Abstract 12538: A Novel Method to Therapeutic Angiogenesis by Sustained Release of Basic Fibroblast Growth Factor Using Biodegradable Gelatin Hydrogel Sheet in a Canine Chronic Myocardial Infarction Model

Background: As therapeutic angiogenesis, we have ever used basic fibroblast growth factor (bFGF) with gelatin hydrogel (GH) for covering problems of gene therapy and shown the efficacy in several animal and clinical studies. This study investigated the safety and efficacy of a sustained release of bFGF with biodegradable GH sheet in canine chronic myocardial infarction (MI) models. Methods: First, we evaluated the safety in accordance with standards of Good Laboratory Practice in 9 dogs. Saline or bFGF with GH sheets were covered the left ventricular wall and we evaluated the heats and other organs by immunohistochemical studies after 4 weeks in three groups: saline group (n=3), low-dose group (40μg bFGF, n=3), high-dose group (200μg bFGF, n=3). Secondly, we evaluated the efficacy in 12 dogs. Canine chronic MI models were induced by ligation of the left anterior descending coronary artery and its diagonal branches. At 4 weeks later, saline or bFGF with GH sheets were covered the ischemic area of left ventricular wall: control group (saline, n=5) and bFGF group (200μg bFGF, n=7). At 6 weeks after treatment, we evaluated the efficacy by immunohistochemical and echocardiographic studies. Results: Regarding the safety, the blood levels of bFGF were not detected in all groups and histological abnormalities of heart or other organs were not shown in all groups at 4 weeks. Concerning the efficacy, bFGF with GH sheet improved fractional shortening significantly (18.8% ± 1.9% and 11.9% ± 1.4% in the bFGF and control groups, respectively, p Conclusions: Therapeutic angiogenesis by bFGF using biodegradable GH sheet was safe, increased the capillary density, and improved left ventricular function in canine chronic MI models, so it may be a capable strategy for treating chronic MI patients.