Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation, whereas VEGF exacerbated neointimal thickening without improving collateral flow.
RCT (n=39)
randomized
Does short-term treatment with bFGF or VEGF improve myocardial collateral perfusion and induce neointimal accumulation in a canine model of coronary occlusion and vascular injury?
Short-term systemic treatment with bFGF enhances coronary collateral development without increasing neointimal hyperplasia, supporting its potential clinical investigation in ischemic heart disease.
BACKGROUND: We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. METHODS AND RESULTS: Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n = 9), VEGF 0.72 mg (n = 9), or saline (n = 10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n = 6) or saline (n = 5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury. CONCLUSIONS: Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease.
Lazarous et al. (1996) conducted an RCT in ameroid-induced occlusion of the left circumflex coronary artery (n=39). basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) vs. saline was evaluated on maximal collateral flow and neointimal accumulation. Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation, whereas VEGF exacerbated neointimal thickening without improving collateral flow.