The Degree of Neointimal Formation after Stent Placement in Atherosclerotic Rabbit Iliac Arteries is Dependent on the Underlying Plaque

doi:10.1016/S1054-8807(98)00019-2

Cardiovascular Pathology

Volume 8, Issue 2, March–April 1999, Pages 73-80

https://doi.org/10.1016/S1054-8807(98)00019-2 Get rights and content

Abstract

The purpose of this study was to determine the effects of stent placement on the underlying arterial morphology and the relations of stent-vessel wall interactions with subsequent neointimal formation in an atherosclerotic artery. Seven New Zealand White rabbits with experimentally induced atherosclerosis underwent balloon angioplasty (n = 7) and stent placement after balloon angioplasty (n = 7) in the iliac arteries. Histologic analysis of the treated arteries was performed at 28 days to assess device interactions with the artery and the pattern of the neointimal response. The area within the external elastic lamina of the stented vessels was 66% greater than the arteries with balloon angioplasty alone (p = 0.001) which contributed to a significantly greater late lumen area (3.33 ± 0.51 mm² versus 1.33 ± 0.20 mm², p = 0.0028). Neointimal thickness was measured at 220 stent wire sites from 21 sections of stented arteries of which 139 (63%) had underlying plaque and 81 (37%) were adjacent to normal media. Rupture of the internal elastic lamina (IEL) occurred at only 9 (11%) of the 81 stent wire sites over normal media. The mean neointimal thickness was 0.16 ± 0.01 mm for all stent wire sites. The neointimal thickness was greater at the stent wire sites with underlying plaque (0.23 ± 0.01 mm) than at the stent wire sites adjacent to normal media (0.08 ± 0.01 mm) or at sites with rupture of the internal elastic lamina (0.16 ± 0.02 mm, p = 0.0001). The degree of neointimal formation within the stents strongly correlated with the area of the underlying atherosclerotic plaque (r = 0.76, p = 0.0007) and the extent of plaque or medial compression by the struts (r = 0.90, p = 0.006). The present study characterizes stent interactions in a model commonly employed to evaluate novel therapies for the prevention of restenosis. The neointimal response was influenced by the local arterial morphology and correlated with the extent of plaque or medial compression by the stent. These data may be useful for future studies in this model and understanding the mechanism of in-stent restenosis.

Section snippets

Atherosclerotic lesion induction

The animal work was approved by the institutional animal care and use committee of Lilly Research Laboratories and conformed to the position of the American Heart Association on animal research. Seven 3 to 4 kg New Zealand White rabbits were placed on a diet supplemented with 2% cholesterol (Purina Mills Inc.; Richmond, IN) for two weeks. The animals received aspirin 10 mg/kg by mouth the evening prior to balloon injury. Intravenous ketamine (20 mg/kg) and xylazine (4 mg/kg) through a marginal

Histology

The morphology of the atherosclerotic plaque was similar for the stented arteries and those treated with balloon angioplasty alone. The plaque consisted primarily of foam cells and smooth muscle cells. The neointima of the stented arteries contained smooth muscle cells, lipid-rich foam cells, and matrix proteoglycans (Figure 1). Focal plaque disruption or medial dissection was identified in five of the seven (72%) vessels with balloon angioplasty alone. The histomorphologic characteristics of

Discussion

This study describes the effects of stent placement on plaque morphology and the influence of the arterial substrate on neointimal formation in rabbit iliac arteries with atherosclerosis created by arterial injury and dietary hypercholesterolemia four weeks before stenting. Stent placement in rabbit atherosclerotic peripheral arteries resulted in greater vessel expansion than in arteries with balloon angioplasty alone and caused minimal deep vessel wall injury. A majority of the stent struts

Acknowledgements

We thank Debra L. Schuler and Robert M. Christie for expert surgical and animal care assistance and Russ Jones for processing the histology. We are also indebted to Ursula Juengling for assistance with manuscript preparation.

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The single hyperattenuating lesion we found is probably best explained by a calcification pushed through the stent mesh. Such plaque material is considered thrombogenic (20) and could thereby lead to the localized lesions we found. Second, the lesions may consist of thrombus formed due to thrombogenicity of the stent, the native vessel wall, or the plaques that are pushed aside by the stent.
To examine the prevalence of in-stent lesions 1 month after carotid artery stent placement with multidetector computed tomography (CT) angiography and to evaluate their possible causes and their consequences during 1-year follow-up.
Sixty-nine patients with symptomatic carotid artery stenosis underwent multidetector CT angiography of the carotid arteries 1 month after carotid artery stent placement. Patients were followed-up until 1 year after stent placement, when duplex ultrasonography (US) was performed. In-stent lesions were defined as hypo- or hyperattenuating lesions at the stent wall found with multidetector CT. Significant restenosis (70%) at 1 year was defined as a peak systolic velocity of more than 300 cm/sec at duplex US. The Fisher exact test was used to assess the relationship between early in-stent lesions and ischemic events and restenosis.
At 1 month, 14 of the 69 patients (20%) were found to have in-stent lesions. In one patient, the stent was occluded. The other 13 in-stent lesions did not result in significant lumen reduction. In the year following stent placement, no difference in ischemic events was found between patients with (14%) and those without (13%) early in-stent lesions (P = .99). There was no difference in the occurrence of restenosis at 1 year (7% vs 4%, P = .59).
At 1 month after carotid artery stent placement, in-stent lesions are found in about one-fifth of patients. These lesions do not appear to be related to recurrent ischemic events or to restenosis at 1 year.
Echolucent carotid plaques predict in-stent restenosis after bare metal stenting in native coronary arteries
2008, Atherosclerosis
Echolucent carotid plaque is considered to predict coronary events. This study examined whether echolucent carotid plaque may predict in-stent restenosis (ISR) in coronary arteries. This study included 202 patients who had elective and successful percutaneous coronary intervention (PCI) with bare metal stents in de novo lesions of native coronary arteries for symptomatic coronary artery disease (CAD). Carotid plaque echolucency was assessed by ultrasound with integrated backscatter (IBS) analysis (intima-media IBS value minus adventitia IBS) 1 day before PCI. All patients underwent planned coronary angiography (CAG) at 6 months after PCI, or CAG before 6 months due to acute coronary syndromes. ISR (defined as >50% diameter stenosis) was found in 65 (32%) patients. The calibrated IBS values of carotid plaques were inversely correlated with late luminal loss of the stented lesions. Using multivariate logistic regression analysis, the presence of echolucent carotid plaques (≤−13.7dB, arbitrarily determined by an ROC curve) served as an independent predictor of ISR (odds ratio 3.8, 95% CI 1.9–7.3, p = 0.01) and target lesion revascularization (n = 48) (odds ratio 2.8, 95% CI 1.4–5.7, p = 0.01). In conclusion, echolucent carotid plaques with low IBS values were independently and closely associated with ISR in native coronary arteries.
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Several studies indicate that ACE-activity is related to atherosclerosis. We investigated the correlation between ACE-activity, in plasma as well as in the atherosclerotic plaque, and in-stent restenosis.
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The stretching effect during stent implantation without debulking may lead to greater vessel wall injury and thus increase the stimulus for intimal hyperplasia, as has been shown by experimental and clinical studies.16-18 A recent histological study in animals indicated that the degree of in-stent neointimal proliferation is strongly correlated both with the amount of the underlying plaque burden (r = 0.76) and the extent of plaque or medial compression by stent struts (r = 0.90).16 A histological study of human coronary arteries has also shown that stenting accompanied by arterial medial disruption or lipid core penetration by stent struts induces increased arterial inflammation, which is associated with increased neointimal growth.17
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Baseline characteristics of the 2 groups were similar. After intervention, both groups achieved similar LV (140.0 mm³ DCA/stenting vs 135.2 mm³ stenting alone). However, the follow-up ISV and %ISV were significantly smaller in the DCA/stenting group (19.6 ± 12.2 mm³ DCA/stenting vs 44.6 ± 29.5 mm³ stenting alone; P = .00040; 15.3% ± 10.6% DCA/stenting vs 31.5% ± 17.7% stenting alone; P = .00040). Consequently, the DCA/stenting group showed a significantly greater follow-up LV (121.0 ± 51.5 mm³ DCA/stenting vs 91.5 ± 26.7 mm³ stenting alone; P = .016).
Plaque removal with DCA before stenting inhibits in-stent neointimal hyperplasia.

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^☆: This study was funded by Advanced Cardiovascular Systems, Inc., through the American Registry of Pathology, Armed Forces Institute of Pathology, Washington, DC. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

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ArticlesThe Degree of Neointimal Formation after Stent Placement in Atherosclerotic Rabbit Iliac Arteries is Dependent on the Underlying Plaque☆

Abstract

Section snippets

Atherosclerotic lesion induction

Histology

Discussion

Acknowledgements

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

J Am Coll Cardol

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Articles
The Degree of Neointimal Formation after Stent Placement in Atherosclerotic Rabbit Iliac Arteries is Dependent on the Underlying Plaque☆