Enhanced RBC mobilization
Upon exercise, the horse's spleen contracts, adding a significant amount of red blood cells into the central circulation to
meet the demand of maximal exercise. Maximal oxygen uptake (VO2max) in the horse is 110 to 180 ml/kg/min, achieved in part because of splenic contraction and mobilization of up to 12 L
of extra red-cell-rich blood into central circulation during exercise. This innate ability to increase circulating blood volume
makes the horse a "natural blood-doper."2
Horses have some protective physiological mechanisms, says Ken McKeever, PhD, FACSM, professor of equine exercise physiology
at Rutgers University. "They can accommodate the huge amount of red cell volume that is squeezed in from the spleen at the
onset of exercise. There are also differences in the way the red cells can bend," he says. "Equine red blood cells are more
flexible and less fragile than human red blood cells, and they'll form up like a roll of coins when necessary in small vessels."
Use of rHuEPO in racing horses
The compound rHuEPO has saved many human lives and enhanced the quality of life for patients with chronic renal failure. But
as soon as it was licensed for use in human medicine, the compound was being misused by individuals in both human and equine
"We began research not only on detection methods (to try to determine its illicit use), but on whether rHuEPO would affect
aerobic capacity and athletic performance of horses," says McKeever. Some equine practitioners have questioned whether the
human form of erythropoietin would have an effect in the horse.
McKeever and his colleagues started their research with very low doses of rHuEPO (15 IU/kg given three times a week for three
weeks) in splenectomized horses to eliminate the possibility that splenic reserve was responsible for an increase in circulating
red cell volume and increased performance.
"We showed that rHuEPO causes an increase in red cell mass, hematocrit and aerobic capacity," McKeever says. "But at the same
time, we also saw an increase in blood viscosity, measured at different shear rates representative of different points in
the cardiovascular system (i.e. aorta versus capillaries). The take-home message was that the recombinant human EPO worked in horses, as suspected. But our
splenectomized study horses did not represent the intact racehorse."
McKeever, now at Rutgers Equine Science Center, did a followup study in standardbreds with intact spleens, following a similar
protocol but with a higher dose of rHuEPO (50 IU/kg given three times a week for three weeks). The purpose: to show that rHuEPO
increased red cell volume and aerobic capacity in an intact standardbred horse. But they also tried to detect antibodies to
"It was common for a certain number of horses to show a cross-reactivity problem, as if the horse was responding to a foreign
protein," McKeever says. "After three injections of rHuEPO, the horses did show evidence of antibody production."
They also showed that the erythropoietin molecules were similar in humans and horses, that the erythropoietin is excreted
fairly rapidly and that the red cells that develop stay in the system for quite a long time, as do the antibodies. (The antibody
titer can therefore be used to detect rHuEPO, requiring horses to register a specific low level before they can race.)