Angiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia.
A number of heparin-binding growth factors, including basic (bFGF) and acidic (aFGF) fibroblast growth factors have been shown to promote angiogenesis in vivo. In this study, we employed a sustained-release polymer extravascular delivery system to evaluate the angiogenic efficacy of a novel form of genetically modified aFGF in the setting of chronic myocardial ischemia. Fifteen Yorkshire pigs subjected to Ameroid occluder placement on the left circumflex (LCX) artery were treated with perivascularly administered aFGF in ethylene vinyl acetate (EVAc) polymer (10 micrograms, n = 7) or EVAc alone (controls, n = 8). Seven to nine weeks later, after coronary angiography to document Ameroid-induced coronary occlusion, all animals underwent studies of coronary flow and global and regional left ventricular function. Microsphere-determined coronary flow in the Ameroid-compromised territory was significantly increased in aFGF-treated compared with control animals, and this improvement in perfusion was maintained during ventricular pacing. Left ventricular function studies demonstrated improved global and regional function in aFGF-treated animals. We conclude that local perivascular delivery of genetically modified aFGF results in significant improvement in myocardial flow and regional and global left ventricular function.
Lopez
J J
JJ
Angiogenesis Research Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Edelman
E R
ER
Stamler
A
A
Hibberd
M G
MG
Prasad
P
P
Thomas
K A
KA
DiSalvo
J
J
Caputo
R P
RP
Carrozza
J P
JP
Douglas
P S
PS
Sellke
F W
FW
Simons
M
M
D000818:Animals; D003326:Coronary Circulation; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage*; D006352:Heart Ventricles / Q000473:pathology; D008222:Lymphokines / Q000494:pharmacology; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011994:Recombinant Proteins; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016220:Fibroblast Growth Factor 1