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The Effect of Erythropoietin on Ischemia-Reperfusion Injury: An Experimental Study in Rat TRAM Flap Model  

Kim, Eun Key (Department of Plastic Surgery, Asan Medical Center, University of Ulsan College of Medicine)
Hong, Joon Pio (Department of Plastic Surgery, Asan Medical Center, University of Ulsan College of Medicine)
Publication Information
Archives of Plastic Surgery / v.33, no.5, 2006 , pp. 621-626 More about this Journal
Abstract
Purpose: Erythropoietin is traditionally known to regulate erythropoiesis, but recently its protective effect against ischemia-reperfusion injury has been studied mainly in cardiovascular and neuronal systems. This study was planned to investigate the effects of recombinant human erythropoietin on ischemia-reperfusion injury in rat TRAM flap model. Methods: Superiorly based TRAM flap was elevated and ischemic insult was given for four hours. Thirty minutes before reperfusion, single dose recombinant human Erythropoietin(5000IU/kg) was injected via intraperitoneal route in the treatment group. At 24 hours postoperatively, systemic neutrophil count, tissue myeloperoxidase activity, malonyldialdehyde amount, nitric oxide content, tissue water content and histologic finding of inflammation was evaluated. On 10 days postoperatively, flap survival rate, angiogenesis and change in hematocrit level was evaluated. Results: Tissue nitric oxide level was significantly higher and myeloperoxidase activity was significantly lower in the treatment group 24 hours after reperfusion. Tissue water content was significantly lower in the treatment group. Perivascular neutrophil infiltration and intravascular adhesion was marked in the control group. Mean flap survival after ten days was 69% in the treatment group, and 47% in the control group, demonstrating a significant difference. Neovascularization in the treatment group also outnumbered the control group. No significant hematocrit rise was noted ten days after erythropoietin administration. Conclusion: Recombinant human Erythropoietin improved flap survival in ischemia-reperfusion injured rat TRAM flaps, at least partially owing to suppressed inflammation, increased nitric oxide, and enhanced angiogenesis.
Keywords
Erythropoietin; Ischemia-reperfusion; Flap survival; Angiogenesis;
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1 Patel NS, Sharples EJ, Cuzzocrea S, Chatterjee PK Britti D, Yaqoob MM, Thiemermann C: Pretreatment with EPO reduces the injury and dysfunction caused by ischemia/reperfusion in the mouse kidney in vivo. Kidney Int 66: 983, 2004   DOI   ScienceOn
2 Haroon ZA, Amin K Jiang X, Arcasoy MO: A novel role for erythropoietin during fibrin-induced wound-healing response. Am J Pathol 163: 993, 2003   DOI   ScienceOn
3 Rafiee P, Shi Y, Su J, Pritchard KA Jr, Tweddell JS, Baker JE: Erythropoietin protects the infant heart against ischemia-reperfusion injury by triggering multiple signaling pathways. Basic Res Cardiol 100: 187, 2005   DOI   ScienceOn
4 Buemi M, Galeano M, Sturiale A, Ientile R, Crisafulli C Parisi A, Catania M, Calapai G, Impala P, Aloisi C Squadrito F, Altavilla D, Bitto A, Tuccari G, Frisina N: Recombinant human erythropoietin stimulates angiogenesis and healing of ischemic skin wounds. Shock 22: 169, 2004   DOI   ScienceOn
5 Shi Y, Rafiee P, Su J, Pritchard KA Jr, Tweddell JS, Baker JE: Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels. Basic Res Cardiol 99: 173, 2004   DOI   ScienceOn
6 Parsa CJ, Kim J, Riel RU, Pascal LS, Thompson RB, Petrofski JA, Matsumoto A, Stamler JS, Koch WJ: Cardiaprotective effects of erythropoietin in the reperfused ischemic heart: a potential role for cardiac fibroblasts. J Bioi Chem 279: 20655, 2004   DOI   ScienceOn
7 Bradford MM: A rapid and sensitive for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248, 1976   DOI   ScienceOn
8 Moon C Krawczyk M, Ahn D, Ahmet I, Paik D, Lakatta EG, Talan MI: Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci USA 100: 11612, 2003
9 Squadrito F, Altavilla D, Squadrito G, Campo GM, Arlotta M, Quartarone C Saitta A, Caputi AP: Recombinant human erythropoietin inhibits iNOS activity and reverts vascular dysfunction in splanchnic artery occlusion shock. Br J Pharmacol 127: 482, 1999
10 Santhanam AV, Smith LA, Akiyama M, Rosales AG, Bailey KR, Katusic ZS: Role of endothelial NO synthase phosphorylation in cerebrovascular protective effect of recombinant erythropoietin during subarachnoid hemorrhage-induced cerebral vasospasm. Stroke 36: 2731, 2005   DOI   ScienceOn
11 Saray A, Ozakpinar R, Koc C Serel S, Sen Z, Can Z: Effect of chronic and short-term erythropoietin treatment on random flap survival in rats: an experimental study. Laryngoscope 113: 85, 2003   DOI   ScienceOn
12 Galeano M, Altavilla D, Cucinotta D, Russo GT, Calo M, Bitto A, Marini H, Marini R, Adamo EB, Seminara P, Minutoli L, Torre V, Squadrito F: Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse. Diabetes 53: 2509, 2004   DOI   ScienceOn
13 Bor-Kucukatay M, Yalcin O, Meiselman HJ, Baskurt OK: Erythropoietin-induced rheological changes of rat erythrocytes. Br J Haemaiol 110: 82, 2000   DOI   ScienceOn
14 Bogoyevitch MA: An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res 63: 208, 2004   DOI   ScienceOn
15 Jaquet K Krause K Tawakol-Khodai M, Geidel S, Kuck KH: Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res 64: 326, 2002   DOI   ScienceOn