Intravascular stents: a new technique for tissue processing for histology, immunohistochemistry, and transmission electron microscopy

Malik, Nadim; Gunn, Julian; Holt, Cathy M.; Shepherd, L; Francis, Sheila; Newman, Christopher M.; Crossman, David C.; Cumberland, D.C.

doi:10.1136/hrt.80.5.509

Cited by 57 publications

(50 citation statements)

References 26 publications

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“…5 This may be for the most part because of the technical challenge to perform immunohistochemistry in hard resin-embedded specimen. 7,8 The need for deplastification of the grinded sections to uncover antigens aggravates the complexity of specimen processing. 8 In addition, establishment of primary antibodies in resin-embedded specimen requires far more time and effort as compared to paraffin wax-embedded specimen.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Characterization of Neotissues and Tissue Reactions to Septal Defect–Occlusion Devices

Foth

Quentin

Michel‐Behnke

et al. 2009

Circ: Cardiovascular Interventions

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Background-We sought to evaluate tissue reactions within and at the surface of devices for interventional therapy of septal defects and to identify antigen characteristics of neotissues. Methods and Results-Atrial or ventricular septal defect-occlusion devices (Amplatzer, nϭ7; Cardioseal/Starflex, nϭ3) were processed using a uniform protocol after surgical removal from humans (implantation time, 5 days to 4 years). Devices were fixed in formalin and embedded in methylmethacrylate. Serial sections were obtained by sectioning with a diamond cutter and grinding, thus saving the metal/tissue interface for histologic evaluation.Immunohistochemical staining was performed using conventional protocols. Superficial endothelial cells stained positive for von Willebrand factor. Within the newly formed tissues, fibroblast-like cells were identified with a time-dependent expression of smooth muscle cell maturation markers (smooth muscle actin, smooth muscle myosin, h-caldesmon, and desmin) beside extracellular matrix components. Neovascularization of the newly formed tissues was demonstrated with the typical immunohistochemical pattern of capillaries and small vessels. Inflammatory cells could be identified as macrophages (CD68ϩ) and both T-type and B-type lymphocytes (CD3ϩ, CD79ϩ). Conclusions-This is the first presentation of results from serial immunohistochemical staining of a collection of explanted human septal-occlusion devices. A time-dependent maturation pattern of the fibroblast-like cells in the neotissues around the implants could be described. Neoendothelialization was seen in all specimens with implantation times of 10 weeks or more. The time course of neoendothelialization, as seen in our study, further supports the clinical practice of anticoagulant or antiplatelet therapy for 6 months after implantation. This time interval should be sufficient to prevent thromboembolic events due to thrombus formation at the foreign surface of cardiovascular implants.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical Characterization of Neotissues and Tissue Reactions to Septal Defect–Occlusion Devices

Foth

Quentin

Michel‐Behnke

et al. 2009

Circ: Cardiovascular Interventions

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“…Analysis of samples containing both soft tissues and metal stents is technically demanding. 11 Stent strut removal and embedding with ordinary paraffin or snap-freezing result in loss of constituents and artifacts from tissue rupture. In situ implants can be embedded in resin polymers, such as methylmethacrylate (MMA), and processed by hard-tissue cutting.…”

Section: See Covermentioning

confidence: 99%

Angiogenesis, Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor-BB Expression, Iron Deposition, and Oxidation-Specific Epitopes in Stented Human Coronary Arteries

Bräsen

Kivelä

Röser

et al. 2001

ATVB

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Abstract-Pathogenesis of in-stent restenosis remains poorly understood because information from human histopathologic studies is scarce. We used an improved saw-grinding and cutting method on methacrylate-embedded samples containing metal stents, which allows in situ hybridization and immunohistochemical analysis of in-stent restenosis. Twenty-one samples were collected 3 hours to 3 years after stenting from 6 patients aged 36 to 81 years. Except in very early samples collected within hours after the stent deployment, neovascularization was present in all segments studied. At advanced stages, extensive neovascularization was located mainly at the luminal side of the stent struts and was only rarely accompanied by inflammatory cells. The neovessels colocalized with vascular endothelial growth factor (VEGF)-A mRNA and protein expression as well as with iron deposits and oxidation-specific epitopes, which imply the presence of chronic oxidative stress. VEGF-A expression was detected in the same areas containing macrophages, endothelial cells, and, to a lesser extent, smooth muscle cells, which also showed platelet-derived growth factor-BB expression. We conclude that in-stent restenosis features neovascularization, VEGF-A and platelet-derived growth factor-BB expression, and iron deposition, which is most probably derived from microhemorrhages. These mechanisms may play an important role in the development of neointimal thickening and could provide useful targets for the prevention and treatment of in-stent restenosis. Key Words: in-stent-restenosis Ⅲ immunohistochemistry Ⅲ in situ hybridization Ⅲ pathology Ⅲ methylmethacrylate embedding P ercutaneous transluminal coronary angioplasty (PTCA) is the treatment of choice in short single coronary lesions. Acute complications, dissections, and early recoil can be treated or avoided with intracoronary stents, which also reduce the incidence of late restenosis. Nevertheless, angiographic restenosis is seen in 20% to 30% of ideal lesions treated with stents. 1,2 The angiographic restenosis rate with more complex lesions is even higher. 3 Treatment of in-stent restenosis by balloon dilation, rotablation, and coronary atherectomy leads to unsatisfactory results in at least 50% of the cases. 4 Thus, prevention of in-stent restenosis is an important goal. See coverIn-stent restenosis is thought to be a reparative process resembling wound healing, involving a cascade of traumatic, thrombotic, granulating, and proliferative phases as well as late remodeling, with final accumulation of smooth muscle cells and matrix components. 5,6 Glycoprotein IIb/IIIa antagonists aiming at blocking early platelet deposition/thrombus formation and the proliferation and migration of smooth muscle cells reduced but failed to fully inhibit in-stent restenosis. 7,8 The amount of medial damage and stent oversizing have been shown to be correlated with the degree of in-stent restenosis, suggesting that the extent of vessel trauma plays a crucial role in in-stent restenosis. 9,10 One of the major probl...

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“…The focus is on the methodology used for the development of the model rather than on its results. Model validation will entail the use of a porcine dataset (Malik et al 1998;Dean et al 2005). This fully documented histological archive comprises hundreds of arterial sections (figure 1c,d ) of stented porcine arteries.…”

Section: Multiscale Modelling and Simulation In Biomedicinementioning

confidence: 99%

The application of multiscale modelling to the process of development and prevention of stenosis in a stented coronary artery

Evans

Lawford

Gunn

et al. 2008

Phil. Trans. R. Soc. A.

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The inherent complexity of biomedical systems is well recognized; they are multiscale, multiscience systems, bridging a wide range of temporal and spatial scales. While the importance of multiscale modelling in this context is increasingly recognized, there is little underpinning literature on the methodology and generic description of the process. The COAST (complex autonoma simulation technique) project aims to address this by developing a multiscale, multiscience framework, coined complex autonoma (CxA), based on a hierarchical aggregation of coupled cellular automata (CA) and agent-based models (ABMs). The key tenet of COAST is that a multiscale system can be decomposed into N single-scale CA or ABMs that mutually interact across the scales. Decomposition is facilitated by building a scale separation map on which each single-scale system is represented according to its spatial and temporal characteristics. Processes having wellseparated scales are thus easily identified as the components of the multiscale model. This paper focuses on methodology, introduces the concept of the CxA and demonstrates its use in the generation of a multiscale model of the physical and biological processes implicated in a challenging and clinically relevant problem, namely coronary artery in-stent restenosis.

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Intravascular stents: a new technique for tissue processing for histology, immunohistochemistry, and transmission electron microscopy

Cited by 57 publications

References 26 publications

Immunohistochemical Characterization of Neotissues and Tissue Reactions to Septal Defect–Occlusion Devices

Immunohistochemical Characterization of Neotissues and Tissue Reactions to Septal Defect–Occlusion Devices

Angiogenesis, Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor-BB Expression, Iron Deposition, and Oxidation-Specific Epitopes in Stented Human Coronary Arteries

The application of multiscale modelling to the process of development and prevention of stenosis in a stented coronary artery

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