Therapeutic angiogenesis with intramyocardial administration of basic fibroblast growth factor.
BACKGROUND
Basic fibroblast growth factor (bFGF) induces endothelial cell and smooth muscle cell proliferation and stimulates angiogenesis. This study was designed to evaluate the effects of intramyocardial administration of bFGF on myocardial blood flow, angiogenesis, and ventricular function in a canine acute infarction model.


METHODS
Myocardial infarction was induced in 12 dogs by ligation of the left anterior descending coronary artery. Within 5 minutes after coronary occlusion, 100 microg of human recombinant bFGF in 1 mL of saline was injected into the infarct and border zone in 6 dogs, whereas saline alone was used in 6 control dogs. Myocardial blood flow was determined with colored microspheres before and immediately after coronary ligation and again 3, 7, 14, and 28 days after treatment and it was expressed as percent of normal. Angiogenesis was evaluated by immunohistochemical studies 28 days later. Cardiac function was evaluated by repeated echocardiographic measurement.


RESULTS
Treatment with bFGF significantly increased the endocardial blood flow in the border zone (7 days after infarction, 75%+/-7% and 41% +/-7% in the bFGF and control groups, respectively, p<0.01) as well as epicardial blood flow in the infarcted zone. Treatment with bFGF significantly increased the capillary density (39.7+/-2.3 and 22.7+/-1.1 vessels per visual field in the bFGF and control groups, respectively, p<0.01) as well as arteriolar density in the border zone. Treatment with bFGF significantly reduced the change in ratio of thickness of the infarcted wall to the normal wall (44%+/-6% and 26% +/-5% in the bFGF and control groups, respectively, p<0.05). It improved the left ventricular ejection fraction (7 days after infarction, 0.54+/-0.02 and 0.37+/-0.03 in the bFGF and control groups, respectively, p<0.01).


CONCLUSIONS
Intramyocardial administration of bFGF increased the regional myocardial blood flow, reduced thinning of the infarcted region, and improved ventricular function in acute myocardial infarction. Intramyocardial administration of bFGF may be a new therapeutic approach for patients with acute myocardial infarction.
Kawasuji
M
M
Department of Surgery I, Kanazawa University School of Medicine, Japan. kawasuji@med.kanazawa-u.ac.jp
Nagamine
H
H
Ikeda
M
M
Sakakibara
N
N
Takemura
H
H
Fujii
S
S
Watanabe
Y
Y
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D004195:Disease Models, Animal; D004285:Dogs; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000627:therapeutic use*; D007267:Injections; D008863:Microspheres; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D016277:Ventricular Function, Left
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2