A novel model of accelerated intimal hyperplasia in the pig iliac artery

Abstract

There is no good animal model of large artery injury-induced intimal hyperplasia (IH). Those available are reproducible, providing only a few layers of proliferating cells or have the disadvantage of the presence of a metallic stent that complicates histology evaluation. This study was designed to develop a new, simple model of accelerated IH based on balloon injury in conjunction with disruption of the Internal Elastic Lamina (IEL) in pig external iliac arteries. Iliac artery injury (n = 24) was performed in 12 Yorkshire pigs divided in two groups: Group I (n = 10), overdistention injury induced by an oversized non-compliant balloon; Group II (n = 14), arterial wall disruption by pulling back an isometric cutting balloon (CB) followed by stretching with a compliant Fogarty Balloon (FB). At two weeks, arteries were processed for morphometric analysis and immunohistochemistry (IHC) for smooth muscle cells (SMC) and proliferating cell nuclear antigen (PCNA). When comparing the two groups, at 2 weeks, arteries of group II had a higher incidence of IH (100%vs. 50%, P = 0.0059), increased intimal areas (2.54 ± 0.33 mm(2) vs. 0.93 ± 0.36 mm(2) , P = 0.004), increased intimal area/Media area ratios (0.95 ± 0.1 vs. 0.28 ± 0.05; P < 0.0001) and decreased lumen areas (6.24 ± 0.44 vs. 9.48 ± 1.56, P = 0.026). No thrombosis was noticed in Group II. Neointima was composed by proliferating SMC located with the highest concentration in the area of IEL disruption (IHC). Arterial injury by pulling back CB and FB induces significant IH in pig iliac arteries by two weeks without thrombosis. This model is superior to the classical overdistention non-compliant model and should be useful and cost-effective for preclinical testing of procedures designed to inhibit IH in large peripheral arteries.

Histopathological Evidence of Adventitial or Medial Injury Is a Strong Predictor of Restenosis During Directional Atherectomy for Peripheral Artery Disease

“…It has been demonstrated in a porcine model that balloon injury in conjunction with disruption of the internal elastic lamina is associated with accelerated intimal hyperplasia vs overdistention without disruption of the internal elastic lamina. 9 This is consistent with our analysis of human peripheral restenotic plaques, which suggested that a breach in the structural integrity of the internal elastic lamina between the tunica media and the tunica intima is associated with increased neointimal proliferation, inflammation, and cellularity compared to de novo atherosclerosis. 10 This correlates with a biological response of cellular proliferation and repair resulting from deep injury leading to restenosis.…”

Multiscale Modeling in Vascular Disease and Tissue Engineering

“…This was due to the nonlinear stress-stiffening response of arteries where higher expansions increased the level of arterial stresses exponentially. This prediction was verified by comparison to experimental studies which show that the stent expansion diameter is an important predictor of the level of intimal growth [37][38][39][40]. In addition the model predicted a higher restenosis rate for thicker stent struts compared to thinner struts which is consistent with the outcome of many clinical studies [41][42][43][44].…”

An Experimental Study to Replace the Thoracic Descending Aorta for Pigs with a Self-Made Sutureless Blood Vessel

“…The pathological examination and the electron microscopy showed that the inner wall of the artificial vessel wall was covered with layer of endothelial cells and vascular smooth cells without any thrombosis. Pig's intimal proliferation may be much more intense than that in human being [ 19 ], which means that the healing capacity may be greater than that in a diseased human aorta, but the difference may not enough to impede we conclude, from these biopsy findings, that the SMSBV has a good biocompatibility.…”