There is a need to develop alternative treatment strategies for the 30% of patients with critical leg ischemia (CLI) for whom conventional modes of revascularization fail. The efficacy erythropoietin (EPO) in this regard has been verified in preclinical models. Erythropoietin receptors are expressed in the human skeletal muscle and possibly, upregulated in CLI. Furthermore, EPO induces angiogenesis and prevents apoptosis in the ischemic skeletal muscle. The use of EPO in conjunction with autologous bone marrow cells or gene-induced angiogenesis with vascular endothelial growth factor may be more effective in inducing angiogenesis and protecting the critically ischemic leg than EPO alone. The recently synthesized nonhemopoietic derivatives of EPO (eg, asialo erythropoietin and carbamylated erythropoietin) allow higher doses to be administered to achieve tissue protective effects, without an unwanted increase in hematocrit. This may allow translation of preclinical studies into clinical trials.
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