Characterization of the morphological and functional alterations in rabbit subclavian artery subjected to balloon angioplasty

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Abstract
A number of experimental models for the study of the pathogenesis of the restenotic process have been developed, although many fail to correlate the time courses of both functional and morphological alterations following balloon injury. Our aim was to develop a rabbit model of balloon injury, which studied both of these alterations in detail. Male New Zealand White rabbits (12 weeks old) were fed a high-cholesterol diet for 4 weeks, after which they were subjected to balloon injury of the left subclavian artery. After surgery the animals were returned to a normal diet and sacrificed 2, 7, 15 or 30 days after angioplasty. Two further groups of animals were sacrificed either after 4 weeks of high-cholesterol feeding (no angioplasty) or 2 days after a sham angioplasty operation. Angioplasty-induced changes in vasoconstrictor [to 5-hydroxytryptamine (5-HT) and KCl] and endothelium-dependent (ACh and calcimycin) and endothelium-independent (sin-1) vasodilator responses were assessed in isolated vessel rings. Morphological analysis of the size and composition of neointima was also made at each timepoint. Hypercholesterolaemia reduced the responsiveness of the subclavian arteries to the endothelium-dependent vasodilators carbachol and calcimycin; however, this responsiveness was restored after 7 days of a normal diet. The response to carbachol remained depressed in angioplastied arteries until 30 days after angioplasty, whereas recovery of relaxation to calcimycin was unaffected by angioplasty. Responses to 5-HT, KCl and sin-1 were unchanged by either hypercholesterolaemia or angioplasty. Morphological studies demonstrated the development of neointima in all rabbits after 7 days, reaching a maximum size after 15 days. All neointima stained for a smooth muscle actin. Accumulation of macrophages appeared in the media after 7 days and was present in the neointima after 15 days, and subsequently declined. Proliferating smooth-muscle cells were evident in the media 2 days after angioplasty, and in the neointima fro 7 days onwards. In the rabbit subclavian artery, we have developed a model that describes fully the temporal development and characteristics of an intimal cellular response and functional changes following balloon injury.

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