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 musculocutaneous (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.


CONCLUSIONS
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.
Kim
Eun Key
EK
Seoul, Korea From the Department of Plastic and Reconstructive Surgery, University of Ulsan College of Medicine, Asan Medical Center.
Hong
Joon Pio
JP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D006400:Hematocrit; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D008315:Malondialdehyde / Q000032:analysis; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D017568:Rectus Abdominis / Q000098:blood supply* / Q000601:surgery; D015427:Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D013524:Surgical Flaps / Q000098:blood supply*
D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide; D008315:Malondialdehyde; D009195:Peroxidase