Scientific Heading: RED CELLS Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity

摘要: Severe elevation of red blood cell number is often associated with hypertension and thromboembolism resulting in severe cardiovascular complications. However, some individuals such as high altitude dwellers cope well an increased hematocrit. We analyzed adaptive mechanisms to excessive erythrocytosis our transgenic (tg) mice that due hypoxia-independent erythropoietin (Epo) overexpression reached hematocrit values 0.8 0.9 without alteration pressure, heart rate or cardiac output. Extramedullar erythropoiesis occurred the tg spleen leading splenomegaly. Upon splenectomy, decreased from 0.89 0.62. Tg showed doubled reticulocyte counts mean corpuscular volume. In plasma volume was not elevated whereas 25% body weight compared 8% wildtype (wt) siblings. While viscosity did differ between wt, whole-blood a lower degree (4-fold) than expected corresponding hemoconcentrated wt (8-fold). This moderate increase explicable by up 3-fold higher elongation erythrocytes at physiological shear rates. Apart nitric oxide mediated vasodilation we reported earlier, adaptation involves regulated increasing erythrocyte flexibility. KEYWORD polycythemia, extramedullary erythropoiesis, splenomegaly, microcirculation For personal use only. guest on June 3, 2013. bloodjournal.hematologylibrary.org From