In vitro model to test the thrombogenicity of coronary stents

doi:10.1016/0049-3848(94)90170-8

Thrombosis Research

Volume 75, Issue 6, 15 September 1994, Pages 581-590

https://doi.org/10.1016/0049-3848(94)90170-8 Get rights and content

Abstract

Thrombotic occlusion is a major complication limiting the application of stents in coronary arteries. In an in vitro model we investigated the thrombogenicity of different stent materials and several medical regimens to prevent thrombotic occlusion. Experiments were conducted in a closed system of silicon tubing with circulating citrated platelet rich plasma of healthy volunteers (n=7) and of patients (n=7 for each condition). Patients were either treated with phenprocoumon or with high or low dose heparin in combination with aspirin alone (100 mg) or aspirin (990 mg) plus dipyridamole (225 mg). After placement of tantalum wire stents into the system platelet aggregates were visible after 13.5 ± 3.0 min, and occlusion occurred after 15.0 ± 3.5 min. Similarly, with implanted stainless steel stents aggregation was seen after 13.0 ± 3.5 min and thrombosis occurred after 14.5 ± 3.5 min (p<0.001 vs control without stent). Microscopic examination revealed combined platelet fibrin thrombi occluding the lumen. Platelet components predominately covered stent wires, particularly at crossing points. In all experiments high-dose heparin prevented platelet aggregate formation and stent occlusion independently of additional aspirin or aspirin plus dipyridamole; perfusion time > 60 min (p<0.001 vs no heparin). Low-dose heparin could not prevent clotting. With aspirin alone aggregates were visible after 16.0 ± 4.0 min and clotting occurred after 23.0 ± 5.0 min. In combination with dipyridamole aggregates were visible after 15.5 ± 5.0 min and clotting after 21.0 ± 4.0 min (NS vs aspirin alone). Phenprocoumon prevented platelet aggregate formation and stent occlusion; perfusion time > 60 min. Thus, in our in vitro model both platelet aggregate formation and coagulation play an important role for stent occlusion. High-dose heparin and phenprocoumon prevented both. Low-dose heparin was less effective and could not prevent clotting even in combination with aspirin and dipyridamole.

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A macrofluidic model to investigate the intrinsic thrombogenicity of clinically used stents and develop less thrombogenic stents
2024, Heliyon
Microfluidic blood flow models have been instrumental to study the functions of blood platelets in hemostasis and arterial thrombosis. However, they are not suited to investigate the interactions of platelets with the foreign surfaces of medical devices such as stents, mainly because of the dimensions and geometry of the microfluidic channels. Indeed, the channels of microfluidic chips are usually rectangular and rarely exceed 50 to 100 μm in height, impairing the insertion of clinically used stents. To fill this gap, we have developed an original macrofluidic flow system, which precisely reproduces the size and geometry of human vessels and therefore represents a biomimetic perfectly suited to insert a clinical stent and study its interplay with blood cells. The system is a circular closed loop incorporating a macrofluidic flow chamber made of silicone elastomer, which can mimic the exact dimensions of any human vessel, including the coronary, carotid or femoral artery. These flow chambers allow the perfect insertion of stents as they are implanted in patients. Perfusion of whole blood anticoagulated with hirudin through the device at relevant flow rates allows one to observe the specific accumulation of fluorescently labeled platelets on the stent surface using video-microscopy. Scanning electron microscopy revealed the formation of very large thrombi composed of tightly packed activated platelets on the stents.
Heparanase regulates thrombosis in vascular injury and stent-induced flow disturbance
2012, Journal of the American College of Cardiology
Citation Excerpt :
Stenting induces a complex flow disturbance within the artery. Stent-induced flow profiles are complex and can be highly thrombogenic (14). We used a computational model to characterize the blood flow within our ex vivo flow system.
The purpose of this study was to examine the role of heparanase in controlling thrombosis following vascular injury or endovascular stenting.
The use of endovascular stents are a common clinical intervention for the treatment of arteries occluded due to vascular disease. Both heparin and heparan sulfate are known to be potent inhibitors of thrombosis. Heparanase is the major enzyme that degrades heparan sulfate in mammalian cells. This study examined the role of heparanase in controlling thrombosis following vascular injury and stent-induced flow disturbance.
This study used mice overexpressing human heparanase and examined the time to thrombosis using a laser-induced arterial thrombosis model in combination with vascular injury. An ex vivo system was used to examine the formation of thrombus to stent-induced flow disturbance.
In the absence of vascular injury, wild type and heparanase overexpressing (HPA Tg) mice had similar times to thrombosis in a laser-induced arterial thrombosis model. However, in the presence of vascular injury, the time to thrombosis was dramatically reduced in HPA Tg mice. An ex vivo system was used to flow blood from wild type and HPA Tg mice over stents and stented arterial segments from both animal types. These studies demonstrate markedly increased thromboses on stents with blood isolated from HPA Tg mice in comparison to blood from wild type animals. We found that blood from HPA Tg animals had markedly increased thrombosis when applied to stented arterial segments from either wild type or HPA Tg mice.
Taken together, this study's results indicate that heparanase is a powerful mediator of thrombosis in the context of vascular injury and stent-induced flow disturbance.
Blood triggered corrosion of magnesium alloys
2011, Materials Science and Engineering: B
Citation Excerpt :
However, at present there is a lack of appropriate short and long-term models that mimic in vivo conditions for reliable screening of potential Mg alloys [6,7]. Very few studies have been done in a physiologically accurate system such as fresh human whole blood under flow conditions [8–10]. The aim of this in vitro study was to investigate the corrosion behavior of eight different experimental magnesium alloys after 6 h immersion in a modified Chandler-Loop model with fresh human whole blood and to compare the results with the corrosion data in PBS− as SBF.
Intravascular stents manufactured out of bioabsorbable magnesium (Mg) or Mg-alloys are considered as auspicious candidates for the next stent generation. However, before clinical application numerous physical and biological tests, especially to predict the clinically highly important degradation kinetics in vivo, have to be performed. In a Chandler-Loop model, the initial degradation of eight different magnesium alloys during 6 h in contact with human whole blood was investigated. The magnesium release varied between 0.91 ± 0.33 mg/cm² (MgAl9Zn1) and 2.57 ± 0.38 mg/cm² (MgZn1). No correlation could be found with Mg release data obtained after immersion in simulated body fluid (SBF). This pilot study showed that Mg corrosion is highly influenced by the biological test environment (SBF or blood, etc.) and that a modified Chandler-Loop model with human whole blood may be superior to predict corrosion of Mg alloys under clinical conditions than the SBF models presently used.
Frequency and Consequences of Early In-stent Lesions after Carotid Artery Stent Placement
2009, Journal of Vascular and Interventional Radiology
Citation Excerpt :
Some experimental studies point at a higher thrombogenicity and more intimal proliferation within nitinol stents compared to stainless steel stents (26,27). However, other studies suggest a higher thrombogenicity of stainless steel stents compared with nitinol stents (28–30). Most studies comparing the thrombogenicity of nitinol and stainless steel stents conclude that other factors may also play a role in the thrombogenicity, such as the length and the diameter of the stents.
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.
Radiopacity of current endovascular stents: Evaluation in a multiple reader phantom study
2004, Journal of Vascular and Interventional Radiology
To evaluate the radiopacity of endovascular stents based on the fluoroscopy mode in a phantom of the human pelvis.
The following stents were included in this study: Medtronic AVE Bridge, Medtronic AVE Bridge X, Cordis Covered Nitinol (Covent), Guidant Dynalink, Luminexx, Guidant Megalink, Memotherm Flexx, Palmaz Medium, Palmaz-Schatz Long-Medium, Palmaz Corinthian PQ394Q and PQ294Q, SelfX, SMART without markers, SMART with radiopaque markers, Easy Wallstent. To evaluate radiopacity, images of the stents placed in four different positions (lumbosacral junction left and right, iliosacral joint left and right) of a pelvic phantom were taken at the following modes: spotfilm, continuous fluoroscopy, 15 pulses per second, 7.5 pulses per second, and 3 pulses per second. Images were presented at random to four independent readers and radiopacity scores were assessed: 0 = not visible, 1 = poor visibility, 2 = average visibility, 3 = good visibility, and 4 = very good visibility.
The Covent stent had the highest overall radiopacity score (3.25), followed by the Luminexx (3.04) and the Medtronic AVE Bridge X (2.74) stents. At the spotfilm mode, the best visible stents were the Medtronic AVE Bridge X, the Covent and the Easy Wallstent stents and at the continuous fluoroscopy mode, the Covent, the Luminexx, and the Medtronic AVE Bridge X stents. Decreasing the fluoroscopy mode went hand in hand with a reduction of the radiopacity scores of all stents. At the standard fluoroscopy mode of 7.5 pulses per second, the Covent stent was seen well or very well in 96.9%, followed by the Luminexx (76.9%), and the Medtronic AVE Bridge X (41.25%) stents.
Stent radiopacity directly depends on the fluoroscopy mode; if the pulse frequency decreased, detecting the stents became more difficult. Stent mass correlates with stent radiopacity (eg, Cordis Covered Nitinol, Bridge X). Radiopaque markers may improve stent radiopacity dramatically (eg, Luminexx vs Memotherm Flexx).
Thrombogenicity of various endovascular stent types: An in vitro evaluation
2002, Journal of Vascular and Interventional Radiology
The aim of this study was to evaluate the thrombogenicity of different peripheral stent types in a standardized in vitro model with fresh human whole blood.
Different stents (N = 77; n = 7 of each of 11 types) were implanted in polyvinyl chloride tubing loops and filled with donor blood samples. After 120 minutes of blood circulation, the thrombinantithrombin III complex (TAT) levels, β-thromboglobulin (β-TG) levels, and platelet counts were assessed.
After 2 hours, significant differences were seen. TAT values (±SD) with the investigated stents were 31 μg/mL ± 20 (control, no stent), 328 μg/mL ± 206 (Saxx stent, peripheral medium CrNi31 L), 651 μg/mL ± 760 (Palmaz Corinthian Stent, 316 L stainless steel, electropolished), 1,609 μg/mL ± 1,264 (Palmaz Corinthian Stent, 316 L stainless steel, not electropolished), 810 μg/mL ± 578 (Palmaz Schatz long medium stent), 569 μg/mL ± 347 (Smart Nitinol stent), 1,037 μg/mL ± 577 (Megalink peripheral stent), 543 μg/mL ± 487 (peripheral stent, electropolished), 1,674 μg/mL ± 2,057 (peripheral stent, not electropolished), 3,128 μg/mL ± 1,812 (SelfX Nitinol stent, polished), 5,897 μg/mL ± 2,380 (SelfX Nitinol stent, unpolished), and 1,458 μg/mL ± 887 (bridge stent). The platelet count (×1,000/μL ± SD) was 218 ± 35 (control, no stent), 188 ± 22 (Saxx stent), 187 ± 20 (Palmaz Corinthian stent, electropolished), 135 ± 37 (Palmaz Corinthian stent, not electropolished), 170 ± 24 (Palmaz Schatz stent), 180 ± 36 (Smart Nitinol stent), 159 ± 26 (Megalink peripheral stent), 173 ± 17 (peripheral stent, electropolished), 133 ± 51 (peripheral stent, not electropolished), 123 ± 37 (SelfX Nitinol stent, polished), 52 ± 27 (SelfX Nitinol stent, unpolished), and 130 ± 31 (bridge stent).
This standardized study showed a wide range of platelet activation after stent implantation. Electropolishing clearly reduced the thrombogenicity of the stents.

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PaperIn vitro model to test the thrombogenicity of coronary stents

Abstract

J Am Coll Cardiol

Am Heart J

Am J Cardiol

J Am Coll Cardiol

Thromb Res

Incidence and consequences of periprocedural occlusion

Circulation

Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal angioplasty

Circulation

Transluminal treatment of arteriosclerotic obstruction: description of a new technique and a preliminary report of its application

Circulation

Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty

N Engl J Med

Initial clinical experience with Strecker coronary stent

J Am Coll Cardiol

Strecker coronary stent: Initial multicenter experience

J Am Coll Cardiol

Immediate and late outcome of bail-out coronary stenting

J Am Coll Cardiol

Emergency coronary stenting for abrupt closure and dissection after balloon angioplasty

J Am Coll Cardiol

Angiographic follow-up after placement of an self-expanding coronary stent

N Engl J Med

Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal coronary angioplasty

Circulation

Paper
In vitro model to test the thrombogenicity of coronary stents