Blood Boosting. 2006 – Prohibited Methods M1. Enhancement of Oxygen Transfer Blood doping,...
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Transcript of Blood Boosting. 2006 – Prohibited Methods M1. Enhancement of Oxygen Transfer Blood doping,...
Blood Boosting
2006 – Prohibited MethodsM1. Enhancement of Oxygen Transfer
• Blood doping, including the use of autologous, homologous, or heterologous blood or red blood cell products of any origin.
• Artificially enhancing the uptake, transport or delivery of oxygen, perfluorochemicals, efaproxiral (RSR13) and modified Hb products
Blood Boosting
• Oxygen delivery vital for aerobic exercise• Determined by total body Hb• Blood boosting/doping – techniques employed to
augment O2 carrying capacity• Includes:
– Blood transfusion;– Endogenous stimulation of rbcs via legal altitude
training, hypoxic tents, EPOs, EPO gene therapy, or EPO mimetics;
– Blood substitutes eg. Modified Hb solutions and perfluorochemicals
Blood Transfusion
• Blood units removed, RBC harvested, stored, later reinfused
• Notable Finnish and Italian distance runners have admitted use
• US cyclists at 1984 Olympics• Improved performance is
immediate• Buick et al., (1980), reinfusion
elevated Hb, VO2max and run time to exhaustion
• 10km running >1min faster, improvement lasted for at least 2 weeks
Blood Boosting
Blood Boosting
Erythropoiesis
• Skull, bony thorax, vertebrae, iliac crests, upper ends femur and humerus.
• Controlled by circulating levels of EPO
• Stimulus is reduced O2 delivery to kidney ie. Altitude, anaemia
• Net effect is ↑number of rbc’s and rate of release into circulation.
EPO• Recombinant DNA techniques
rHuEPO– rHuEPO-α, rHuEPO-β – rHuEPO-ω (lower doses needed) and
Darbepoietin-α (Aranesp)– Dynepo (EPO produced by human stem
cells)• Recombinant EPO (r-HuEPO) used
tx renal failure• Admin subcutaneously or iv
– Oral forms being developed encapsulated in liposomes
– Subcutaneous encapsulated forms• Same effect as altitude but are able to
maintain training intensity.
EPO• Raises Hct to abnormally high levels and increases Fe
requirement;• ↑bp and viscosity - ↑risk thrombosis and stroke;• Long-term - LV hypertrophy and ultimately heart failure;• Blunted endogenous EPO response severe anaemia;• Development of anti-EPO antibodies• Deaths of 18+ cyclists – rumoured to be EPO abuse;• Does it work?
– Most studies on unhealthy– Audran et al., (1999) 9 athletes, rHuEPO (50IU.kg-1) 26d. Tx
stopped if Hct>50%. • ↑Hct, Hb, VO2max (8.5%), and VO2 at VT.• All ↑ aerobic power
• Marion Jones? Power events?
EPO and Environmental Stress
• Altitude– Brief studies (<1hr) in hypobaric chamber
• Pace et al., (1947) lower hr;
• Robertson et al., (1982) less reduction in VO2max.
– Longer stays at altitude• Young et al., (1996) – no diff in decline VO2max or
performance
– Ergogenic effect may diminish as altitude increases;
– Ergogenic effect may only be apparent with acute hypoxic exposure.
EPO and Environmental Stress
• Heat– Magnitude of ↑Tc related to relative exercise
intensity;– Also blood doping may allow O2 requirements
to be met with lower blood flow – alleviating competition between muscle and skin;
– Studies by Sawka et al., (1987/8/9) support thermoregulatory advantage
– But dehydration will exacerbate ↑ viscosity
EPO Mimetics
• Interest in identifying active peptide domains of EPO;
• Synthesise derivatives• Discover nonpeptide small mimetics with
resistance to proteolytic digestion, good permeability, oral admin.
• Xenobiotics – so easy to detect– But short half life may pose detection problem
Testing - EPO
• 1990 IOC added to banned list;• XC skiers and [Hb]• UCI ’97 – Hct 50% – banned for 15 days for
health• Hard evidence ’98 with Voet/Festina affair• 1st test Sydney – blood and urine• Difficult to test – short plasma ½ life, close
homology between endogenous and recombinant EPO
Blood Substitutes
• Used due to risk of eg. CJD with homologous/heterologous blood;
• Perfluorocarbons (PFC’s) and Hb based oxygen carriers (HBCO’s);
• PFC’s are highly fluorinated inert organic compounds that can dissolve large volumes of oxygen (Lowe, 2001). Unreactive and excreted as a vapour by exhalation;
• Exchange gases more rapidly/completely than rbc’s – but require high %s of inspired oxygen
Blood Substitutes
• HBOC’s are x-linked (↓ O2 affinity & stabilises molecule so reduces renal toxicity) or microencapsulated Hb molecules;
• Right shifted sigmoidal Hb-oxygen dissociation curve;• Hughes et al.,(1995)- performance similar to autologous
blood transfusion• One near fatal suspected case with Swiss cylcist in ’98• 2001 Giro d’Italia – an HBOC (Hemassist) found in hotel
room of Italian cyclist
Allosteric effectors of Hb
• Bind reversibly to Hb, decrease oxygen affinity• Eg. RSR13 (effraproximal sodium) – used in tx
brain tumours, and has potential in conditions with tissue hypoxia (eg. Cardiovascular events)
• Mimics effect of 2,3-BPG – shifts O2-dissociation curve to the R ;
• Effect lasts 3-6 hours after iv infusion – but manufacturer reports sensitive and validated methods of detection in blood/urine.
RSR-13 (Right Shifting Reagent)
0
0.1
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0 20 40 60 80 100 120 140 160 180 200
Oxygen partial pressure (mm Hg)
Fra
cti
on
al
sa
tura
tio
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Neutral pH
Acid pH
Acid pH in tissue promotes oxygenrelease
Tricks haemoglobin to deliver more oxygenClinically used to increase tissue pO2 prior to tumour radiation therapy
Plasma Expanders
• Hydroxyethyl starch (HES, HespanTM)
• Expands plasma for 24 hrs, but detected for 17 – 24 weeks
• Masks a raised Hct.
• Side effects – increased coagulation
• Finish XC skier tested +ve 2001.
Refs
• Gaudard et al., (2003) Drugs for increasing oxygen transport and their potential use in doping. Sports Med. 33(3): 187 – 212
• Sawka et al., (1996) ACSM Position Stand: The Use of Blood Doping as an Ergogenic Aid. MSSE 28(10) 127 - 134