Intrapericardial delivery of fibroblast growth factor-2 induces neovascularization in a porcine model of chronic myocardial ischemia.
Therapeutic angiogenesis is a novel approach to the treatment of myocardial ischemia based on the use of proangiogenic growth factors to induce the growth of new blood vessels to supply the myocardium at risk. This study was designed to assess the safety and efficacy of a single intrapericardial injection of basic fibroblast growth factor (FGF-2) in a porcine model of chronic myocardial ischemia. Yorkshire pigs underwent ameroid placement around the left circumflex coronary artery. At 3 weeks, animals were randomized to receive a single intrapericardial injection of either saline (n = 10), 3 mg of heparin (n = 9), 3 mg of heparin + 30 microgram of FGF-2 (n = 10), 200 microgram of FGF-2 (n = 10), or 2 mg of FGF-2 (n = 10). Coronary angiography, microsphere flow, magnetic resonance functional, and perfusion imaging were performed before and 4 weeks after treatment, at which time histologic analysis was also performed on 3 animals in each group. In ischemic pigs, FGF-2 treatment resulted in significant increases in left-to-left angiographic collaterals and left circumflex coronary artery blood flow. These benefits were accompanied by improvements in myocardial perfusion and function in the ischemic territory, as well as histologic evidence of increased myocardial vascularity without any adverse effects. Not one of these benefits was seen in saline- or heparin-treated ischemic animals. A single intrapericardial injection of FGF-2 in a porcine model of chronic myocardial ischemia results in functionally significant myocardial angiogenesis, without any adverse outcomes. This mode of FGF-2 administration may prove to be a useful therapeutic strategy for the treatment of patients with ischemic heart disease.
Laham
R J
RJ
Angiogenesis Research Center, Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. rlaham@caregroup.harvard.edu
Rezaee
M
M
Post
M
M
Novicki
D
D
Sellke
F W
FW
Pearlman
J D
JD
Simons
M
M
Hung
D
D
D000287:Administration, Topical; D000818:Animals; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D006493:Heparin / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011897:Random Allocation; D013552:Swine; D013997:Time Factors
D016222:Fibroblast Growth Factor 2; D006493:Heparin