EFFECTS OF A SINGLE ADMINISTRATION OF FIBROBLAST GROWTH-FACTOR ON VASCULAR WALL REACTION TO INJURY

Expansion of the vascular wall through formation of neointimal fibromuscular lesions is the basic mechanism underlying stenosis of vascular grafts, restenosis of arteries treated by balloon angioplasty, and other major cardiovascular problems. This study examined the effect of a single, systemic, low dose of basic fibroblast growth factor (bFGF) on formation of neointimal fibromuscular lesions in response to injury. New Zealand white rabbits (n = 76) were subjected to balloon injury of the abdominal aorta. Forty-five rabbits were given a single intravenous dose of bFGF (0.5 mu g/kg) immediately after injury, and 31 rabbits were given only the vehicle solution as controls. After 2 (n = 15), 5 (n = 21), 14 (n = 29), or 28 (n = 11) days the rabbits were sacrificed. Those rabbits receiving the single administration of bFGF exhibited significantly greater intimal thickening (intima/media ratio) than the control group at 5 days (mean +/- standard error of the mean, 0.091 +/- 0.009 versus 0.058 +/- 0.006; p < 0.002), but not at 14 or 28 days. These results were achieved without any significant differences in mitotic indices, as determined by a mitostatic method, between the two groups at any postinjury interval examined. The findings suggest that a single systemic dose of exogenous bFGF has a relatively long term effect on enhancing the neointimal response to vascular injury. Therefore, local control of endogenous bFGF may be useful in limiting formation of vascular neointimal fibromuscular lesions, thus improving the long-term results of vascular grafts, balloon angioplasty, and other cardiovascular procedures.