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Vol. 292, Issue 2, 795-802, February 2000
Angiogenesis Research Center (R.J.L., M.P., F.W.S., J.D.P., M.S.)
and Interventional Cardiology Section (R.J.L.), Department of Medicine,
Harvard Medical School and Beth Israel Deaconess Medical Center,
Boston, Massachusetts; and Chiron Corporation, Emeryville, California
(D.N., D.H.).
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 µg of FGF-2 (n = 10), 200 µg 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.
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