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Cyclooxygenase-2 plays an essential part in cardioprotection of delayed phase of recombinant human erythropoietin preconditioning in rats

Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China

Correspondence to:
Correspondence to:
Dr J Xu
Department of Anaesthesiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing, China; brightlxm{at}gmail.com

Aims: To study the cardioprotection of recombinant human erythropoietin (rhEPO) preconditioning (EPC) and to investigate the role and possible mechanism of cyclooxygenase (COX)-2 in the delayed phase of EPC.

Methods: In phase 1, myocardial ischaemia reperfusion (I-R) rat model was established by 30 minutes ligation of left descending coronary and three hours of reperfusion. Rats were given 0.9% saline solution or rhEPO 24 hours before I-R protocol. COX-2 selective inhibitor celecoxib was given for further investigation of the cardioprotection of EPC. At the end of I-R protocol, infarct sizes were measured and ultrastructural organisations were studied. In phase 2, myocardial COX-2 mRNA expressions and prostaglandins (PGs) contents were studied in different groups after euthanasia.

Results: It was found that EPC could elicit potent cardioprotection against I-R injury, shown by reduction of infarct size and improvement of ultrastructural organisation; whereas administration of celecoxib resulted in complete loss of this protection. EPC resulted in robust increase in COX-2 mRNA and PGs levels that were also abrogated by celecoxib.

Conclusions: COX-2 plays an essential part in cardioprotection of the delayed phase of EPC in rats, which might be related to actions of PGE₂ or PGI₂, or both.

Abbreviations: EPO, erythropoietin; rhEPO, recombinant human erythropoietin; EPC, erythropoietin preconditioning; COX, cyclooxygenase; PG, prostaglandin; AA, arachidonic acid; IPC, ischaemic preconditioning; RT-PCR, reverse transcription polymerase chain reaction; I-R, ischaemia reperfusion; PPC, pharmacological preconditioning

Keywords: erythropoietin; myocardial ischaemia reperfusion; cyclooxygenase-2