Effects of Intramyocardial Administration of Slow-Release Basic Fibroblast Growth Factor on Angiogenesis and Ventricular Remodeling in a Rat Infarct Model

• Published in: Circulation Journal Vol. 70; no. 4; pp. 471 - 477
• Main Authors: Shao, Zhan-Qiang, Takaji, Kentaro, Katayama, Yukihiro, Kunitomo, Ryuji, Sakaguchi, Hisashi, Lai, Zhong-Fang, Kawasuji, Michio
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 2006
• Subjects: Angiogenesis; Animals; Apoptosis; Capillaries - pathology; Delayed-Action Preparations; Echocardiography; Fibroblast Growth Factor 2 - administration & dosage; Fibroblast Growth Factor 2 - pharmacology; Fibroblast Growth Factor 2 - therapeutic use; Hydrogels; Ischemic heart disease; Male; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial remodeling; Neovascularization, Physiologic - drug effects; Rats; Rats, Sprague-Dawley; Ventricular Function; Ventricular Remodeling - drug effects
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.70.471

Background Basic fibroblast growth factor (bFGF) stimulates neoangiogenesis. Incorporation into biodegradable gelatin hydrogels provides the sustained release of bFGF. The effects of intramyocardial injections of slow-release bFGF on neoangiogenesis in a rat model of infarction were investigated. Methods and Results Myocardial infarction was induced in rats using coronary artery ligation. A total of 124 rats received an intramyocardial injection of 20 μg of bFGF, the same amount of bFGF incorporated into gelatin hydrogel (bFGF + gel), gelatin hydrogel (gel) or saline. Ventricular function was evaluated by echocardiography 2 or 4 weeks later. Morphometric and histological analyses were used to evaluate infarct size, vascular density and myocardial apoptosis. Capillary density in the infarct border zone was higher in the bFGF and bFGF + gel groups than in the saline and gel groups at 4 weeks (p<0.001). Arteriolar density was higher in the bFGF + gel group than in the other 3 groups (p<0.05). The bFGF and bFGF + gel groups contained fewer apoptotic cardiomyocytes in the border zone than the saline and gel groups (p<0.01). The bFGF+gel group had thicker (p<0.05) and less expanded infarcts (p<0.01) compared with the saline group at 4 weeks. Conclusions Incorporation of bFGF in gelatin hydrogels enhanced the effects of bFGF on arteriogenesis, ventricular remodeling and cardiac function. (Circ J 2006; 70: 471 - 477)