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

•Erythropoietin treatment increases arterial hematocrit and [hemoglobin] concomitant with reduced plasma volume in splenectomized horses.•During maximal exercise, cardiac output is unchanged and V˙O2max (and exercise performance) is enhanced 19%.•The increase in V˙O2max is due to augmented perfusive (increased 20%) and diffusive (increased 30%) O2 transport.•The latter suggesting that the increased systemic hematocrit raises capillary [hemoglobin] and facilitates blood-myocyte O2 flux.

To test the hypotheses that erythropoietin (rhuEPO) treatment increases systemic hematocrit, maximal O2 uptake (V˙O2max, 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, V˙O2, 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 V˙O2max 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 V˙O2max 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 V˙O2max and performance in the splenectomized horse via improved perfusive and diffusive O2 transport.