Abstract

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.