191. Improvement of Myocardial Dysfunction by Therapeutic Angiogenesis Induced by Transfection of HGF Gene Using Left Ventricular Electromechanical Mapping in Porcine Chronic Myocardial Infarction Model

Abstract

Top of pageAbstract Therapeutic angiogenesis using angiogenic growth factors via direct myocardial injection has been reported to improve myocardial blood flow in several animal models and patients with ischemic heart disease. In this study, we evaluated the efficacy of therapeutic angiogenesis in porcine chronic infarction model by the direct injection of hepatocyte growth factor (HGF) into myocardium using a needle injection catheter system, to evaluate the potential utility to treat IHD patients. Ischemia was induced by placing an ameroid constrictor around the proximal left circumflex artery. Four weeks later, endocardial electromechanical mapping was used to identify the area of ischemic myocardium. The area of ischemic myocardium as evidenced by uncoupling of mechanical function and electrical activity was about 10cm2 in each group. Each pig received six injections of 0.5 ml of saline or HGF (total dose 0.4 or 4mg) to ischemic area. No animal had pericardial effusion or tamponade, and no episodes of sustained ventricular arrhythmia were noted immediately after intramyocardial injection. At 1month after injection, the ischemic area (% of pre-ischemic area) was significantly reduced in HGF (0.4 or 4mg) group as compared to control (cont;100%, HGF (0.4mg); 43%lowast, HGF (4mg); 26%**,*P<0.05,**P<0.01 vs. control).Moreover, A ratio of the ischemic territory blood supply to the normal territory evaluated by microsphere beads in each animal was significantly increased in HGF (4mg) group as compared to control (cont;0.82, HGF (0.4mg); 1.02, HGF (4mg); 1.19*,*P<0.01 vs. control). These favorable outcomes provide the potential utility to treat IHD patients using catheter-based, intramyocardial injection of HGF gene Figure 1.