351. Gene Electrotransfer of pVEGF in a Porcine Model to Induce Angiogenesis and Improve Cardiac Function

Abstract

Nonviral gene therapy is an attractive method for treating cardiovascular disease; however, achieving appropriate gene expression levels is often problematic. Gene electro transfer (GET) can be safely used to enhance expression. We have previously reported on establishing GET protocols to safely and effectively delivering plasmids encoding luciferase, green fluorescent protein or VEGFA directly to the heart in a porcine model. In the current study, we tested whether gene delivery of VEGF via GET could induce angiogenesis and improve cardiac function in a porcine ischemic model. Domestic farm pigs were anesthetized and intubated followed by median sternotomy to expose the heart. The left anterior descending coronary artery was partially tied off to induce localized ischemia. Animals received no treatment, injection of pVEGF or injection of pVEGF with electro transfer. Treatment was performed at four sites surrounding the ischemic region on the border of viable and ischemic myocardium. A SPY Intraoperative Perfusion Assessment System was utilized to determine the area of ischemia and quantify the approximate reduction in perfusion and to identify the area of ischemia before treatment. The animals were followed for seven weeks. Ultrasound evaluation and arteriograms were performed prior to surgery, post treatment, 2 weeks post treatment and 7 weeks post treatment. Arteriograms suggest the growth of blood vessels as early as 2 weeks. Spy analysis revealed significant increase in perfusion within the ischemic zone in animals treated with pVEGF +GET compared to controls. Echography showed improved cardiac output was significantly greater (p<0.03) 14 days post-infarct in GET treated animals compared to values immediately after surgery. Based on these results, gene delivery to the heart can be successfully accomplished using in vivo GET and evidence suggests the potential for a therapeutic effect.