Relative Effectiveness of Phenylhydrazine Treatment and Hemorrhage in the Production of an Erythropoietic Factor

Abstract Active plasma extract has been prepared from rabbits made anemic by phenylhydrazine treatment, but in every case where rabbits were made equally anemic by bleeding the only peripheral evidence of erythropoietic activity found after injection of plasma filtrate was the inducement of a moderate reticulocytosis in a heterologous recipient. In rabbits bled on successive days until their hematocrits were equal to paired animals made anemic by phenylhydrazine injection, there is, nevertheless, a lower oxygen carrying capacity in the phenylhydrazine injected animals. The latter have methemoglobin concenstrations amounting to approximately 24 per cent of the total blood pigment while in the bled rabbits the methemoglobin level is practically zero. Plasma extracts from phenylhydrazine treated rabbits with apparently normal or very slightly damaged livers produce factor comparable in potency to that obtained from bled animals. The most highly active preparations are obtained in phenylhydrazine treated rabbits which have severely damaged livers. The proposed hypothesis is that the factor is produced in quantity only when the effective hematocrit is below 12 to 15 per cent and when the liver is not capable of rapid active destruction of the factor or is not producing an otherwise normally occurring inhibitor. The factor obtained from phenylhydrazine treated rabbits with liver damage is markedly active as shown by significant increase in blood volume and red cell mass, an elevated red blood cell count and hematocrit, and an intense reticulocytosis.