Abstract
Recently, a number of growth factors including basic fibroblast growth factor (bFGF) have been shown to promote angiogenesis in vivo. In this study, we evaluated dose-dependent effect of bFGF administration in the setting of chronic myocardial ischemia. A total of 18 Yorkshire pigs subjected to ameroid occluder placement on the left circumflex artery were randomized to treatment with 10 (n = 6) or 100 μg (n = 5) of bFGF incorporated into heparin-alginate microspheres or inactive control pellets (n = 7). Eight weeks later, all animals underwent angiographic evaluation of collateral development as well as studies of coronary flow and global and regional left ventricular function. Both bFGF groups had significantly higher angiographic collateral index, TIMI flow scores and coronary flow in the ameroid-compromised territory compared with controls. Left ventricular function studies demonstrated improved global and regional function in both fibroblast growth factor groups with significantly better preservation of regional wall motion in high dose (100 μg) bFGF animals. We conclude that local perivascular delivery of bFGF results in significant improvement in myocardial function in the setting of chronic myocardial ischemia.
Footnotes
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Send reprint requests to: Dr. Michael Simons, Cardiovascular Division, Beth Israel Deaconess Medical Center, RW 453, 330 Brookline Avenue, Boston, MA 02215.
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↵1 This work was supported in part by the American Heart Association-Massachusetts Affiliate (501-912) and an National Institutes of Health (NIH) Grant HL-46716 (F.W.S.), National Institutes of Health (NIH) Grant HL-53793 (M.S.), National Institutes of Health (NIH) Grant GM49039, Whittaker Foundation, and Burroughs-Wellcome Fund in Experimental Therapeutics (E.R.E.). J.J.L. and M.S. were also supported by the Clinical Investigator Training Program, Beth Israel Hospital-Harvard/MIT Health Science and Technology, in collaboration with Pfizer, Inc.
- Abbreviations:
- bFGF
- basic fibroblast growth factor
- EVAc
- ethylene vinyl acetate
- LCX
- left circumflex coronary artery
- LAD
- left anterior descending coronary artery
- Received November 12, 1996.
- Accepted March 27, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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