EXCESSIVE ERYTHROCYTOSIS IN TRANSGENIC MICE OVEREXPRESSING ERYTHROPOIETIN IS ACCOMPANIED BY A MODERATELY INCREASED WHOLE BLOOD VISCOSITY DUE TO AN INCREASED ERYTHROCYTE FLEXIBILITY

Johannes Vogel.
Institute of Veterinary Physiology, University of Zürich, Zürich, Switzerland.

Severe elevation of red blood cell number is often associated with hypertension and thromboembolism resulting in severe cardiovascular complications. Even without specific complications such as thromboembolism, the elevation of whole blood viscosity (WBV) as a consequence of increased red cell mass strains the heart which might finally result in cardiovascular decompensation. We analyzed adaptive mechanisms to excessive erythrocytosis in our transgenic (tg) mice that due to hypoxiaindependent erythropoietin (Epo) overexpression reached hematocrit values around 0.85 without alteration of blood pressure, heart rate or cardiac output. To this end plasma viscosity as well as WBV were measured using a rotation viscosimeter. Plasma protein concentration and pattern were also determined. In addition, reticulocyte counts, mean corpuscular volume (MCV) and mean corpuscular hemoglobine concentration (MCHC) were determined since these parameters influence the red cell flexibility. Furthermore the axial elongation of the erythrocytes was measured at physiological shear rates using ektacytometry. Tg mice showed doubled reticulocyte counts and an about 30% higher MCV. MCHC was slightly but not significantly lower in tg mice. No differences could be found concerning the plasma protein concentration or pattern between both mouse lines. While plasma viscosity did not differ between tg and wt, tg WBV increased to a lower degree (4-fold) than expected from corresponding hemoconcentrated wt blood (8-fold). This moderate increase in WBV is explicable by the up to 3-fold higher elongation of tg erythrocytes at physiological shear rates. Apart from the nitric oxide mediated vasodilation we reported earlier, adaptation to excessive erythrocytosis in tg mice involves regulated elevation of whole blood viscosity by increasing erythrocyte flexibility.