COMPARISON OF 3 PORCINE RESTENOSIS MODELS - THE RELATIVE IMPORTANCE OF HYPERCHOLESTEROLEMIA, ENDOTHELIAL ABRASION, AND STENTING

Background: Porcine models of post-angioplasty restenosis commonly rel y on hypercholesterolemia, endothelial abrasion, and intracoronary ste nting to induce neointimal thickening. Although stenting clearly induc es marked thickening, the influence of pre-stenting endothelial abrasi on, 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 neoi ntimal thickening in three stented swine restenosis models. Methods: T wenty-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 circum flex (CFX) coronary arteries after 2 weeks on this diet, had balloon-e xpandable tantalum coil stents placed in the right coronary artery (RC A), LAD, and CFX after 9 weeks on the diet, and were killed 4 weeks la ter (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 signific ant differences between models in the change of minimal lumen diameter (mm +/- SD) of stented vessels from post-stenting to pre-sacrifice (L AD: 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). L ikewise, morphometric analysis showed no differences in percentage are a stenosis (% +/- SD) over the same time (LAD: 55 +/- 15, 44 +/- 24, a nd 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 = N S). The neointima in each model predominantly consisted of smooth musc le cells and collagen matrix. Conclusions: The degree and nature of co ronary artery neointimal thickening 4 weeks after stenting in normolip emic swine are similar to those in stented swine after 9 weeks on a hi gh-cholesterol diet or 13 weeks on a high-cholesterol diet and early e ndothelial abrasion. The insertion of an intracoronary stent appears t o be the major stimulus to neointimal thickening in these swine models of post-angioplasty restenosis.