CHARACTERIZATION OF THE MORPHOLOGICAL AND FUNCTIONAL ALTERATIONS IN RABBIT SUBCLAVIAN ARTERY SUBJECTED TO BALLOON ANGIOPLASTY
CHARACTERIZATION OF THE MORPHOLOGICAL AND FUNCTIONAL ALTERATIONS IN RABBIT SUBCLAVIAN ARTERY SUBJECTED TO BALLOON ANGIOPLASTY
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DOI：
10.1097/00019501-199505000-00008
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发表时间：
1995-05-01
影响因子：
1.8
通讯作者：
GIDDINGS, MJ
中科院分区：
文献类型：
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作者：
HADOKE, P;WAINWRIGHT, CL;GIDDINGS, MJ
背景：许多实验模型已被用于研究再狭窄过程的发病机制，尽管许多模型未能将球囊损伤后的功能和形态改变的时间进程联系起来。我们的目的是建立球囊损伤兔模型，并对这两种变化进行详细的研究。方法：12周龄雄性新西兰大白兔喂饲高脂饮食4周后，造成左锁骨下动脉球囊损伤。术后动物恢复正常饮食，血管成形术后2、7、15、30天处死动物。另外两组动物在高胆固醇喂养4周后(不做血管成形术)或在假血管成形术后2天处死。观察血管成形术对血管收缩[5-羟色胺(5-HT)和KCI]、内皮依赖性(ACh和钙霉素)和非内皮依赖性(SIN-1)血管扩张反应的影响。结果：高胆固醇血症降低了锁骨下动脉对内皮依赖性血管扩张剂卡巴胆碱和钙霉素的反应性，但在正常饮食7d后，这种反应性恢复。血管成形术后30天前，血管塑形动脉对卡巴胆碱的反应一直很低，而血管成形术不影响对钙霉素松弛的恢复。无论是高胆固醇血症还是血管成形术，对5-羟色胺、KCI和SIN-1的反应都没有变化。形态学研究表明，新西兰白兔在7天后出现新生内膜，15天后达到最大。所有新生内膜均为平滑肌肌动蛋白染色。巨噬细胞在7天后在中层出现聚集，15天后在新生内膜中出现，随后逐渐减少。结论：在兔锁骨下动脉中，我们建立了一种完整描述球囊损伤后内膜细胞反应和功能变化的模型。
Background: 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.Methods: 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 KCI] 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.Results: 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, KCI and sin-1 were unchanged by either hypercholesterolaemia or angioplasty. Morphological studies demonstrated the development of neointima in ail 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 from 7 days onwards.Conclusion: 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.