Enhanced expression of vascular growth factors and cell proliferation by controlled-releasing basic fibroblast growth factors in canine myocardium / 中国组织工程研究

ABSTRACT

BACKGROUND: Experimental evidence suggests that growth factors can promote myocardial angiogenesis, but the effect and mechanism of basic fibroblast growth factor (bFGF) in controlled release delivered via fibrin glue has not been fully recognized.OBJECTIVE: To evaluate the effect of controlled-release bFGF delivered via fibrin glue in the myocardium on the expressions of vascular growth factors and cell proliferation in the local acute myocardial infarct area in canines, and assess the therapeutic effect of this strategy.DESIGN: Completely randomized controlled experiment.SETTING: Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences; Department of Cardiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology; Shanghai Xinxing Blood Product Research Institute.MATERIALS This experiment was carried out in the Laboratory of Animal Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, and the Experimental Animal Center of Chinese PLA General Hospital between June 2001 And March 2003.Twelve clean healthy adult mongrel dogs of either sex were selected and randomized into transmyocardial laser revascularization group and bFGF group with 6 in each group.METHODS: With appropriate anesthesia, the chest of the dog was opened and the left anterior descending (LAD) branch of the coronary artery was ligated to establish acute myocardial infarction (AMI) model.The dogs were then randomized into transmyocardial laser revascularization group to receive transmural myocardial penetration 30 minutes after AMI and bFGF group with non-transmural myocardial penetration 30 minutes after AMI and subsequent injection of bFGF-containing fibrin glue into the channel. The expressions of vascular epithelial growth factor (VEGF), transforming growth factor beta 1 (TGFβ1) and proliferating cell nuclear antigen (PCNA) in the loacl ischemic myocardium were examined immunohistochemically (IHC) at postoperative 18 weeks.MAIN OUTCOME MEASURES: Quantitative IHC analysis of VEGF,TGFβ1 and the PCNA expressions in the local ischemic myocardia in transmyocardial laser revascularization group and bFGF group.RESULTS: Five dogs in the transmyocardial laser revascularization group and 6 in the bFGF group survived the operations. Quantitative IHC analysis revealed obviously larger positive area stained for myocardial VEGF,TGFβ1 and PCNA in bFGF group than in transmyocardial laser revascularization group (t=-7.505, -2.690 and -6.895, P ＜ 0.05), and the average absorbance of PCNA staining in bFGF group was greater than that in the transmyocardial laser revascularization group (t= -5.271, P ＜ 0.05).CONCLUSION: Controlled-releasing bFGF delivered in the myocardium can increase local expressions of the vascular growth factors in the ischemic myocardium and enhance cell proliferation, promoting revascularization after AMI.