Improved myocardial perfusion and cardiac function by controlled-release basic fibroblast growth factor using fibrin glue in a canine infarct model
摘要Objective: Angiogenic therapy is emerging as a potential strategy for the treatment of ischemic heart disease but is limited by a relatively short half-life of growth factors. Fibrin glue (FG) provides a reservoir for controlledrelease of growth factors. The aim of this study was to evaluate the effects of basic fibroblast growth factor (bFGF)incorporating FG on angiogenesis and cardiac performance in a canine infarct model. Methods: Acute myocardial infarction was induced by ligation of the left anterior descending coronary artery (LAD). Group Ⅰ (n=6) underwent ligation of LAD alone. In Group Ⅱ, transmural channels were created in the infarct area (n=6). In Group Ⅲ, nontransmural channels were created to locate FG cylinders containing bFGF (n=6). Eight weeks after operation, myocardial perfusion was assessed by single photon emission computed tomography, cardiac function by echocardiography, and vascular development by immunohistochemical staining. Results: Total vascular density and the number of large vessels (internal diameter ≥50 μm) were dramatically higher in Group Ⅲ than in Groups Ⅰ and Ⅱ at eight weeks.Only the controlled-release group exhibited an improvement in regional myocardial perfusion associated with lower defect score. Animals in Group Ⅲ presented improved cardiac regional systolic and diastolic functions as well as global systolic function in comparison with the other two groups. Conclusions: Enhanced and sustained angiogenic response can be achieved by controlled-release bFGF incorporating FG within transmyocardial laser channels, thus enabling improvement in myocardial perfusion and cardiac function.
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