According to the CDC in 2013, ischemic heart disease is the leading cause of death worldwide, and in the US approximately 450,000 patients died of ischemic heart disease. It is well established in clinical practice that recanalization of he infarct related artery (IRA) using percutaneous coronary intervention (PCI) enhances myocardial salvage and outcomes in patients with ST-segment elevation myocardial infarction (STEMI). When the duration of ischemia exceeds 1 h from onset of symptoms, reperfusion injury following PCI often leads to infarct expansion due to the no-reflow phenomenon in the microvasculature of the area at risk. Multiple mechanisms are thought to contribute to no-reflow, and no effective treatment to ameliorate no-reflow and infarct expansion during reperfusion has been identified in large randomized clinical trials following STEMI and PCI. EndoProtech, Inc. has developed a novel therapeutic approach that alters the lipid content of endothelial cells (ECs) during PCI, which has a stabilizing effect on the microvascular endothelium and ameliorates no-reflow in the area at risk during reperfusion. The overall goal of this project is to demonstrate the safety and efficacy of our lipotherapy in enhancing myocardial salvage following STEMI and PCI. The aims of this Phase I proposal are: 1) Evaluate lipotherapy safety with preliminary screening tests for toxicity, and 2) Evaluate lipotherapy efficacy in a swine infarct model. Successful completion of these aims will demonstrate that administration of our lipotherapy to the IRA during PCI just prior to reperfusion is safe, reduces no-reflow in the are at risk and enhances myocardial salvage. During Phase II, aims will be consistent with studies required by the FDA to ultimately provide the necessary data that will support a new drug application.