Erythropoietin improves cardiac contractility in post-hypoxic mice

Abstract

Mice myocardia, in which plasma erythropoietin (EPO) concentrations were modified in response to different experimental conditions, were studied to evaluate contractility (dF/dt). CF1 mice were randomly separated into four main groups: group I, normocythaemic normoxic: group II-a. normocythaemic intermittently exposed to hypobaria for 72 h: group II-b. normocythaemic intermittently exposed to hypobaria for 3 weeks: group III. hypertransfused polycythaemic exposed to 72 h hypobaria; and group IV, hypertransfused polycythaemic maintained in normobaric air. Plasma EPO, contractile studies and binding assays were performed. The dF/dt was significantly higher in group II-a than in group I and group II-b: but in groups III and IV, the dF/dt was reduced. The toxic action of ouabain was reduced and delayed in its onset, accompanied by increased numbers of 3H-ouabain binding sites in group II-a. Contractility was positively correlated with plasma EPO (pEPO) in the different groups. Treating group I with recombinant human (rHu)-EPO enhanced contractility while treating group II-a with a monoclonal anti-EPO decreased the dF/dt. The inhibition of enzymatic pathway(s) known to participate in the cytokines signal transduction. decreased the basal dF/dt values on atria from group II-a and on group I atria treated with rHu-EPO. The results demonstrated: (1) a cardiac non-haematopoietic effect of EPO; (2) that mice in which the pEPO concentration increased showed improvement in contractility and in the therapeutic action of ouabain; and (3) it is possible that EPO may act as a cardioprotective agent by modulating the cardiac Na+-K+ pump.