2002•Clinical CardiologyOpen access

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

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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.

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Available 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.

Key concepts: Medicine, Neointima, Restenosis, Angioplasty, Intimal hyperplasia, Lumen (anatomy), Cardiology, Stent

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