Stents For Prevention Of Restenosis Research Articles

UV-modified and dual-catalytic Cu porphyrin-loaded TiO2 nanotubes with enhanced hemocompatibility and prevention of stent restenosis

Implanting vascular stents is regarded as a ground-breaking technique for treating cardiovascular disorders. Thus, advancements in vascular stent technology and stent materials have significant social and economic implications. The development of a surface with bionic endothelial function of nitric oxide (NO) release is always an ideal direction for cardiovascular material modification. However, The NO-release stents will face severe challenges in the oxidative stress microenvironment of atherosclerotic lesions. Excessive reactive oxygen species (ROS) can delay scaffold surface re-endothelialization by causing rapidly oxidative inactivation of NO and by causing endothelial cells (ECs) to undergo apoptosis. Regulating the oxidative stress microenvironment is crucial to address the aforementioned issues. In this study, a composite material that contains ultraviolet (UV)-modified and Copper (II) meso-tetra(4-carboxyphenyl) porphine (CuTPP)-loaded titanium dioxide nanotubes (NTs) was presented. CuTPP can efficiently catalyze the decomposition of ROS and also decompose GSNO into NO. As a unique technique, UV irradiation was used to enhance the anticoagulant properties of the CuTPP-loaded NTs (NTs@Cu). In vivo and in vitro results demonstrated that UV treated NTs@Cu maintained strong biocompatibility, anti-thrombosis, ECs and smooth muscle cells (SMCs) regulation, and anti-inflammatory capabilities. This technique might present a fresh idea for developing brand-new NO-release scaffolds.

Comparative effects of sirolimus-eluting versus bare metal stents on neointimal hyperplasia in balloon-injured external iliac artery of rabbits

The aim of this study was to check effectiveness of drug-eluting stents for prevention of restenosis resulting from neointimal hyperplasia. Twenty-one sirolimus-eluting stents (SESs) and bare metal stents (BMSs; control) were compared by implantation into left and right balloon-injured external iliac arteries of New Zealand White rabbits, respectively. Under general anesthesia and angiography, using 3-mm coronary balloon catheters, stents were successfully deployed. Anticoagulant therapy was not given to any animal. Rabbits were allotted into three groups at 7, 14, and 21 days (7 rabbits in each group). Each stented vessel of sacrificed rabbits was subjected to a resin-embedding technique and methyl methacrylate sections were obtained using a tungsten carbide knife for staining. In histological examination, SESs showed marked reductions in almost all parameters. Morphometric results showed that arteries with SESs had a larger luminal area (P < 0.0001), lower intimal (P < 0.001) and medial (P < 0.001) thickness, and lower intimal index (P < 0.003) as opposed to arteries stented with BMSs. Luminal narrowing in SESs was 0% and reendothelialization was similar in both stented groups (90.48%). SESs showed marked reduction in nonocclusive peristrut fibrin deposition versus BMSs. Thus, the SES was more effective for prevention of restenosis than the BMS in rabbit.

Beyond lipid lowering: pleiotropic effects of statins in heart failure

Beyond lipid lowering: pleiotropic effects of statins in heart failure

Overview of the 2007 Food and Drug Administration Circulatory System Devices Panel Meeting on the Endeavor Zotarolimus-Eluting Coronary Stent

Initial trials comparing stenting with balloon angioplasty demonstrated improved angiographic and clinical outcomes with the former.1–3 The main clinical problem with bare metal stents (BMS) became the development of in-stent restenosis.4–6 Early data suggested that drug-eluting stents (DES) could mitigate, if not abolish, this problem.7–9 Since the approval of DES, these devices have become the predominant stents used in percutaneous coronary interventions, regardless of indication. As of September 2007, the Cypher sirolimus-eluting stent (SES) (Cordis Johnson & Johnson, Miami Lakes, Fla) had been deployed in >3 million patients worldwide,10 and the millionth Taxus paclitaxel-eluting stent (PES) (Boston Scientific, Natick, Mass) was implanted as of January 2005.11 Over the past 2 years, numerous reports of very late stent thrombosis (ST) with first-generation DES have surfaced. This highly morbid complication and data suggesting that death and myocardial infarction (MI) may be more common with DES12,13 have altered the focus of trials and registries working to determine optimal DES use. There is a hope that second-generation DES will be less prone to ST as a result of differences in drug, stent design, and polymer. Medtronic, Inc (Minneapolis, Minn) presented safety and efficacy data to a public meeting of the US Food and Drug Administration (FDA) Circulatory System Devices Panel (CSDP) in October 2007 on its Endeavor zotarolimus-eluting stent (ZES), seeking approval for the indication of treating de novo native coronary lesions ≤27 mm with reference vessel diameters of 2.5 to 3.5 mm. The FDA asked the CSDP to determine whether the data presented demonstrated a reasonable level of safety and effectiveness, with clinical benefits clearly outweighing short- and long-term risks of ZES use. Important efficacy end points included ischemia-driven target lesion revascularization (TLR) or target vessel revascularization (TVR); safety end points included death, MI, and ST. The …

In-office unsedated transnasal balloon dilation of the esophagus and trachea

Since the advent of ultrathin flexible endoscopes with working channels office-based esophagoscopy and tracheobronchoscopy have been undertaken frequently by otolaryngologists. As a natural extension of these diagnostic procedures, more office-based esophageal and tracheal therapeutic procedures are being undertaken. Esophageal and tracheal balloon dilation can be performed in the unsedated patient using a transnasal approach. These transnasal techniques have not been described in the recent literature. Esophageal balloon dilation is a well-accepted technique for gastrointestinal endoscopists, and recent literature has focused on indications (such as cricopharyngeal dysfunction) and the development of removable stents for prevention of restenosis. Pulmonary balloon dilation is likewise well accepted, with recent literature focusing on the timing of intervention and the incidence of tracheobronchial laceration. Office-based esophageal and tracheal balloon dilations in unsedated patients are newly described techniques made possible with thin-caliber transnasal endoscopes.

Update on Drug-Eluting Stents for Prevention of Restenosis

Despite the success of coronary stent implantations in the last decade, in-stent restenosis due to neointimal hyperplasia remains a problem to overcome. Neointimal hyperplasia is a vascular response to stent injury and mainly consists of proliferation of smooth muscle cells and deposition of extracellular matrix. Recently, local drug delivery has been advocated as a potential strategy to prevent in-stent restenosis. Unprecedented results have been obtained in early clinical studies on sirolimus-eluting and paclitaxel-eluting stents. Trials using various pharmaceutical coatings on different coronary stents are ongoing. More types of drug-eluting stents are expected on the market in the near future. Meanwhile, the evaluation of drug-eluting stents is entering the second phase in which the safety and efficacy in more complex lesion subsets and different clinical presentations are being investigated. Results including cost-benefit analyses are expected to have a tremendous impact on the practice of interventional cardiology in the next decade.

Prevention of Carotid Artery Restenosis After Sirolimus-Coated Stent Implantation in Pigs

To test the feasibility of self-expanding drug-coated nitinol stents for prevention of restenosis in an animal model. Stent implantation in the carotid artery (CA) has been shown to be feasible for treatment of CA stenosis. Even though the restenosis rate in CA is reported to be lower than in the coronary and peripheral arteries, problems may arise with increasing numbers of treated patients and lengthier follow-up. After predilatation with 8-mm balloons, 8 Goettinger minipigs were randomly selected to receive a sirolimus-eluting self-expanding nitinol stent (7 mm/80 mm) as well as the same stent without sirolimus/polymer coating in the right or left CA. Aspirin was given starting 3 days before the intervention and administered for an additional 4 weeks. Clopidogrel was administered for 10 days. After 6 weeks, 2 subacute occlusions were observed in both groups. In the remaining vessels, the neointima was significantly reduced by sirolimus/polymer-coated stents (5.9+/-2.5 versus 0.7+/-1.0 mm2). Sirolimus self-expanding nitinol stents may be an effective tool in reducing neointimal formation in CA.

Construction of a surgical stent for posttraumatic nasal synechia

This article describes the clinical and laboratory procedures for the construction of a surgical stent for prevention of restenosis after the surgical opening of posttraumatic synechia of the posterior part of the nasal cavum.

Sirolimus-eluting vs. uncoated stents for prevention of restenosis in small coronary arteries: A randomized trial

Acoustic emission (AE) monitoring is a powerful procedure used to detect and locate damage in mechanically loaded structures, materials, and components. This chapter presents the capability of a new data processing system based on wireless AE equipment that is very useful for long-term monitoring of concrete and masonry structures. Systems based on wireless transmission should be cost-efficient, easy to install, and adaptive to different types of structures and infrastructures. To this purpose, computer-based procedures are implemented. These procedures are performed by automatic AE data processing and used to evaluate the AE data in laboratory tests and in situ monitoring. The final output of the code returns a description, as complete as possible, of damage patterns and their evolution of the monitored structure. In the most critical cases, or in some cases requiring in situ, long observation periods, the AE monitoring method is fine-tuned for a telematics processing procedure of AE data clouds. Finally, to increase the safety of structures and infrastructural networks, the proposed AE monitoring system could also be used to determine the seismic risk of civil constructions and monuments subjected to earthquakes.

Modulation of tissue factor expression by rapamycin and FK-506 in lipopolysaccharide-stimulated human mononuclear cells and serum-stimulated aortic smooth muscle cells

Inflammation is a key pathogenic component of atherosclerosis; it also promotes thrombosis, a process underlying acute coronary events and stroke. Cells present in atherosclerotic plaque show abnormal tissue factor (TF) expression. Macrolides, in addition to their antimicrobial properties, have antiinflammatory effects that might help prevent atherothrombosis. The aim of this study was to determine the effect of an immunosuppressant macrolide, rapamycin (Sirolimus), on the expression of TF and its inhibitor (TFPI) by monocytic cells (human blood mononuclear and THP-1 cells) and human aortic smooth muscle cells, in comparison with FK-506 and azithromycin. In monocytic cells, rapamycin and FK-506 inhibited LPS-induced TF activity, antigen and mRNA expression through a transcriptional mechanism involving NF-kappaB. In smooth muscle cells, rapamycin and azithromycin had no effect on serum-induced TF expression, while FK-506 increased serum-induced TF protein and mRNA expression. TFPI levels in the culture supernatants of serum-stimulated smooth muscle cells were not modified by any of the three macrolides. Rapamycin slightly inhibits TFPI induction by LPS in monocytic cells. In addition to its recently established efficacy in the prevention of stent restenosis, the inhibitory effect of rapamycin on the TF pathway might have interesting therapeutic implications.

Sirolimus-Eluting vs Uncoated Stents for Prevention of Restenosis in Small Coronary Arteries

Percutaneous coronary revascularization of small vessels is associated with a high restenosis rate. Sirolimus-eluting stents reduce restenosis in simple and previously untreated lesions of large coronary arteries, but their outcomes in small vessels have not been adequately investigated. To determine whether sirolimus-eluting stents are associated with a reduced 8-month rate of angiographic restenosis in comparison with an uncoated stent. This was a randomized, multicenter, single-blind, prospective trial performed with 257 patients undergoing percutaneous coronary revascularization for ischemic heart disease, and who had a previously untreated atherosclerotic lesion located in a small segment with a diameter of 2.75 mm or less, in 20 Italian centers between August 2002 and December 2003. Patients were randomly assigned to receive a sirolimus-eluting stent (129 patients) or an uncoated stent having an identical architecture and radiographic appearance (128 patients). The primary end point was the 8-month binary in-segment restenosis rate; secondary end points included procedural success and the 8-month rate of major adverse cardiac and cerebrovascular events. The mean (SD) reference diameter of the treated segment was 2.2 (0.28) mm; the lesion length, 11.84 (6.15) mm. After 8 months, the binary in-segment restenosis rate was 53.1% (60/113) in the patients receiving an uncoated stent and 9.8% (12/123) in those receiving a sirolimus-eluting stent (relative risk [RR], 0.18; 95% confidence interval [CI], 0.10-0.32; P<.001). Fewer patients randomized to sirolimus-eluting stents experienced major adverse cardiac events (12/129 [9.3%] vs 40/128 [31.3%]; RR, 0.30; 95% CI, 0.15-0.55; P<.001) mainly because of a reduction in target lesion revascularization (9/129 [7%] vs 27/128 [21.1%]; RR, 0.33; 95% CI, 0.14-0.70; P = .002) and myocardial infarction (2/129 [1.6%] vs 10/129 [7.8%]; RR, 0.20; 95% CI, 0.01-0.93; P = .04). The use of sirolimus-eluting stents to treat atherosclerotic lesions in small coronary arteries reduces restenosis and may also reduce major adverse cardiac events.

Drug‐eluting stents for secondary prevention of restenosis

Drug‐eluting stents for secondary prevention of restenosis

Use of nitric-oxide-eluting polymer-coated coronary stents for prevention of restenosis in pigs

Restenosis after angioplasty remains an unresolved problem despite an increase in use of coronary stents. It has been theorized that nitric oxide (NO) exerts several actions that can prevent restenosis. These include inhibition of proliferation of smooth muscle cells, prevention of arterial spasms, and decreasing aggregation of platelets in response to exposure to collagen. To determine whether NO coated stents decrease restenosis in a pig balloon injury model. We used coronary stents impregnated with a slow-release precursor of NO in the porcine model of restenosis. Tantalum coil coronary stents (Cordis) were coated with a polymer impregnated with a slow-release precursor of NO. Polymer-coated stents without active precursors were used as controls. Oversized stents were mounted on a delivery balloon and subsequently deployed in the right coronary and left anterior descending arteries of each animal. Repeated recording of angiograms demonstrated that changes in minimum lumen diameter on going from immediately after stenting to 28-day follow-up for the control and NO-eluting-stent groups were similar, namely decreases of 1.89 +/- 0.33 and 2.08 +/- 0.28 mm, respectively. The morphometric results, showing that severe luminal narrowing occurred for both groups, were similar. The percentage area stenoses were 85 +/- 5% for the control group and 84 +/- 6% for the NO-eluting group. Histology demonstrated that profuse formation of neointima and an inflammatory cell infiltrate occurred. Severe diameter stenosis occurred both for control and for treatment groups. The degree of angiographic stenosis was markedly worse than that previously reported for this model. Sustained release of a precursor of NO did not prevent restenosis in this model. This might have been due to a lack of efficacy of nitric oxide or to a profuse and overwhelming stimulatory effect of the polymer in the coated stents.

Quantitative angiographic analysis of stent restenosis in the scripps coronary radiation to inhibit intimal proliferation post stenting (SCRIPPS) trial

To identify luminal dimension changes occurring within the stent alone and within the stent + margin segment, we reviewed the quantitative angiographic results obtained from the Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) trial, a prospective randomized trial assessing the effect of iridium-192 (Ir-192) on the prevention of stent restenosis. Fifty-five patients were randomly assigned to receive Ir-192 or placebo sources after successful intervention. Procedural and 6-month follow-up cineangiograms were quantitatively reviewed in 52 patients to identify changes within the stent and the stent + margin segment. The percent diameter stenosis was lower within the stent than within the stent + margin segment after the procedure (6 ± 22% vs 21± 15%, p <0.0001) and at follow-up (28 ± 29% vs 42 ± 21%, p <0.0001). As a result, a lower restenosis rate was found within the stent than within the stent + margin (25% vs 37%, p <0.0001); isolated stent margin restenosis occurred in 11.5% of lesions. Treatment with Ir-192 reduced restenosis within the stent (8% vs 39%; p = 0.010) and within the stent + margin segment (17% vs 54%; p = 0.010); the reduction in restenosis at the margin only (8.3% vs 14.3%, p = 0.503) was not significant. The lowest relative risk for restenosis resulting from Ir-192 occurred within the stent (0.21; 95% confidecne interval [CI] 0.05 to 0.86) compared with the stent + margin segment (0.31; 95% CI 0.12 to 0.81) or the stent margin (0.58; 95% CI 0.12 to 2.91). In the SCRIPPS trial, 32% of restenosis occurred at the stent margins. Treatment with Ir-192 reduced restenosis primarily within the stent rather than the margin. Whether extending the treatment length to fully include the stent margins will further reduce restenosis requires further study.

Indications and treatment schedules for irradiation of benign diseases: a survey

Background: The interest in the treatment of benign diseases with radiotherapy has grown particularly in the Western part of the world. Questions about the effectiveness and risks of radiotherapy for these disorders have to be answered in the light of new information from clinical research, dose calculations and risk estimates. New indications for irradiation of non-malignant diseases, e.g. vascular disorders, such as macular degeneration and prevention of stent restenosis, are appearing. As a starting point for further discussions and publications in this area, the authors, with the help of the European Society for Therapeutic Radiology and Oncology (ESTRO), performed a survey of current practice and of opinion amongst ESTRO members. Methods: A questionnaire was circulated in 1996 to 1348 institutes listed in the 1995 ESTRO directory asking whether the respondents considered a list of the 28 most common benign disorders as being a good indication for radiotherapy. Details of the frequency of such treatments and of treatment schedules used were requested. Results and conclusions: A large variation in indications and treatment schedules was detected throughout the world. This variation confirms the inadequate information on which such treatments are based and stresses the importance of careful clinical studies and trials as well as clear understanding of any risks involved.

Covered Stents for Prevention of Restenosis

Metallic stents in small vessels go along with a significant risk of restenosis and reocclusion. Different models of stents and covering materials have been purported to prevent intraluminal neointimal proliferation by cover-based closure of the spaces in the wire mesh. Tantalum stents covered with polyethylacrylate/polymethylmethacrylate (PEM) were implanted in the infrarenal aorta of six New Zealand white rabbits by aortotomy and compared with eight rabbits treated with uncovered tantalum stents. For deployment, covered and uncovered stents necessitated a 7-French (F) and 5-F sheath, respectively. In addition, nine human patients with arteriosclerotic lesions of the superficial femoral arteries (stenosis > 5 cm or total occlusion) were treated percutaneously with a Dacron-covered nitinol vascular stent via a 9-F sheath. Patients were followed for a mean of 13.5 months, and control angiography was performed after 6 months. Experimental placement of the tantalum Wiktor stent was feasible technically in all cases. Five of six stents covered with PEM were occluded 3 days after placement despite the intravenous use of heparin and aspirin. In the group with uncovered stents, no area of stenosis greater than 10% was observed. There was a neointimal layer of 89 +/- 68 microns around the stent wires. Stent placement was successful in all patients. In four patients, a hyperergic reaction occurred, resulting in noninfectious periarteriitis. This complication was treated successfully with nonsteroidal antiinflammatory drugs. The primary patency was 50%, and the secondary patency (after application of a second covered stent in two patients) was 63%. The uncovered stent induces little neointimal proliferation around the stent wires. The insertion of stents covered with PEM into the rabbit aorta was accompanied by a strong thrombotic reaction, despite sufficient anticoagulation. Dacron-covered nitinol stents showed a surprisingly high restenosis rate after 9 months of follow-up. Further research concerning the in vivo properties of new covering materials is mandatory before routine vascular clinical application.