Abstract 1903: Erythropoietin Is More Effective Than Mechanic Postconditioning To Protect The Heart Against Ischemic-reperfusion Injury
Background: Postconditioning (PC), known as brief intermittent periods of ischemia and reperfusion immediately at the onset of reperfusion, and erythropoietin (EPO), pharmacological agent targeting endogenous mediators of PC, are known to have a cardioprotective action against ischemia-reperfusion (I/R) injury. We sought to compare the acute cardioprotective effect of EPO and PC in isolated, Langendorff-perfused rat hearts and test whether they share similar features.
Methods: Hearts were subjected to 25 min low-flow ischemia followed by 30 min of reperfusion and randomly assigned to 7 groups: Control (no intervention); PC (3 cycles of 10 sec reperfusion followed by 10 sec ischemia during the first min of reperfusion); EPO (1000 UI/kg, administered directly to isolated hearts at the last min of ischemia); PC+PI3K inhibitor wortmannin (wort, 1 μmol/L); EPO+Wort (1 μmol/L); PC+ERK1/2 inhibitor PD98059 (PD, 10 μmol/L); EPO+PD (10 μmol/L).
Results: Compared to control, hearts treated with either PC or EPO exhibited significantly improved cardiac function reflected by an increase in post-ischemic recovery of left ventricular developed pressure (LVDP) at 30 min of reperfusion (45.58±7.91 mmHg and 73.18±10.23 mmHg, respectively, vs 18.57±4.67 mmHg, p<0.05). Furthermore, EPO exhibited better LVDP than PC at 30 min of reperfusion (73.18±10.23 mmHg vs 45.58±7.91 mmHg, p<0.05). PC and EPO also significantly improved contractility (dP/dtmax) and relaxation (dP/dtmin) indices of the LV. Perfusion with wortmannin or PD98059 inhibited both EPO and PC-mediated cardioprotection. Western blot analysis at 30 min of reperfusion showed that phospho-Akt and phospho-ERK were significantly increased in both PC and EPO hearts compared to controls. Wortmannin and PD98059 significantly reduced this increased phosphorylation in the PC as well as in the EPO group.
Conclusion: Both PC and EPO afford acute cardioprotection to isolated perfused hearts subjected to I/R, requiring the PI3K and ERK1/2 pathways during reperfusion. EPO showed better protective effects than PC against reperfusion injury, leading to hopes for new therapeutic strategies in patients with acute myocardial infarction undergoing myocardial revascularization.