Effects of erythropoietin on systemic hematocrit and oxygen transport in the splenectomized horse

To test the hypotheses that erythropoietin (rhuEPO) treatment increases systemic hematocrit, maximal O2 uptake (VO2max, by elevated perfusive and diffusive O2 conductances) and performance five female horses (4-13 years) received 15 IU/kg rhuEPO (erythropoietin) three times per week for three weeks. These horses had been splenectomized over 1 year previously to avoid confounding effects from the mobilization of splenic red blood cell reserves. Each horse performed three maximal exercise tests (one per month) on an inclined (4°) treadmill to the limit of tolerance; two control trials and one following EPO treatment. Measurements of hemoglobin concentration ([Hb] and hematocrit), plasma and blood volume, VO2, cardiac output as well as arterial and mixed venous blood gases were made at rest and during maximal exercise. EPO increased resting [Hb] by 18% from 13.3 ± 0.6 to 15.7 ± 0.8 g/dL (mean ± SD) corresponding to an increased hematocrit from 36 ± 2 to 46 ± 2% concurrent with 23 and 10% reductions in plasma and blood volume, respectively (all P<0.05). EPO elevated VO2max by 20% from 25.7 ± 1.7 to 30.9 ± 3.4 L/min (P<0.05) via a 17% increase in arterial O2 content and 18% greater arteriovenous O2 difference in the face of an unchanged cardiac output. To achieve the greater VO2max after EPO, diffusive O2 conductance increased ∼ 30% (from 580 ± 76 to 752 ± 166 mL O2/mmHg/min, P<0.05) which was substantially greater than the elevation of perfusive O2 conductance. These effects of EPO were associated with an increased exercise performance (total running time: control, 216 ± 72; EPO, 264 ± 48 s, P<0.05). We conclude that EPO substantially increases VO2max and performance in the splenectomized horse via improved perfusive and diffusive O2 transport.