Erythropoietin (EPO) and ischemic postconditioning (IPost) have been shown to attenuate myocardial reperfusion injury. Aims: This study compared the mechanisms of the acute cardioprotective effect of EPO and IPost and tested whether they share similar signalling pathways in isolated rat hearts, focussing on phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2 pathways.

Hearts were subjected to 25 min global ischemia followed by 30 min of reperfusion. 7 groups were tested: control (no intervention); IPost (3 cycles of 10 sec reperfusion/10 sec ischemia at the onset of reperfusion); EPO (1000 UI/kg, at the onset of reperfusion); IPost+PI3K inhibitor wortmannin (Wort, 1 μmol/L); EPO+Wort; IPost+ERK1/2 inhibitor PD98059 (PD, 10 μmol/L); EPO+PD.

IPost- or EPO-treated hearts exhibited significantly improved left ventricular function reflected by an increase in postischemic recovery of left ventricular developed pressure (LVDP) and improved contractility (dP/dtmax) and relaxation (dP/dtmin) indexes throughout the reperfusion period compared with control hearts. EPO showed better LVDP than IPost at 30min reperfusion (73.18±10.23 mmHg vs. 48.11±7.92 mmHg, ρ<0.05). Wort or PD fully prevented both EPO and IPost-mediated cardioprotection. Phosphorylation of myocardial Akt was significantly increased in both IPost and EPO groups. However, phosphorylation levels of ERK1/2 and the downstream target GSK-3β were significantly increased in EPO group only.

EPO and IPost share similar intracellular cardioprotective pathways. EPO exhibits better cardioprotective effects than IPost against reperfusion injury leading to great hopes in EPO as a pharmacological agent of postconditioning. This increased resistance to myocardial ischemia induced by EPO seems to be mediated by an enhanced phosphorylation of ERK1/2.