Role of the spleen in the exaggerated polycythemic response to hypoxia in chronic mountain sickness in rats

In a rat model of chronic mountain sickness, the excessive polycythemic res ponse to hypoxic exposure is associated with profound splenic erythropoiesi s. We studied the uptake and distribution of radioactive iron and red blood cell (RBC) morphology in intact and splenectomized rats over a 30-day hypo xic exposure. Retention of Fe-59 in the plasma was correlated with 59Fe upt ake by both spleen and marrow and the appearance of Fe-59-labeled RBCs in t he blood. 59Fe uptake in both the spleen and the marrow paralleled the prod uction of nucleated RBCs. Splenic 59Fe uptake was similar to 10% of the tot al marrow uptake under normoxic conditions but increased to 60% of the tota l marrow uptake during hypoxic exposure. Peak splenic 59Fe uptake and splen omegaly occurred at the most intense phase of erythropoiesis and coincided with the rapid appearance of Fe-59-labeled RBCs in the blood. The bone marr ow remains the most important erythropoietic organ under bath resting and s timulated states, but inordinate splenic erythropoiesis in this rat strain accounts in large measure for the excessive polycythemia during the develop ment of chronic mountain sickness in chronic hypoxia.