Abstract

Vasoprotective effects of erythropoietin in animal models are mediated by endothelium-derived NO and/or mobilization of EPCs (endothelial progenitor cells) and may be enhanced by ischaemia: whether they are present in humans is unknown. We examined whether the erythropoietin analogue darbepoetin improves FMD (flow-mediated dilatation), a measure of endothelium-derived NO, and whether this is influenced by preceding I/R (ischaemia/reperfusion). A total of 36 patients (50-75 years) with stable coronary artery disease were randomized to receive a single dose of darbepoetin (300 ?g) or saline placebo. FMD was measured at the brachial artery using high-resolution ultrasound. CD133?/CD34?/VEGFR2? (vascular endothelial growth factor receptor 2) circulating EPCs were enumerated by flow cytometry. Measurements were made immediately before darbepoetin/placebo and at 24 h, 72 h and 7 days. At 24 h, FMD was repeated after 20 min of I/R of the upper limb. A further group of 11 patients was studied according to the same protocol, all receiving darbepoetin, with omission of forearm I/R at 24 h. Immunoreactive erythropoietin peaked at 24 h and remained elevated at approximately 50-fold of baseline at 72 h. FMD did not differ significantly between groups at 24 h (before I/R). At 72 h (48 h after I/R), FMD was greater (by 2.3±0.5% in the darbepoetin compared with the placebo group, a 66% increase over baseline; P<0.001) and greater than FMD at the same time point without preceding I/R (P<0.01). Increases in CD133?/CD34?/VEGFR2? cells after darbepoetin did not differ according to the presence or absence of preceding I/R. Preceding I/R is required for darbepoetin to enhance endothelial function, possibly by increasing expression of the erythropoietin receptor and by a mechanism likely to involve Akt/NO rather than circulating EPCs.

Abstract

OBJECTIVE To evaluate the effects of recombinant human erythropoietin (r-HuEPO) in attempting to prevent anemia in acutely burned patients. DESIGN Prospective double-blind randomized study of 40 patients. METHODS Patients with burns from 25% to 65% total body surface were enrolled. r-HuEPO or a placebo was begun within 72 hours of admission. Cell blood count, reticulocyte counts, transfusion requirements, and blood loss were measured. Comparison was carried out by the unpaired t test. MAIN RESULTS There was no statistically significant difference in hemoglobin, hematocrit, reticulocyte count, ferritin, serum iron, total iron blinding capacity, or transfusion requirements. In patients with burns from 25% to 35%, the reticulocyte counts were statistically significantly higher. CONCLUSION In our work the administration of r-HuEPO in acutely burned patients did not prevent the development of postburn anemia or decrease transfusion requirements. Increased erythropoiesis in smaller burns (25% to 35%) was observed and may indicate a reason for further study.