) Chronic heart failure (HF) is a major public health problem. There are 5 million patients with HF in US & 400,000 cases are added each year. Myocardial infraction (MI) is the most common cause of HF. The events that mediate the progression to HF following a MI are not well understood but inadequate infarct segment perfusion (due to a closed infarct related artery) is one strong predictor for HF following an MI. An open artery has been shown to improve prognosis following an MI, even when reperfusion is obtained late after an infarct, beyond the usual window for myocardial salvage. The methods to achieve this have been invasive, with some morbidity. Growth factors, lie Vascular Endothelial Growth Factor (VEGF) can induce neoangiogenesis and could theoretically mediate the pharmacological equivalent of an """"""""open infarct related artery"""""""". This strategy if successful, could obtain some of the benefits seen with a catheter induced open artery, but with much less morbidity. This hypothesis has never been evaluated. We hypothesized that administering VEGF into the infarcted heart will result in peri-infarct neovascularisaton which, like an open infarct related artery, will improve cell metabolism & tissue viability, Anti-apoptotic effects of VEGF will additionally contribute to better viability. Al of these actions will reduce ventricular and cellular remodeling & improve ventricular function. Myocardial infarction will be created in pegs using well standardized protocols (coronary artery ligation). VEGF 165 will be continuously infused into the peri-infarct area, for 4 weeks (using a mini pump). A group of similar animals getting saline will act as controls. Pigs will then undergo a hemodynamic study with an Impedance Catheter (for pressures and pressure- volume loops), an echocardiogram (to measure function & ventricular remodeling), a Sestamibi scan to estimate """"""""area of risk"""""""" and microsphere injections to estimate regional blood flow. On day #3, Sestamibi scans will be repeated, a PET scan will be done to measure coronary flow (using 15O-Water at rest & post adenosine) and myocardial glucose uptake (using FDG for viability studies). Animals will be followed for 4 weeks, when all of the tests will be repeated once again. In addition they will have a MRI study with MR """"""""Tagging"""""""" to measure regional flow, & function. Following this, they will be sacrificed and their tissues (Scar, peri-MI area and remote area) will be analyzed for (a) infarct sizing, (b) degree of neovascularisation & VEGF expression (using immunocytochemistry), and (c) degree of apoptosis. Finally, cardiomyocytes will be isolated from the peri-infarct and remote regions and studied for remodeling.
