Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The effect of erythropoietin (EPO) on neonatal hearts is not well understood. The current hypothesis is that EPO has protective effects against ischaemia-reperfusion when administered prior to ischaemia induction. Systolic and diastolic indices, as well as the Akt and extracellular-regulated kinase (Erk) signalling pathways, were studied in vivo using a neonatal pig heart model. Regional ischaemia was induced for 45 min by the ligation of the left anterior descending artery, followed by 90 min of reperfusion. The treatment groups consisted of: (i) untreated controls, (ii) treatment with EPO 3 min prior to ischaemia and (iii) treatment with EPO 24 h before ischaemia. Sophisticated myocardial contractility indices were assessed by pressure/volume loops of the left ventricle. The Akt and Erk pathways were evaluated via a western blot. Elastance was found to be higher in the group receiving EPO 3 min prior to ischaemia. In addition, preload recruitable stroke work was higher for both groups receiving EPO prior to ischaemia when compared with controls. The time constant of the isovolumic relaxation and end-diastolic pressure-volume relationship did not differ between the three groups after 90 min of reperfusion. Furthermore, EPO treatment enhanced phosphorylation of Akt, but not Erk, and EPO-treated animals showed lower levels of apoptosis-related proteins. EPO had a protective effect on neonatal systolic function after ischaemia/reperfusion injury, but no effect on diastolic function. This cardioprotective effect might be mediated by the activation of the Akt pathway.431156162Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2009/09583-3]