The effect of recombinant human erythropoietin on ischemia-reperfusion injury: An experimental study in a rat TRAM flap model

Background: Erythropoietin is traditionally known to regulate erythropoiesis, but recently its protective effect against ischemia-reperfusion injury has been studied in cardiovascular and neuronal systems. This study investigated the effect of recombinant human erythropoietin on ischemia-reperfusion injury in a rat transverse rectus abdominis musculocutarreous (TRAM) flap model. Methods: Twenty-four Sprague-Dawley rats were divided into a control group (n = 12) and a group treated with erythropoietin (n = 12). A superiorly based TRAM flap was elevated and ischemic insult was given for 4 hours. Thirty minutes before reperfusion, single-dose recombinant human erythropoietin (5000 IU/kg) was injected through the intraperitoneal route in the treatment group. At 24 hours postoperatively, systemic neutrophil count, tissue myeloperoxidase activity, amount of malondialdehyde, nitric oxide content, tissue water content, and histologic finding of inflammation were evaluated. At day 10 postoperatively, flap survival rate, angiogenesis, and change in hematocrit level were evaluated. Results: The myeloperoxidase activity and tissue water content were significantly lower (p < 0.01 and p < 0.005, respectively), and the tissue nitric oxide level was significantly higher (p < 0.005) in the treatment group 24 hours after reperfusion. Perivascular neutrophil infiltration and intravascular adhesion were marked in the control group. Mean flap survival after 10 days was 69 percent in the treatment group and 47 percent in the control group, demonstrating a significant difference (p < 0.005). Neovascularization in the treatment group was also greater than that in the control group. No significant hematocrit rise was noted 10 days after erythropoietin administration. Conclusion: Recombinant human erythropoietin improved flap survival in ischemia-reperfusion-injured rat TRAM flaps by the possible mechanism of suppressed inflammation, decreased infiltration of neutrophils, increased nitric oxide, and enhanced angiogenesis.