1203-P: High-Dose Erythropoietin and Cardiac Function in Mice

Abstract

Erythropoietin (EPO) is the cytokine required for erythropoiesis. EPO stimulated increase in hematocrit elevates blood viscosity that may cause hemodynamic risks in the cardiovascular system, promote ischemic heart disease, and stroke. Herein, we studied the physiological effect of high dose exogenous EPO (i.p. 3000 U/kg, 3 times/week for three weeks) with high fat diet (HFD) on cardiac function using echocardiographic measurements in young wild-type (WT) male and female mice and older obese WT male mice with fat mass >45%. In young male mice, but not in female and older obese male mice, EPO treatment with HFD decreased body weight and fat mass accumulation compared with saline, although all groups showed similar EPO stimulated increases in hematocrit. EPO reduced ejection fraction and fractional shortening of left ventricle (LV) in both young male and female mice. This is consistent with the previous report that mice with chronic overexpression of human EPO have decreased fractional shortening of LV. In contrast, older obese male mice have reduced basal ejection fraction and fractional shortening that remain unchanged with EPO treatment indicating that the changes in basal ejection fraction and fractional shortening with EPO treatment in younger mice were not due to EPO stimulated increase in red cell mass. EPO decreased peak velocity of blood flow in the pulmonary artery in all groups indicative of increased hematocrit promoting higher blood viscosity. In addition, EPO increased LV posterior wall thickness in diastole in older male obese mice. This is consonant with observations that high hematocrit is related to concentric left ventricular hypertrophy in human. These data suggest that high dose EPO treatment may be associated with possible cardiac dysfunction with decreased ejection fraction and fractional shortening of LV, and alteration of left ventricular geometry. Disclosure J. Lee: None. C. T. Noguchi: None.