Intramyocardial sustained delivery of basic fibroblast growth factor improves angiogenesis and ventricular function in a rat infarct model

Abstract

Recently we have demonstrated that the release of basic fibroblast growth factor (bFGF) from a biodegradable gelatin hydrogel carrier depends on the degradation of hydrogel in vivo. The purpose of our study was to assess whether bFGF-incorporating gelatin hydrogels induce myocardial angiogenesis and improve left ventricular function in the infarcted myocardium of rats. Studies were conducted in 22 Lewis rats after a 4-week ligation of the proximal left anterior descending coronary artery. The rats were randomized into the following two groups: the control group (n = 11) had an intramyocardial injection of saline alone, and the FGF group (n = 11) had gelatin hydrogel microspheres containing 100 μg of bFGF injected into the border zone of the infarct area after the repeat left thoracotomy. For visualization of the regional myocardial blood flow in the rat heart, ²⁰¹Tl images were taken just before and 4 weeks after the treatment using a 4-head single photon emission computed tomography scanner with pinhole collimators. Left ventricular function was also assessed with echocardiography and a micromanometer-tipped catheter. Finally, the extent of myocardial angiogenesis was evaluated quantitatively in the postmortem analysis. The ²⁰¹Tl defect score in the control group remained unchanged before and after the treatment, whereas it decreased significantly in the FGF group. Both regional and global left ventricular function was significantly better in the FGF group compared with the control group. The vascular density in the border zone of the infarct in the FGF group was significantly higher than that in the control group. In conclusion, intramyocardial injection of bFGF-impregnated gelatin hydrogels induces functionally significant angiogenesis and improves left ventricular systolic and diastolic function in the infarcted myocardium of rats.