Improved myocardial perfusion and cardiac function by controlled-release basic fibroblast growth factor using fibrin glue in a canine infarct model.
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 controlled-release 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, non-transmural 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.
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. spnie@126.com
Shao-ping
SP
Nie
Xiao
X
Wang
Shi-bin
SB
Qiao
Qiu-tang
QT
Zeng
Ju-quan
JQ
Jiang
Xiao-qing
XQ
Liu
Xiang-ming
XM
Zhu
Guo-xiang
GX
Cao
Chang-sheng
CS
Ma
D000818:Animals; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004285:Dogs; D005169:Factor VIII / Q000032:analysis; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006321:Heart / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D055414:Myocardial Perfusion Imaging; D015899:Tomography, Emission-Computed, Single-Photon
D003692:Delayed-Action Preparations; D015718:Fibrin Tissue Adhesive; D016222:Fibroblast Growth Factor 2; D005169:Factor VIII