Grinstead W C, Rodgers G P, Mazur W, French B A, Cromeens D, Van Pelt C, West S M, Raizner A E
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Coron Artery Dis. 1994 May;5(5):425-34. doi: 10.1097/00019501-199405000-00009.
Porcine models of post-angioplasty restenosis commonly rely on hypercholesterolemia, endothelial abrasion, and intracoronary stenting to induce neointimal thickening. Although stenting clearly induces marked thickening, the influence of pre-stenting endothelial abrasion, and pre- and post-stenting hypercholesterolemia, on the degree and nature of post-stenting neointimal thickening is not clear. In order to assess this influence, we compared the quantity and quality of neointimal thickening in three stented swine restenosis models.
Twenty-three Hanford miniature swine completed one of three protocols. Model A animals (n = 9) were fed a cholesterol-raising diet, underwent endothelial abrasion of the left anterior descending (LAD) and circumflex (CFX) coronary arteries after 2 weeks on this diet, had balloon-expandable tantalum coil stents placed in the right coronary artery (RCA), LAD, and CFX after 9 weeks on the diet, and were killed 4 weeks later (total of 13 weeks on diet). Model B animals (n = 7) were also fed the cholesterol-raising diet, underwent stenting after 5 weeks on the diet, and were killed 4 weeks later (total of 9 weeks on diet). Model C animals (n = 7) were fed normal swine food, underwent stenting, and were killed 4 weeks later. Endothelial abrasion was not performed in models B and C.
Quantitative angiography revealed no significant differences between models in the change of minimal lumen diameter (mm +/- SD) of stented vessels from post-stenting to pre-sacrifice (LAD: 1.05 +/- 0.74, 0.75 +/- 0.62 and 1.05 +/- 0.34; CFX: 1.00 +/- 0.65, 0.83 +/- 0.51 and 1.17 +/- 0.38; RCA: 0.99 +/- 0.35, 0.20 +/- 0.34, and 0.94 +/- 0.80 for models A, B, and C, respectively; all P = NS). Likewise, morphometric analysis showed no differences in percentage area stenosis (% +/- SD) over the same time (LAD: 55 +/- 15, 44 +/- 24, and 42 +/- 16; CFX: 54 +/- 12, 55 +/- 17, and 40 +/- 15; RCA: 39 +/- 20, 34 +/- 11, and 26 +/- 13 for models A, B, and C, respectively; P = NS). The neointima in each model predominantly consisted of smooth muscle cells and collagen matrix.
The degree and nature of coronary artery neointimal thickening 4 weeks after stenting in normolipemic swine are similar to those in stented swine after 9 weeks on a high-cholesterol diet or 13 weeks on a high-cholesterol diet and early endothelial abrasion. The insertion of an intracoronary stent appears to be the major stimulus to neointimal thickening in these swine models of post-angioplasty restenosis.
血管成形术后再狭窄的猪模型通常依靠高胆固醇血症、内皮剥脱和冠状动脉内支架置入来诱导内膜增厚。虽然支架置入明显会诱导显著增厚，但支架置入前的内皮剥脱以及支架置入前后的高胆固醇血症对支架置入后内膜增厚的程度和性质的影响尚不清楚。为了评估这种影响，我们比较了三种支架置入猪再狭窄模型中内膜增厚的数量和质量。
23只汉福德小型猪完成了三种方案中的一种。A组动物（n = 9）喂食高胆固醇饮食，在饮食2周后对左前降支（LAD）和左旋支（CFX）冠状动脉进行内皮剥脱，在饮食9周后将球囊扩张钽线圈支架置入右冠状动脉（RCA）、LAD和CFX，4周后处死（饮食共13周）。B组动物（n = 7）也喂食高胆固醇饮食，在饮食5周后进行支架置入，4周后处死（饮食共9周）。C组动物（n = 7）喂食正常猪饲料，进行支架置入，4周后处死。B组和C组未进行内皮剥脱。
定量血管造影显示，从支架置入后到处死前，各模型中支架置入血管的最小管腔直径变化（mm +/- SD）无显著差异（A组、B组和C组的LAD分别为1.05 +/- 0.74、0.75 +/- 0.62和1.05 +/- 0.34；CFX分别为1.00 +/- 0.65、0.83 +/- 0.51和1.17 +/- 0.38；RCA分别为0.99 +/- 0.35、0.20 +/- 0.34和0.94 +/- 0.80；所有P = 无显著性差异）。同样，形态计量分析显示同一时间内狭窄面积百分比（% +/- SD）无差异（A组、B组和C组的LAD分别为55 +/- 15、44 +/- 24和42 +/- 16；CFX分别为54 +/- 12、55 +/- 17和40 +/- 15；RCA分别为39 +/- 20、34 +/- 11和26 +/- 13；P = 无显著性差异）。每个模型中的新生内膜主要由平滑肌细胞和胶原基质组成。
正常血脂猪在支架置入4周后冠状动脉内膜增厚的程度和性质与高胆固醇饮食9周或高胆固醇饮食13周并早期进行内皮剥脱的支架置入猪相似。在这些血管成形术后再狭窄的猪模型中，冠状动脉内支架置入似乎是内膜增厚的主要刺激因素。
