The effect of intracoronary fibroblast growth factor‐2 on restenosis after primary angioplasty or stent placement in a pig model of atherosclerosis
Mark J. Post, Roger J. Laham, Richard E. Kuntz, Deborah L. Novicki, Michael Simons
Abstract
Mark J. Post, Roger J. Laham, Richard E. Kuntz, Deborah L. Novicki, Michael Simons
Abstract
BACKGROUND: Therapeutic angiogenesis, if combined with primary percutaneous transluminal coronary angioplasty or stent placement, could improve the outcome of patients suffering from multifocal coronary disease. HYPOTHESIS: Because of the concern that angiogenic growth factors might promote restenosis, we studied the effect of a single intracoronary administration of recombinant fibroblast growth factor (rFGF)-2 on restenosis after balloon angioplasty and stent placement in a pig model of coronary atherosclerosis. METHODS: In 24 Yucatan minipigs, coronary lesions were induced by arterial injury and 3 months of atherogenic diet. After 3 months, repeat catheterization was performed with balloon dilation or stent placement at the injured sites, with a follow-up of 6 weeks. Results were monitored using quantitative angiography, intravascular ultrasound (IVUS), and histomorphometry. RESULTS: Intracoronary rFGF-2 2 microg/kg did not affect neointima formation or remodeling in this model. A small but significant aggravation of late lumen loss was observed in the reference segments of the rFGF-2-treated group. Angiographic and echographic late lumen loss, intimal hyperplasia, and arterial remodeling, as well as histologic neointima were all similar in the rFGF-2- and the vehicle-treated group. Confirming earlier studies from our group and those of others, stented arteries compared with balloon-dilated arteries had increased angiographic late lumen loss, a trend toward increased intimal hyperplasia and decreased remodeling. CONCLUSION: We conclude that rFGF-2 does not aggravate restenosis after balloon dilation or stenting in this pig model of coronary atherosclerosis. Future combinations of angioplasty and therapeutic angiogenesis in a single session should be pursued as a feasible and safe strategy.
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BACKGROUND: Therapeutic angiogenesis, if combined with primary percutaneous transluminal coronary angioplasty or stent placement, could improve the outcome of patients suffering from multifocal coronary disease. HYPOTHESIS: Because of the concern that angiogenic growth factors might promote restenosis, we studied the effect of a single intracoronary administration of recombinant fibroblast growth factor (rFGF)-2 on restenosis after balloon angioplasty and stent placement in a pig model of coronary atherosclerosis. METHODS: In 24 Yucatan minipigs, coronary lesions were induced by arterial injury and 3 months of atherogenic diet. After 3 months, repeat catheterization was performed with balloon dilation or stent placement at the injured sites, with a follow-up of 6 weeks. Results were monitored using quantitative angiography, intravascular ultrasound (IVUS), and histomorphometry. RESULTS: Intracoronary rFGF-2 2 microg/kg did not affect neointima formation or remodeling in this model. A small but significant aggravation of late lumen loss was observed in the reference segments of the rFGF-2-treated group. Angiographic and echographic late lumen loss, intimal hyperplasia, and arterial remodeling, as well as histologic neointima were all similar in the rFGF-2- and the vehicle-treated group. Confirming earlier studies from our group and those of others, stented arteries compared with balloon-dilated arteries had increased angiographic late lumen loss, a trend toward increased intimal hyperplasia and decreased remodeling. CONCLUSION: We conclude that rFGF-2 does not aggravate restenosis after balloon dilation or stenting in this pig model of coronary atherosclerosis. Future combinations of angioplasty and therapeutic angiogenesis in a single session should be pursued as a feasible and safe strategy.
Key concepts: Medicine, Neointima, Restenosis, Angioplasty, Intimal hyperplasia, Lumen (anatomy), Cardiology, Stent