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Biomedical subjects

H M van Beusekom

Publications and source records attributed to H M van Beusekom.

At least 19 recordsLinked to original sources
PubMed2001

"Edge Effect" of (32)p radioactive stents is caused by the combination of chronic stent injury and radioactive dose falloff.

BACKGROUND: Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side. METHODS AND RESULTS: Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01). CONCLUSIONS: The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.

Animals↗
PubMed2000

Coronary stent implantation changes 3-D vessel geometry and 3-D shear stress distribution.

Mechanisms of in-stent restenosis are not fully understood. Shear stress is known to play a role in plaque and thrombus formation and is sensitive to changes in regional vessel geometry. Hence, we evaluated the regional changes in 3-D geometry and shear stress induced by stent placement in coronary arteries of pigs.Methods. 3-D reconstruction was performed, applying a combined angiographic and IVUS technique (ANGUS), from seven Wallstents (diameter 3.5 (n=3) and 5mm (n=4)), which were implanted in seven coronary arteries of five pigs. This 3-D geometry was used to calculate locally the curvature, while the shear stress distribution was obtained by computational fluid dynamics. Local changes in shear stress were obtained at the entrance and exit of the stent for baseline (0. 65+/-0.22 ml/s) and hyperemic flow (2.60+/-0.86 ml/s) conditions. Results. After stent implantation, the curvature increased by 121% at the entrance and by 100% at the exit of the stent, resulting in local changes in shear stress. In general, at the entrance of the stent local maxima in shear stress were generated, while at the exit both local maxima and minima in shear stress were observed (p<0.05). Additionally, the shear stress at the entrance and exit of the stent were correlated with the local curvature (r: 0.30-0.84).Conclusion. Stent implantation changes 3-D vessel geometry in such a way that regions with decreased and increased shear stress occur close to the stent edges. These changes might be related to the asymmetric patterns of in-stent restenosis.

Animals↗
PubMed2000

Biocompatibility of phosphorylcholine coated stents in normal porcine coronary arteries.

OBJECTIVE: To improve the biocompatibility of stents using a phosphorylcholine coated stent as a form of biomimicry. INTERVENTIONS: Implantation of phosphorylcholine coated (n = 20) and non-coated (n = 21) stents was performed in the coronary arteries of 25 pigs. The animals were killed after five days (n = 6), four weeks (n = 7), and 12 weeks (n = 8), and the vessels harvested for histology, scanning electron microscopy, and morphometry. MAIN OUTCOME MEASURES: Stent performance was assessed by studying early endothelialization, neointima formation, and vessel wall reaction to the synthetic coating. RESULTS: Stent thrombosis did not occur in either group. Morphometry showed no significant differences between the two study groups at any time point. At five days both the coated and non-coated stents were equally well endothelialised (91% v 92%, respectively). At four and 12 weeks there was no difference in intimal thickness between the coated and non-coated stents. Up to 12 weeks postimplant the phosphorylcholine coating was still discernible in the stent strut voids, and did not appear to elicit an adverse inflammatory response. CONCLUSION: In this animal model the phosphorylcholine coating showed excellent blood and tissue compatibility, unlike a number of other polymers tested in a similar setting. Given that the coating was present up to 12 weeks postimplant with no adverse tissue reaction, it may be a potential candidate polymer for local drug delivery.

Animals↗
PubMed1998

Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries.

OBJECTIVE: To compare percutaneous transluminal coronary angioplasty (PTCA) and stent implantation with respect to the long-term changes they induce in the newly formed endothelium in porcine coronary arteries by studying both morphological and functional parameters of the endothelium at 2 weeks and 3 months after intervention. BACKGROUND: Problems affecting PTCA or stent implantation have been overcome to a large extent by means of better techniques and the availability of new drugs. Late problems, however, still exist in that restenosis affects a large number of patients. With an increasing number of patients being treated with stents, the problem of in-stent restenosis is of even greater concern, as this seems difficult to treat. A functional endothelial lining is thought to be important in controlling the growth of the underlying vascular tissue. We hypothesized that the enhanced neointimal hyperplasia observed after stenting is associated with a more pronounced and prolonged endothelial dysfunction. METHODS: Arteries were analyzed using a dye-exclusion test and planimetry of permeable areas. Thereafter, the arteries were processed for light and scanning electron microscopy for assessment of morphology and proliferative response. RESULTS: Leakage of the endothelium for molecules such as Evans blue-albumin as well as prolonged endothelial proliferation is observed as late as 3 months after the intervention, and is more pronounced after stenting. Permeability is associated with distinct morphologic characteristics: endothelial retraction, the expression of surface folds, and the adhesion of leukocytes. CONCLUSIONS: Stenting especially decreases long-term vascular integrity with respect to permeability and endothelial proliferation, and is associated with distinct morphologic characteristics.

Angioplasty, Balloon, Coronary↗
PubMed1998

Increasing arterial wall injury after long-term implantation of two types of stent in a porcine coronary model.

AIMS: There is increased late loss in luminal diameter following long-term coronary stenting, compared with balloon angioplasty. We evaluated short- and long-term vessel wall injury after experimental implantation of two stent designs as well as balloon angioplasty and their relationship to neointimal hyperplasia. METHODS AND RESULTS: Wiktor stents and Palmaz-Schatz stents were implanted in normal coronary arteries of pigs (balloon/artery ratio: 0.9-1.1). In control coronary arteries, balloon angioplasty was performed. At 1, 4 and 12 weeks, the vessel injury score, neointimal thickness and inflammatory response were assessed by histology. The vessel injury score increased over time in both Wiktor and Palmaz-Schatz stents: 0.9 +/- 0.1, 1.5 +/- 0.5 and 1.7 +/- 0.6 (mean +/- SD) for Wiktor stents and 0.7 +/- 0.2, 1.0 +/- 0.1 and 1.2 +/- 0.3 for Palmaz-Schatz stents at 1, 4 and 12 weeks follow-up, respectively. No increase in injury was seen in balloon angioplasty controls. Inflammation was seen in both stented groups but was absent 12 weeks after balloon angioplasty. No strong correlation between injury and neointimal thickness was apparent. CONCLUSION: Stents induce chronic injury in contrast to balloon angioplasty. Stent design (coil vs slotted tube) as well as inflammation may influence vessel response.

Analysis of Variance↗
PubMed1997

Foreign body contamination during stent implantation.

The treatment of coronary artery disease using stents has become a widely accepted technique. However, the inadvertent co-implantation of contaminating factors with the stent has received little attention. We studied histological cross-sections of stented porcine coronary arteries and observed contamination of some vessels with surgical glove powder and textile fibres. The contaminating particles were associated with a foreign body reaction. Such a reaction could delay the wound-healing response of a stented vessel and thereby prolong the period in which subacute thrombosis could occur. It is also proposed that air contamination could affect the thrombogenicity of the stent. Appropriate measures should be followed to reduce the chance of contamination occurring.

Angioplasty, Balloon↗
PubMed1996

Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries.

BACKGROUND: With the thrombogenic tendency and permanent implant nature of metallic stents, synthetic polymers have been proposed as candidate materials for stents and local drug delivery designs. We investigated the biocompatibility of several synthetic polymers after experimental placement in the coronary artery. METHODS AND RESULTS: Five different biodegradable polymers (polyglycolic acid/polylactic acid [PGLA], polycaprolactone [PCL], polyhydroxybutyrate valerate [PHBV], polyorthoester [POE], and polyethyleneoxide/polybutylene terephthalate [PEO/ PBTP]) and three nonbiodegradable polymers (polyurethane [PUR], silicone [SIL], and polyethylene terephthalate [PETP]) were tested as strips deployed longitudinally across 90 degrees of the circumferential surface of coil wire stents. Appropriately sized polymer-loaded stents were implanted in porcine coronary arteries of 2.5- to 3.0-mm diameter. Four weeks after implantation, stent patency was assessed by angiography followed by microscopic examination of the coronary arteries. The biodegradable PCL, PHBV, and POE and the nonbiodegradable PUR and SIL evoked extensive inflammatory responses and fibrocellular proliferation (thickness of tissue response: 0.79 +/- 0.22, 1.12 +/- 0.01, 2.36 +/- 0.60, 1.24 +/- 0.36, and 1.43 +/- 0.15 mm, respectively). Less but still severe responses were observed for the biodegradable PGLA and PEO/PBTP (0.46 +/- 0.18 and 0.61 +/- 0.23 mm, respectively) and for the nonbiodegradable PETP (0.46 +/- 0.11 mm). CONCLUSIONS: An array of both biodegradable and nonbiodegradable polymers has been demonstrated to induce a marked inflammatory reaction within the coronary artery with subsequent neointimal thickening, which was not expected on the basis of in vitro tests. The observed tissue response may be attributable to a combination of parent polymer compound, biodegradation products, and possibly implant geometry.

Animals↗
PubMed1996

Reduction in thrombotic events with heparin-coated Palmaz-Schatz stents in normal porcine coronary arteries.

BACKGROUND: The use of stents improves the result after balloon coronary angioplasty. Thrombogenicity of stents is, however, a concern. In the present study, we compared stents with an antithrombotic coating with regular stents. METHODS AND RESULTS: Regular stents were placed in coronary arteries of pigs receiving no aspirin (group 1; n = 8) or aspirin over 4 weeks (group 2, n = 10) or 12 weeks (group 3, n = 9). Stents coated with heparin (antithrombin III uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group 4). The other animals received aspirin and coated stents with a heparin activity of 12 pmol antithrombin III/stent (group 5, n = 10) or 20 pmol/stent (group 6, n = 10; group 7, n = 10). Quantitative arteriography was performed at implantation and after 4 (groups 1, 2, and 4 through 6) or 12 weeks (groups 3 and 7). In an additional 5 animals, five regular and five coated stents (20 pmol/stent) were placed and explanted after 5 days for examination of the early responses to the implants. Thrombotic occlusion of the regular stent occurred in 9 of 27 in groups 1 through 3. However, in 0 of 30 of the animals receiving high-activity heparin-coated stents (groups 5 through 7), thrombotic stent occlusion was observed (P < .001). Histological analysis at 4 weeks showed that the neointima in group 6 was thicker compared with its control group 2 (259 +/- 104 and 117 +/- 36 microns, P < .01), but at 12 weeks the thickness was similar (152 +/- 61 and 198 +/- 49 microns, respectively). Comparison at 5 days suggested delayed endothelialization of the coating. CONCLUSIONS: High-activity heparin coating of stents eliminates subacute thrombosis in porcine coronary arteries.

Angioplasty, Balloon, Coronary↗
PubMed1994

Stenting or balloon angioplasty of stenosed autologous saphenous vein grafts in pigs.

In a model of early and aggressive vein graft stenosis in pigs, an intervention was performed with a single stent (n = 12 grafts), multiple stents (n = 6), or balloon angioplasty (n = 6), while grafts with mild stenoses were left untreated (n = 8). Four weeks after intervention, angiography showed that grafts with single stents, balloon angioplasty, or untreated grafts had patency rates of 92%, 83%, and 83%, respectively. Grafts receiving multiple stents, however, showed only a 17% patency rate (p < 0.05). Balloon dilatation or placement of a single stent improved the angiographic minimal diameter by 0.6 +/- 0.2 and 0.8 +/- 0.3 mm, respectively, over the short term, but this gain was lost during the follow-up period. Multiple stents showed a similar gain (0.5 +/- 0.2 mm) but more loss occurred during the follow-up period (2.4 +/- 0.2 mm). Histology revealed no significant differences between the treatment groups except for the prolonged presence of thrombus remnants in association with the stent wires. In conclusion, single stents and balloon angioplasty show good patency in early saphenous vein graft narrowing but multiple stents show a high occlusion rate.

Anastomosis, Surgical↗
PubMed1993

Mechanical features and in vivo imaging of a polymer stent.

A polyethylene-terephthalate (PETP, polyester), self-expanding, braided mesh stent has been developed for percutaneous (coronary) arterial implantation. In vitro measurements showed that the radial pressure delivered by this device was similar to a self-expanding, stainless steel stent. Due to hysteresis-like behaviour, it proved necessary to mount the polymer stent on the delivery system immediately before the placement procedure, and to select a diameter in the unconstrained condition, which was 60% larger than the diameter of the target vessel. Eight polyester stents were implanted in peripheral arteries of four pigs. Except for heparin during the implantation procedure, antithrombotic or antiplatelet drugs were not administered. After four weeks repeat angiography revealed that one of the stents was subtotally occluded. At autopsy, two other stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative angiographic assessment showed that the mean luminal diameters at the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 2.7 +/- 0.5 mm at four weeks after implantation. Intravascular ultrasound (IVUS) examination after 4 weeks could identify the individual struts of the stents, as well as their length. In addition, a description of the extent of neointimal hyperplasia was feasible. The IVUS assessment was validated by histological examination. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at four weeks. Imaging of stents by angiography and IVUS provided complementary information.

Angiography↗
PubMed1993

Histology after stenting of human saphenous vein bypass grafts: observations from surgically excised grafts 3 to 320 days after stent implantation.

OBJECTIVES: To gain insight into the mechanism of stenting in humans and its short- and long-term implications, we studied the vascular wall of saphenous vein aortocoronary bypass grafts after implantation of the Wallstent. BACKGROUND: The implantation of a stent in aortocoronary bypass grafts may provide an alternative solution for revascularization in patients who are poor candidates for reoperation. Because human histopathologic findings after stenting with the Wallstent have not previously been described in detail, we examined graft segments that were surgically retrieved from 10 patients (21 stents) at 3 days to 10 months after implantation of the stent. METHODS: The grafts were examined by a combination of the following techniques: light microscopy, immunocytochemistry and both scanning and transmission electron microscopy. RESULTS: Early observations revealed that large amounts of platelets and leukocytes adhered to the stent wires during the first few days. At 3 months, the wires were embedded in a layered new intimal thickening, consisting of smooth muscle cells in a collagenous matrix. In addition, foam cells were abundant near the wires. Extracellular lipids and cholesterol crystals were found after 6 months. Smooth muscle cells and extracellular matrix formed the predominant component of restenosis. This new intimal thickening was lined with endothelium, in some cases showing defect intercellular junctions and abnormal adherence of leukocytes and platelets as late as 10 months after implantation. CONCLUSIONS: This type of stent is potentially thrombogenic and seems to be associated with extracellular lipid accumulation in venous aortocoronary bypass grafts.

Coronary Artery Bypass↗
PubMed1992

Development of a polymer endovascular prosthesis and its implantation in porcine arteries.

A polyethylene-terephthalate braided mesh stent has been developed for application in the (coronary) arterial tree. In vitro measurements showed that the radial pressure delivered by this device was in the same range as that of a stainless steel stent. Hysteresis-like behavior, however, occurred after constraining the polyester stent for a period of only 15 minutes on a delivery system for percutaneous implantation. This implies that the polymer stent must be mounted on this delivery system immediately before the placement procedure, and that either a diameter in the unconstrained condition must be selected, which is considerably larger than the diameter of the target vessel, or stent expansion has to be enhanced by balloon expansion. Taking into account the results obtained during the in vitro studies, we investigated the angiographic patency and histologic features after implantation of this polyester stent in peripheral arteries of pigs. In four animals eight stents were placed. Except for heparin during the implantation procedure only, antithrombotic or antiplatelet drugs were not administered. After 4 weeks repeat angiography was performed. Angiography revealed that five of the six correctly placed stents were patent. At autopsy, two additional patent stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative assessment showed that the mean luminal diameters of the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 3.1 +/- 0.3 mm at 4 weeks after implantation. Histology demonstrated an inflammatory reaction of variable severity around the stent fibers. Quantitative histologic measurements showed that the thickness of the neointima was 114 +/- 38 mum after 4 weeks. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. Hysteresis-like behavior of polyester stents, however, influences the selection of the nominal stent diameter as well as the forces exerted to the vessel wall. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at 4 weeks. The extent of neointimal proliferation was similar to that observed after placement of metal stents in swine, despite the presence of a more pronounced inflammatory reaction.

Angioplasty, Balloon, Coronary↗
PubMed1991

Stenting of coronary arteries: has a modern Pandora's box been opened?

Interventional cardiology has recently witnessed the growth of several alternatives to percutaneous transluminal angioplasty, including coronary stenting. Although stenting appears to be useful in treating abrupt closure after coronary angioplasty, its effectiveness in limiting the complex processes responsible for late restenosis is much less certain. Pathologic examination of stented human saphenous bypass grafts shows extensive deposits of platelets, fibrin and leukocytes along the stent wires within the 1st week and formation of a neointima of variable thickness after 3 months without evidence of foreign body reaction. The long-term effects of continuous barotrauma induced by the expanded stent remain unknown. It is difficult to assess the relative merits of the new devices, but stenting has several theoretic advantages. It seems less disruptive to the underlying architecture of the vessel wall and enjoys favorable theoretic and effective expansion ratios. Wide-spread clinical acceptance for stenting will depend on demonstrating that its safety, efficacy and cost efficiency are superior to those of balloon angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1991

Coronary stenting with a new, radiopaque, balloon-expandable endoprosthesis in pigs.

BACKGROUND: Intracoronary stents may be effective when used as "bail-out" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs. METHODS AND RESULTS: In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks. CONCLUSIONS: Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited.

Angiography↗
PubMedDate not supplied

Mechanisms of drug loading and release kinetics.

In an effort to overcome the limitations of local drug delivery associated with the use of catheters, drug-loaded stents have been developed. Loading of such stents is achieved through either drug absorption (incorporation into a matrix) or drug adsorption (surface layering). The type of drug binding determines the elution profile/release kinetics of the drug, while the therapeutic target determines both the choice of drug used and the manner in which it is bound, i.e. eluting or non-eluting. While non-eluting stents have clinically reduced thrombotic complications following stent implantation, current experimental work concentrates on the use of eluting stents to combat restenosis.

Absorption↗
PubMedDate not supplied

Synthetic polymers.

For several decades, synthetic polymers have been the subject of study for vascular applications. Several materials have been tested to date, both for coating and replacing metal stents. While conflicting data between some of these studies exist, these may in part be related to characteristics secondary to the synthetic polymer itself: surface characteristics (roughness, porosity, contaminants), bulk, fragmentation and degradation rate in the case of bioabsorbable polymers. Knowledge of the healing characteristics of the coated stents or stent grafts are essential for successful long-term results.

Animals↗