Comparison of three porcine restenosis models: the relative importance of hypercholesterolemia, endothelial abrasion, and stenting.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.