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Eur J Cardiothorac Surg 2006;29:902-907
© 2006 Elsevier Science NL

Pretreatment with recombined human erythropoietin attenuates ischemia–reperfusion-induced lung injury in rats

^a Department of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, 305 Zhongshan East Road, Nanjing 210002, China
^b Department of Pathology, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing, China

Received 29 September 2005; received in revised form 14 February 2006; accepted 20 February 2006.

^_* Corresponding author. Tel.: +86 25 80860075; fax: +86 25 84819984. (Email: wu_haiwei{at}163.com).

Objective: Based on the findings that erythropoietin (EPO) has been proved to be a multiple functional cytokine to attenuate ischemia–reperfusion (I/R) injury in various organs such as brain, heart, and kidney in animals, this experiment was designed to evaluate the effect of pretreatment with recombined human erythropoietin (rhEPO) on I/R-induced lung injury. Methods: Left lungs of rats underwent 90 min of ischemia and then were reperfused for up to 2 h. Animals were randomly divided into three experimental groups as sham group, I/R group, and rhEPO + I/R group (a single dose of rhEPO was injected intraperitoneally 3000 U/kg 24 h prior to operation). Lung injury was evaluated according to semi-quantitive analysis of microscopic changes, tissue polymorphonuclear neutrophils (PMNs) accumulation (myeloperoxidase (MPO) activity), and pulmonary microvascular permeability (Evan's blue dying method). Peripheral arterial and venous blood samples were obtained for blood–gas analysis after 5 min occlusion of right lung hilus at the end of reperfusion. The serum concentration of tumor necrosis factor (TNF)- was also measured by the method of enzyme-linked immunosorbent assay. Results: Histological injury scoring revealed significantly lessened lung alveolus edema and neutrophils infiltration in the rhEPO pretreated group compared with I/R group (p < 0.05). The rhEPO pretreated animals exhibited markedly decreased lung microvascular permeability (p < 0.05) and myeloperoxidase activity (p < 0.05). Blood–gas analysis demonstrated that the pretreated animals had significantly ameliorated pulmonary oxygenation function (p < 0.05). The serum concentration of tumor necrosis factor- in rhEPO pretreated group was markedly decreased compared with that of I/R group (p < 0.05). Conclusions: Pretreatment with rhEPO appears to attenuate I/R-induced lung injury. This function is partly related with the capacity that rhEPO inhibits the accumulation of polymorphonuclear neutrophils in lung tissue and decreases the systematic expression of tumor necrosis factor-.

Key Words: Erythropoietin • Ischemia–reperfusion injury • Lung