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CARDIOVASCULAR ANESTHESIOLOGY

Lipopolysaccharide Evokes Resistance to Erythropoiesis Induced by the Long-Acting Erythropoietin Analogue Darbepoetin Alfa in Rats

Peter Brendt, MD^*, Ariane Horwat^*, Simon T. Schäfer, MD^*, Sven C. Dreyer, MD^*, Joachim Göthert, MD, and Jürgen Peters, MD^*

From the *Klinik für Anästhesiologie und Intensivmedizin; Universität Duisburg-Essen; and Klinik für Hämatologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.

Address correspondence to Dr. Peter Brendt, Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Hufelandstr. 55, Essen D-45122, Germany. Address e-mail to Peter.Brendt{at}uni-duisburg-essen.de.

Abstract

BACKGROUND: Anemia is common in patients with sepsis but its mechanism is unknown. We tested the hypothesis that effects on erythropoiesis evoked by darbepoetin alfa (DA), a long-acting erythropoietin analog, are diminished by lipopolysaccharide (LPS).

METHODS: We performed a prospective, controlled, randomized animal study (male Lewis rats n = 44). The interventions we used were intraperitoneal injection of Escherichia coli LPS (10 mg/kg) or vehicle followed by either DA (25 µg/kg) or vehicle (four experimental groups). Blood and reticulocyte counts and variables of iron metabolism were measured at baseline and 3 and 14 days after interventions.

RESULTS: Animals treated with DA alone showed an eightfold increase in reticulocyte count from baseline on Day 3, whereas no increase was seen in animals administered LPS or LPS/DA. On Day 14, the red blood cell count and hemoglobin concentration had increased by approximately 10% from baseline (P < 0.001) in the DA group but had decreased after LPS on Days 3 and 14 (P < 0.05) and in animals administered LPS/DA. Consumption of iron was seen on Day 3 in the DA group but not after LPS or LPS/DA combined. Values of ferritin and transferrin did not change between groups.

CONCLUSION: LPS abolishes erythropoiesis and iron use evoked by DA and this is accompanied by a decrease in hemoglobin concentration and red blood cell concentration. Accordingly, endotoxin suppresses DAs ability to increase erythropoiesis.