Biology 105
Biology of Exercise
Spring 2003

4/23/03 - Pre-class outline

Learning objectives:

How does blood doping work?

Why is it illegal?

Diagrams

• Controversy over termination of drug trial (external site)
• Hyponatremia fact sheet (external site)
• Capillary function
• World Anti-Doping Agency (external link)

• Blood doping

• Original blood doping techniques involved adding red blood cells to an athletes blood
• Removal of red blood cells and reinfusion (several weeks later) can lead to an increase in RBC concentration in the blood.
• Reinfusion of two units of blood (about 900 ml) can produced substantial increases in blood hemoglobin (about 8%) and VO2max (about 4%).  The mechanism is that increased RBCs leads to increased blood carrying capacity for oxygen, and thus to increased delivery of oxygen to the tissues per volume of blood.
• Performance gains are less consistent than hemoglobin gains.
• The reinfusion process could was a bit awkward to perform, and could sometimes be detected by authorities, making it difficult to use as a performance enhancer.
• Interestingly, training at altitude can also produce increased RBC levels.
• More recently, doping has been achieved by using recombinant human erythropoetin.  (rhEPO)
• EPO is a hormone released by the kidney in response to hypoxia (low oxygen levels)
• EPO stimulated the synthesis of RBCs
• rhEPO is a form of EPO that is synthesized artificially.  It can be mass produced, and can not be chemically differentiated from a person's own EPO.
• Should athletic associations prohibit EPO use?
• The general consensus is yes.
• It gives unfair advantages to some competitors.
• It is potentially dangerous.  High levels of RBCs can increase blood viscocity, leading to dangerous acute increases in blood pressure.  When this happens in the lungs, increased blood pressure in the pulmonary capillaries can lead to fluid filtration out of the capillary into the lung.  This is called pulmonary edema and can lead to impaired oxygen transport.
• Nonetheless, EPO use is thought to be widespread, and recently was found to be very common among competitive cyclists.
• But how to detect EPO?
• Three problems
• We all already have EPO in our blood.
• An exposure to EPO can lead to RBC synthesis that will last for weeks, long after traces of the EPO are gone.
• Manipulations other than taking EPO can increase blood EPO concentration and can increase blood RBC levels.  Altitude exposure is the best  example.
• Original rules to limit EPO use were based on a Hct cutoff.  For example, if more than 47% of the blood was RBCs, then the person was disqualified.
• This was obviously not the best mechanism for discouraging use, and could disqualify folks who trained fairly (i.e. at altitude).
• In fact, some argued that the rule could encourage folks to use EPO to get to the 47% Hct limit.
• Furthermore, it is possible to manipulate Hct levels with saline infusions and other interventions.
• There is hope.
• Recent studies have focused on defining the overall response of the body to EPO.
• These studies (i.e. Parisotto et al, 2000) look at Hct, blood EPO, immune cell counts, RBC precursor (reticulocyte) levels, and other variables (soluble transferrin receptors).  (Transferrin is a blood protein that binds and carries iron.)
• By defining an overall profile of changes that occur with EPO use rather than focusing on a single factor, it is thought that more accurate detection can occur.