The Erythropoietic Effect of Urine and Plasma of Repeatedly Bled Rabbits

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Abstract
1. The reticulocyte response of rabbits bled in a standard manner is significantly greater after the injection of anemic rabbit plasma, than after the injection of normal rabbit plasma. The effect of anemic rabbit plasma disappears after the exposure to 100 per cent oxygen, but not after exposure to air. The activity of anemic rabbit plasma is not due to the presence of high concentrations of vitamin B12 or folic acid. 2. The recovery of hemoglobin concentration after a standard hemorrhage is described by a first order exponential equation. The speed of recovery is characterized by the time constant of regeneration. The velocity of hemoglobin regeneration, after a standard hemorrhage in rabbits injected with plasma of anemic animals, is greater than that of controls injected with normal rabbit plasma. Anemic rabbit plasma loses its erythropoietic effect after boiling at pH 5.5 for 15 minutes. 3. The repeated injection of anemic rabbit plasma in normal rabbits produces a significant rise of reticulocytes, erythrocytes, and hemoglobin concentration. 4. The injection of urine of anemic animals increases the speed of hemoglobin regeneration after a standard hemorrhage in rabbits. The activity of the urine of anemic rabbits is lost by boiling at pH 9.0 for 5 minutes, but not after the same treatment at pH 5.5. Urine of anemic animals loses its erythropoietic action after 16 hours dialysis. 5. It is concluded that the plasma and urine of animal with increased erythropoiesis contains a factor or factors (erythropoietins) which are probably the humoral mediators of the primary erythropoietic stimulus.