J004 Darbepoetin-<alpha> protects heart against ischemia-reperfusion: role of BCL-2 family proteins

Heart can usually survive a short period of ischemia, but when this period is too long, damages of the cardiac tissue became irreversible and are possibly exacerbated by blood reperfusion. Loss of cardiac myocytes via apoptosis is believed to contribute to the continuous decline of ventricular function described in heart failure. Limiting theses deleterious responses is of major importance in cardiac surgery and for the treatment of coronary thrombosis. The purpose of this study was to assess the short and long term cardioprotective effects of the long lasting effect erythropoietin analogue darbepoetin-α (DA) in a myocardial ischemia-reperfusion model in rat and ; to investigate the signaling pathway through which DA potentially limits apoptosis of cardiomyocytes.Rat were subjected to 40 min left coronary artery ligation followed by 3h, 72h or 4 weeks reperfusion and they received either DA (3 or 30 μg/kg) or vehicle i.v. prior ischemia. Left ventricle (LV) function was assessed by echocardiography prior surgery and after reperfusion. Hearts were collected for histological analysis, protein analysis and reactive oxygen species (ROS) production.In DA3 and DA30 72hrs groups, both LV shortening fraction and LV ejection fraction were higher vs. control (P