chemical methods developed to overcome this problem have resulted in carriers that effectively release oxygen at the physiological pO2 of peripheral tissues.
Recent developments have shown that HBOCs are not only simple RBC substitutes, but highly effective O2 donors in terms of tissue oxygenation.
PFCs are substantially clear and colorless liquid emulsions that are heterogeneous in molecular weight, surface area, electronic charge, and viscosity; their high content of electron-dense fluorine atoms results in little intramolecular interaction and low surface tension, making such substances excellent solvents for gases, especially oxygen and carbon dioxide.
Since PFCs dissolve rather than bind oxygen, their capacity to serve as a blood substitute is determined principally by the pO2 gradients in the lung and at the target tissue.
[24] Transition metal complexes are widely known to play important roles in erythropoiesis; as such, inorganic supplementation is proving to be an emerging technique in blood doping.
[25] The signaling pathway that induces erythropoietin secretion and subsequently red blood cell manufacture using cobalamin is O2 dependent.
In addition to N-terminus binding, it has also been hypothesized that replacement of Fe2+ by Co2+ in the hydroxylase active site could be a contributing factor to the stabilizing action of Co2+.
[29] Autologous blood doping detection is done indirectly via CO rebreathing technique to measure the nonphysiologic increases in Hb mass.
Second step, CE separation is done under certain condition, in this case background electrolyte consisting of ammonium formate (75mM at pH 9.5) in order to provide sufficient resolution between HBOC and Hb.
Fourth step, time-of-flight or mass spectrometer allowed increased accuracy in selectivity between hemoproteins and other proteins and definite determination of HBOC uptake.
[33] As early as 1947, military research scientists were studying ways to increase fighter pilots' tolerance for hypoxia at high altitude.
In one such study, red blood cells were transfused into ten males at the US Naval Research facility, resulting in increased oxygen capacity.
Senior nutritionist at the Australian Defence Science and Technology Organisation Chris Forbes-Ewan is quoted as saying that, unlike in sport, "all's fair in love and war".
[38] Cyclist Joop Zoetemelk admitted to receiving blood transfusions during the 1976 Tour de France, where he finished second, although he claimed that these were intended to treat his anaemia rather than enhance his performance.
[39][40] In the same year cyclist Francesco Moser used blood transfusions to prepare for his successful attempt to break the hour record.
Cyclist Tyler Hamilton failed a fluorescent-activated cell sorting test for detecting homologous blood transfusions during the 2004 Olympics.
[41] Tour de France rider Alexander Vinokourov, of the Astana Team, tested positive for two different blood cell populations and thus for homologous transfusion, according to various news reports on July 24, 2007.
[48] In September 2010, the Swiss Federal Supreme Court rejected the athlete's appeal, stating that Pechstein's inherited blood anomaly had been known before.
[49] On May 20, 2011, Tyler Hamilton turned in his 2004 Olympic Gold Medal to the U.S. Anti-Doping Agency [50] after admitting to doping in a 60 Minutes interview.
He later admitted to using banned substances including blood doping with transfusions and EPO in an interview with Oprah Winfrey on January 17, 2013.
