Stented Blood Vessels Research Articles

Forensic expert evaluation problems of early and late complications of interventional methods of treating coronary heart disease (systematic literature review)

This article focuses on current concepts of ischemic heart disease, its interventional treatment, pathomorphology of early and late postoperative complications, and forensic aspects in evaluation of restenosis of a stented blood vessel.

Electrical Conductance Device for Stent Sizing.

The minimum stent area (MSA) has been clinically established as a significant predictor of restenosis, thrombosis, and ischemia using intra-vascular ultrasound (IVUS). Unfortunately, IVUS measurements are far from routine because of significant cost of IVUS, the training required, the subjectivity of image interpretation and the time added to the procedure. The objective of this study is to verify the accuracy of a conductance catheter for stent sizing. Here, we introduce an easy and entirely objective device and method for real time determination of MSA. A 10 kHz, 35 μA rms current is passed through the external electrodes of an intravascular catheter while the conductance is measured across a separate set of electrodes. Both phantom and ex vivo validations of metal stent sizing in five porcine carotid arteries were confirmed. The accuracy of the measurements were found to be excellent in phantoms (root mean square, rms, of 3.4% of actual value) and in ex-vivo vessels (rms = 3.2% of measured value). An offset of conductance occurs when a conductive metal stent (e.g., bare metal stent) is deployed in the vessel, while the slope remains the same. This offset is absent in the case of drug eluting stent where the metal is coated (i.e., insulated) or non-metal bioresorbable stent. The present device makes easy, accurate and reproducible measurements of the size of stented blood vessels within 3.2% rms error. This device provides an alternative method to sizing of stent (i.e., MSA) in real-time without subjective interpretation and with less cost than IVUS.

Waves and fluid-solid interaction in stented blood vessels.

This paper focuses on the modelling of fluid–structure interaction and wave propagation problems in a stented artery. Reflection of waves in blood vessels is well documented in the literature, but it has always been linked to a strong variation in geometry, such as the branching of vessels. The aim of this work is to detect the possibility of wave reflection in a stented artery due to the repetitive pattern of the stents. The investigation of wave propagation and possible blockages under time-harmonic conditions is complemented with numerical simulations in the transient regime.

Wave reflection and transmission in multiply stented blood vessels.

Closed circulatory systems display an exquisite balance between vascular elasticity and viscous fluid effects, to induce pulse-smoothing and avoid resonance during the cardiac cycle. Stents in the arterial tree alter this balance through stiffening and because a periodic structure is introduced, capable of interacting with the fluid in a complex way. While the former feature has been investigated, the latter received no attention so far. But periodic structures are the building blocks of metamaterials, known for their ‘non-natural’ behaviour. Thus, the investigation of a stent's periodic microstructure dynamical interactions is crucial to assess possible pathological responses. A one-dimensional fluid–structure interaction model, simple enough to allow an analytical solution for situations of interest involving one or two interacting stents, is introduced. It is determined: (i) whether or not frequency bands exist in which reflected blood pulses are highly increased and (ii) if these bands are close to the characteristic frequencies of arteries and finally, (iii) if the internal structure of the stent can sensibly affect arterial blood dynamics. It is shown that, while the periodic structure of an isolated stent can induce anomalous reflection only in pathological conditions, the presence of two interacting stents is more critical, and high reflection can occur at frequencies not far from the physiological values.

Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review

Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept "bio-adaption" between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed.

Magnetically enhanced cell delivery for accelerating recovery of the endothelium in injured arteries

Arterial injury and disruption of the endothelial layer are an inevitable consequence of interventional procedures used for treating obstructive vascular disease. The slow and often incomplete endothelium regrowth after injury is the primary cause of serious short- and long-term complications, including thrombosis, restenosis and neoatherosclerosis. Rapid endothelium restoration has the potential to prevent these sequelae, providing a rationale for developing strategies aimed at accelerating the reendothelialization process. The present studies focused on magnetically guided delivery of endothelial cells (EC) functionalized with biodegradable magnetic nanoparticles (MNP) as an experimental approach for achieving rapid and stable cell homing and expansion in stented arteries. EC laden with polylactide-based MNP exhibited strong magnetic responsiveness, capacity for cryopreservation and rapid expansion, and the ability to disintegrate internalized MNP in both proliferating and contact-inhibited states. Intracellular decomposition of BODIPY558/568-labeled MNP monitored non-invasively based on assembly state-dependent changes in the emission spectrum demonstrated cell proliferation rate-dependent kinetics (average disassembly rates: 6.6±0.8% and 3.6±0.4% per day in dividing and contact-inhibited EC, respectively). With magnetic guidance using a transient exposure to a uniform 1-kOe field, stable localization and subsequent propagation of MNP-functionalized EC, markedly enhanced in comparison to non-magnetic delivery conditions, were observed in stented rat carotid arteries. In conclusion, magnetically guided delivery is a promising experimental strategy for accelerating endothelial cell repopulation of stented blood vessels after angioplasty.

Design and validation of a novel ferromagnetic bare metal stent capable of capturing and retaining endothelial cells.

Rapid healing of vascular stents is important for avoiding complications associated with stent thrombosis, restenosis, and bleeding related to antiplatelet drugs. Magnetic forces can be used to capture iron-labeled endothelial cells immediately following stent implantation, thereby promoting healing. This strategy requires the development of a magnetic stent that is biocompatible and functional. We designed a stent from the weakly ferromagnetic 2205 stainless steel using finite element analysis. The final design exhibited a principal strain below the fracture limit of 30% during crimping and expansion. Ten stents were fabricated and validated experimentally for fracture resistance. Another 10 stents magnetized with a neodymium magnet showed a magnetic field in the range of 100-750mG. The retained magnetism was sufficiently strong to capture magnetically-labeled endothelial cells on the stent surfaces during in vitro studies. Magnetically-labeled endothelial cell capture was also verified in vivo after 7 days following coronary implantation in 4 pigs using histological analysis. Images of the stented blood vessels showed uniform endothelium formation on the stent surfaces. In conclusion, we have designed a ferromagnetic bare metal stent from 2205 stainless steel that is functional, biocompatible, and able to capture and retain magnetically-labeled endothelial cells in order to promote rapid stent healing.

Isolation of high-quality RNA from stented blood vessels

Stents have become a standard of care for the treatment of coronary artery disease. A series of cellular and molecular processes contribute to the vascular response following stent placement. For the purpose of local gene expression studies, metallic stent struts are usually removed from the vessel wall with forceps under a dissection microscope prior to RNA extraction. Main drawbacks of the manual dissection are that it may cause additional tissue damage and compromise the quality of RNA through prolonged tissue handling. In this technical note, we report the recovery of high-quality RNA from atherosclerotic vessels with stent struts left in situ.

Site‐specific gene delivery to stented arteries using magnetically guided zinc oleate‐based nanoparticles loaded with adenoviral vectors

Gene therapeutic strategies have shown promise in treating vascular disease. However, their translation into clinical use requires pharmaceutical carriers enabling effective, site-specific delivery as well as providing sustained transgene expression in blood vessels. While replication-deficient adenovirus (Ad) offers several important advantages as a vector for vascular gene therapy, its clinical applicability is limited by rapid inactivation, suboptimal transduction efficiency in vascular cells, and serious systemic adverse effects. We hypothesized that novel zinc oleate-based magnetic nanoparticles (MNPs) loaded with Ad would enable effective arterial cell transduction by shifting vector processing to an alternative pathway, protect Ad from inactivation by neutralizing factors, and allow site-specific gene transfer to arteries treated with stent angioplasty using a 2-source magnetic guidance strategy. Ad-loaded MNPs effectively transduced cultured endothelial and smooth muscle cells under magnetic conditions compared to controls and retained capacity for gene transfer after exposure to neutralizing antibodies and lithium iodide, a lytic agent causing disruption of free Ad. Localized arterial gene expression significantly stronger than in control animal groups was demonstrated after magnetically guided MNP delivery in a rat stenting model 2 and 9 d post-treatment, confirming feasibility of using Ad-loaded MNPs to achieve site-specific transduction in stented blood vessels. In conclusion, Ad-loaded MNPs formed by controlled precipitation of zinc oleate represent a novel delivery system, well-suited for efficient, magnetically targeted vascular gene transfer.

Fatigue life prediction of cardiovascular stent using finite element method

Failure of a stent due to fatigue may result in loss of radial support of the stented blood vessel or in perforation of the vessel by the stent struts. Fatigue analysis, combined with stress analys...

Short-term effects of fully bioabsorbable PLLA coronary stents in a porcine model

Although metallic stents are effective in preventing acute occlusion and reducing late restenosis after coronary angioplasty, many concerns still remain. In this report, short-term effects of fully bioabsorbable sirolimus-loaded poly-l-lactic acid (PLLA) stents (Xinsorb) were evaluated in a porcine coronary model. Commercially available PLLA-coated sirolimus-eluting stents (Excel) were used as controls. The purpose of this study was to assess technical feasibility, biocompatibility, and impact on coronary stenosis of fully bioabsorbable PLLA stents. Our preliminary experience suggested that Xinsorb stents have succeeded in preventing elastic recoil and suppressing neointimal formation for the first 90 days and only mildly delayed the endothelialisation process of the stented blood vessel. Coronary stenosis following Xinsorb and Excel stent implantations after 30 and 90 days was 18.6 ± 5.2% versus 21.4 ± 7.2% and 24.5 ± 4.7% versus 27.7 ± 5.6%, respectively (p > 0.05). Both Xinsorb and Excel stents required approximately 1–3 months for re-endothelialization of the inner wall of stented blood vessels. These data provided additional insights into the mechanism and efficacy of fully bioabsorbable PLLA stents in normal porcine coronary arteries while raising questions regarding the potential durability of this novel medical device. Long-term follow-up will be required to validate the long-term efficacy of fully bioabsorbable PLLA stents.

Magnetic nanoparticles for targeted vascular delivery

Magnetic targeting has shown promise to improve the efficacy and safety of different classes of therapeutic agents by enabling their active guidance to the site of disease and minimizing dissemination to nontarget tissues. However, its translation into clinic has proven difficult because of inherent limitations of traditional approaches inapplicable for deep tissue targeting in human subjects and a need for developing well-characterized and fully biocompatible magnetic carrier formulations. A novel magnetic targeting scheme based on the magnetizing effect of deep-penetrating uniform fields is presented as an example of a strategy providing a potentially clinically viable solution for preventing injury-triggered reobstruction of stented blood vessels (in-stent restenosis). The design of optimized magnetic carrier formulations and experimental results showing the feasibility of uniform field-controlled targeting for site-specific vascular delivery of small-molecule pharmaceuticals, biotherapeutics, and cells are discussed in the context of antirestenotic therapy. The versatility of this approach applicable to different classes of therapeutic agents exerting their antirestenotic effects through distinct mechanisms prompts exploring the utility of uniform field-mediated magnetic stent targeting for combination therapies with enhanced efficiencies and improved safety profiles. Additional improvements in terms of site specificity and protracted carrier retention at the site of injury may be expected from the development and use of magnetic carriers exhibiting affinity for arterial wall-specific antigens.

Improved protocol for processing stented porcine coronary arteries for immunostaining

Percutaneous coronary intervention has resulted in a paradigm shift in the treatment of coronary artery disease and myocardial infarction. However, neither bare-metal stents nor polymer-coated drug-eluting stents represent ideal therapies at this time due to the undesired in-stent stenosis or delayed thrombosis. Hence there is pressing clinical need for greater understanding of the cellular mechanisms involved. It is hoped that this in turn will provide insight into designing and developing the next generation of stents. Although immunohistochemistry and immunofluorescence are appropriate tools in understanding the molecular histology, performing these techniques on stented blood vessels is technically challenging because of poor permeability of antibodies into the stented blood vessels which are embedded in methacrylate-based resins and inadequate image resolution due to autofluorescence. Hence there is a need to develop techniques which can facilitate immunohistochemistry/immunofluorescence procedures on stented blood vessel cross-sections. In this study we describe an improved protocol for processing stented porcine coronary arteries for immunostaining with smooth muscle cell, endothelial cell, monocyte and macrophage markers. We first identified the optimal conditions for resin embedding of stented artery and cross sectioned the vessels using high speed precision wafering diamond blade. The sections were then ground using two levels of water sandpaper on a Metaserve 2000 grinder to achieve the desired thickness. For immunostaining, we developed a novel deplasticization protocol which favors optimal antibody permeabilization. Our protocol not only provides feasibility of improved immunostaining of stented artery sections but also results in high quality images.

Effect of endovascular stent strut geometry on vascular injury, myointimal hyperplasia, and restenosis

Purpose: Early restenosis and the development of myointimal hyperplasia in stented blood vessels have been attributed to deep vascular injury with fracture of the internal elastic lamina (IEL). The purpose of this study was the evaluation of the vascular wall response to superficial injury (without IEL rupture) after balloon angioplasty and intravascular stent placement in porcine arteries and the determination of the effect of stent strut geometry on the degree of vessel injury and early restenosis. Methods: Balloon-expandable stainless-steel stents were placed into the iliac arteries of 10 Sinclair miniature swine that had been fed an atherogenic diet. A Palmaz stent, with rectangular struts and smooth corners, was randomly assigned to one iliac artery (group 1), and a novel stent, which was designed and manufactured in the laboratory with thicker struts and sharper corners specifically to induce large wall stress concentrations, was placed in the contralateral iliac artery (group 2). Intravascular ultrasound scan was used in all deployments to ensure accurate balloon sizing and to avoid stent overexpansion and deep vascular injury. At 90 days after implantation, the animals were killed, the stented vessels harvested, and histomorphometric analysis performed. Results: Deployment of novel stents in group 2 resulted in a statistically higher incidence rate of deep vascular injury (fracture of the IEL) compared with group 1, despite identical balloon size used for deployment (with Student t test, P < .05). Vessels with deep injury showed a 10-fold increase in myointimal thickening compared with those vessels in which the IEL remained intact. A statistically higher restenosis rate was observed for group 2 (33.5% ± 19.90%) compared with group 1 (20.39% ± 14.70%). For both stent designs, there was a trend toward lower degrees of restenosis within the mid-portion of the stent. For superficially injured arteries in both groups, no correlation was observed between the amount of vessel wall/medial layer compression and the development of restenosis from myointimal hyperplasia. Conclusion: Maintenance of an intact IEL is an important factor in the prevention of myointimal hyperplasia and restenosis in stented porcine iliac arteries. The alteration of stent strut height and geometry does not significantly affect restenosis and the development of myointimal hyperplasia in vessels with superficial injury. Superficial injury elicits a response that is independent of stent strut geometry and vessel wall compression. Stent strut profile may, however, increase local vessel wall stress concentrations, leading to IEL rupture and an exaggerated response to injury. (J Vasc Surg 2002;36:143-9.)

Effects of abciximab on the acute pathology of blood vessels after arterial stenting in nonhuman primates.

This study was designed to assess the effect of abciximab on platelet and leukocyte deposition 60 min after stent insertion in nonhuman primates. Although it is well established that abciximab improves both short- and long-term clinical outcomes after stent placement, there have been no studies assessing its effect on early platelet and leukocyte deposition. Cynomolgus monkeys were pretreated with aspirin and either saline or a 0.4 mg/kg bolus of abciximab, and then subjected to angioplasty and Palmaz-Schatz stent placement in the common iliac artery or abdominal aorta. After 60 min, animals were euthanized and the stented artery was evaluated by immunohistochemistry and morphometry. Complete occlusion of the stented vessel with a thin fibrin(ogen) meshwork and trapped blood occurred in two saline-treated and two abciximab-treated animals. In the four remaining saline-treated animals, a layer of erythrocytes trapped in a network of fibrin(ogen) was noted close to the vessel wall, and this was covered by a layer of large, irregular platelet thrombi. Leukocytes formed a monolayer on top of the platelets and near stent struts. In the four remaining abciximab-treated animals, the mean erythrocyte area was 65% smaller (p = 0.070), the platelet aggregate area was 89% smaller (p = 0.049) and the luminal area was 59% larger (p = 0.004). A monolayer of leukocytes also formed on top of the platelets and near stent struts. In control stented blood vessels in this study, platelet thrombi formed not at the vessel wall, but on top of an erythrocyte-rich layer, and platelets recruited leukocytes. Abciximab decreased the size of platelet thrombi, but did not prevent leukocyte recruitment.

1131 ステントが内挿された動脈瘤付き血管内の拍動流の数値シミュレーション

1131 ステントが内挿された動脈瘤付き血管内の拍動流の数値シミュレーション