Physiologic studies in normal and uremic sheep. II. Changes in erythropoiesis and oxygen transport.

Red cell production and survival, cardiac output (CO), renal blood flow (RBF), serum erythropoietin (ESF), oxygen (O2) consumption, 2,3-diphosphoglycerate (2,3-DPG), P50, and circulating hemoglobin (HbC) were measured in normal sheep and in animals made chronically uremic and anemic by subtotal nephrectomy. The erythropoiesis characterizing uremic anemia was hypoproliferative as quantitated by ferrokinetics, but was still subject to normal feedback control in that erythropoiesis in normal and uremic animals increased with phlebotomy and was suppressed with transfusion. ESF levels were only measurable when the hematocrit fell below 25 in normal animals and were undetected in most stable uremics (hematocrit, 18 to 10%). HbC correlated with ESF. CO increased linearly with progressive anemia in normal and uremic states but, despite this increase, relative RBF decreased; the percent of the CO going to the kidney fell with severe anemia. Venous O2 extraction increased linearly in normal and uremic states as anemia progressed, resulting in no difference in O2 utilization between the study states. There were no correlations between 2,3-DPG, P50, or hematocrit, under any conditions. These results confirm the mechanism of anemia in chronic renal failure and demonstrate that the O2 delivery ESF erythroid marrow feedback mechanism persists in the uremic state over a wide range of hematocrits.