Protecting the damaged heart from excessive cell death represents a novel therapeutic strategy that may lead to increased viable myocardial after ischemic insults such as myocardial infarction (MI). The hematopoietic cytokine erythropoietin (EPO) has recently shown to offer in vivo neuroprotection following hypoxia/ischemia stress. This appears to involve inhibition of programmed cell death or apoptosis. This proposal is formulated to test whether EPO has any cellular protection effects in the heart following hypoxia/ischemia such as after an MI. The Central Hypothesis of this proposal is that EPO can protect myocytes against cell death in the ischemic heart. Moreover, increasing viable myocardium post-MI with EPO treatment will lead to improved cardiac function acutely and chronically. To test this hypothesis, we will utilize in vitro and in vivo model assays including cultured adult ventricular cardiomyocytes and an ischemia model in the rabbit where we will analyze EPO's effect on apoptosis and cardiac function acutely and chronically post-MI.
