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.
Public Health Relevance Statement: Public Health Relevance: Percutaneous coronary intervention (PCI) to reopen blocked coronary arteries enhances myocardial salvage and outcomes, but when blood flow is re-established (reperfusion) it can lead to infarct expansion. This infarct expansion is caused in part by the "no-reflow" phenomenon that occurs in the microvasculature of the "area at risk" during reperfusion. To reduce infarct expansion during reperfusion, Endoprotech, Inc. has developed a lipid-based treatment that protects the endothelium in the microvasculature from the "no- reflow" phenomenon and enhances myocardial salvage following PCI.
NIH Spending Category: Cardiovascular; Heart Disease; Heart Disease - Coronary Heart Disease
Project Terms: Anterior; Anti-inflammatory; Anti-Inflammatory Agents; Area; Arteries; Attenuated; Autopsy; base; Blood flow; Blood Vessels; Body Weight decreased; Cardiac; Cardiopulmonary; Catheters; Cause of Death; Cell Adhesion Molecules; Cell Culture Techniques; Cell membrane; Cells; Centers for Disease Control and Prevention (U.S.); Clinical Chemistry; clinical practice; Complement; Coronary; Coronary artery; Cytoplasm; Data; Deposition; Drug Kinetics; Drug Stability; Edema; effective therapy; Endothelial Cells; endothelial dysfunction; Endothelium; Family suidae; Fibrinolysis; fluorescence imaging; Glycocalyx; Goals; Heart; Imaging Techniques; in vivo; Induced Heart Arrest; Infarction; Inflammation; Injury; instrument; Ischemia; Lead; Left; Leukocytes; Lipids; Microscopic; Modeling; Monitor; Mus; Myocardial; Myocardial dysfunction; Myocardial Infarction; Myocardial Ischemia; Myocardium; novel; novel therapeutic intervention; novel therapeutics; Organ; Outcome; Patients; percutaneous coronary intervention; Perfusion; Phase; Piloerection; Plasma; Plug-in; public health relevance; Randomized Clinical Trials; Reperfusion Injury; Reperfusion Therapy; Risk; Safety; screening; Severities; Signal Transduction; Swelling; Symptoms; systemic toxicity; Therapeutic Embolization; Toxic effect; Toxicity Tests; Troponin I; Vesicle; Warm Ischemia
