The mechanism by which plethora suppresses erythropoiesis.

E RYTHROPOIETIN is believed to be the prime physiologic regulator of erythropoiesis.1 It is generally assumed that erythropoietin production is chiefly controlled by the demands of tissues for oxygen relative to their oxygen supply.1 According to this hypothesis transfusion-induced polycythemia results in suppression of erythropoietin production ( and consequently of erythropoiesis ) by virtue of its ability to increase the oxygen supply to tissue.2 However, transfusion-induced polycythemia of a marked degree is associated with an increase in viscosity which might actually diminish oxygen supply to the tissues.3 A compensatory increase in cardiac output or fall in peripheral resistance could overcome this rheological disadvantage of higher blood viscosity following hypertransfusion.4’5 Recently, however, it has been suggested that marked post-transfusion polycythemia results in an inhibition of erythropoietin production by a mechanism which is independent of the increased oxygen content of blood.6’7 The present study was designed to demonstrate in mice the effect of an increase in hematocrit on erythropoietin production without a concomitant augmentation of the oxygen content of blood. This purpose was accomplished either by dehydrating mice or by transfusing them with methemoglobinized cells from a patient with hereditary methemoglobinemia due to deficiency of NADH-methemoglobin reductase ( diaphorase ) #{149}8 Such cells were chosen because methemoglobin of normal nitrite-treated human or mouse red cells was shown to be completely reduced within one to hvo hours after transfusion. The same was experienced with cyanmethemoglobincontaining cells.