Vessel wall reactions to endovascular stent implantation

In order to gain insight in the effects of stenting, we studied the process of wound healing and the short- and long-term effect of these permanently present foreign bodies. Both thrombogenic and less thrombogenic metals were evaluated with respect to thrombogenicity and tissue response. Synthetic polymers were evaluated with respect to improving the haemocompatibility and tissue-compatibility profile of these devices. Stenting of normal porcine arteries. In Chapter 2, a balloon-expandable tantalum stent is described, tested in normal porcine coronary arteries for one and four weeks, and an indication is given of the process of wound healing and of the extent of intimal hyperplasia in these arteries. In chapter 3 a self-expanding stainless steel stent was tested in normal porcine coronary arteries. Luminal change was assessed at one, four, and twelve weeks using quantitative angiography, while histologic analysis was performed at twelve weeks only. Additionally, the efficacy of a polymer coating as well as pharmacological treatment (antiplatelet and anti-coagulant treatment) aimed at reducing acute thrombotic complications and intimal hyperplasia was studied. In an attempt to improve some of the features of stents, early thrombogenicity and barotrauma, a polymeric stent was developed and tested in vitro and in vivo and the results are discussed in Chapter 4, Stenting of vein grafts. Using a model of early vein graft narrowing in pigs, stenting was studied to assess the potential benefit of single and mnltiple stent implantation, compared to plain balloon angioplasty (Chapter 5). Stenting of both diseased and healthy arteries in animals of similar age and using the same stent, enables the assessment of behaviour of this stent under different circumstances. Pathologic examination of human saphenous vein bypass grafts treated with the self-expanding stainless steel stent (used in pigs in Chapter 3), is discussed in Chapters 6 and 7. This allowed for a comparison between the effect of stents when implanted in healthy porcine coronary arteries, porcine arteriovenous grafts and diseased human arteriovenous grafts. Vascular (dys)function. To assess long-term effects of stenting, a physiological study was undertaken to determine vascular function (Chapter 8). Aogiotensin metabolism in stented porcine coronary arteries was studied, as angiotensin IT is implicated as a growth factor or as a modifier of growth response of smooth muscle cells

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

Thrombotic complication during intracoronary imaging

Intracoronary imaging with intracoronary ultrasound and coherence tomography is often used in the follow-up of coronary stent implantation. The present case shows an infrequent complication of these procedures, suggesting our continued attention to the selective use of these invasive procedures

Endovascular procedures cause transient endothelial injury but do not disrupt mature neointima in Drug Eluting Stents

Extensive application of coronary intravascular procedures has led to the increased need of understanding the injury inflicted to the coronary arterial wall. We aimed to investigate acute and prolonged coronary endothelial injury as a result of guidewire use, repeated intravascular imaging and stenting. These interventions were performed in swine (N = 37) and injury was assessed per coronary segment (n = 81) using an Evans Blue dye-exclusion-test. Scanning electron microscopy and light microscopy were then used to visualize the extent and nature of acute (<4 hours) and prolonged (5 days) endothelial injury. Guidewire and imaging injury was mainly associated with denudation and returned to control levels at 5 days. IVUS and OCT combined (Evans Blue staining 28 ± 16%) did not lead to more acute injury than IVUS alone (33 ± 15%). Stent placement caused most injury (85 ± 4%) and despite early stent re-endothelialization at 5 days, the endothelium proved highly permeable (97 ± 4% at 5 days; p < 0.001 vs acute). Imaging of in-stent neointima at 28 days after stent placement did not lead to neointimal rupture. Guidewire, IVUS and OCT induce acute endothelial cell damage, which does not increase during repeated imaging, and heals within 5 days. Interestingly, endothelial permeability increases 5 days post stenting despite near complete re-endothelialization

Arterial stenting with self-expandable and balloon-expandable endoprostheses

Coronary angioplasty is complicated by acute occlusion (within 24 hours) and late restenosis (within 6 months) in 2-5% and 20-40% of the cases, respectively. Vascular endoprostheses (stents) may provide the cardiologist with a solution to some of these complications. Several stent-devices are now available for experimental and clinical evaluation. In this study we describe our experience with two metallic stents in normal arteries of swine. Self-expandable, stainless steel stents (3.5 mm diameter) were implanted in 17 peripheral arteries, eight of which were deendothelialized by prior balloon angioplasty. Following implantation, the animals received antithrombotic therapy with acenocoumarol and aspirin (8 stents), or aspirin alone (9 stents). After 1 week repeat angiography was performed, which showed patency of all stented arteries. Microscopy showed complete covering by neointima, 80 μm in thickness. This self-expandable stent (SES) and a balloon-expandable stent (BES), constructed of tantalum, were implanted in normal coronary arteries. SES (3.0 and 3.5 mm) receiving animals were treated with coumadines (10 stents) or received no antithrombotic treatment (16 stents) after implantation. BES receiving animals were also not treated (10 stents). Three untreated animals with SES died suddenly within 48 hours. Postmortem examination showed partial or complete thrombosis of all six stents in these animals, resulting in a patency rate of 62% after 1 week. All animals with SES, which were treated with coumadines, and all animals with BES (untreated) had patent stents after one week. It is concluded that SES implanted in normal coronary arteries of pigs, which do not receive additional antithrombotic treatment, show a 38% occlusion rate within 48 hours, but show 100% patency after 1 week, when the animals are treated with coumadines. BES implanted in normal coronary arteries of pigs, which do not receive antithrombotic drugs, are 100% patent after 1 week

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

Real-time volumetric lipid imaging in vivo by intravascular photoacoustics at 20 frames per second

Lipid deposition can be assessed with combined intravascular photoacoustic/ultrasound (IVPA/US) imaging. To date, the clinical translation of IVPA/US imaging has been stalled by a low imaging speed and catheter complexity. In this paper, we demonstrate imaging of lipid targets in swine coronary arteries in vivo, at a clinically useful frame rate of 20 s−1. We confirmed image contrast for atherosclerotic plaque in human samples ex vivo. The system is on a mobile platform and provides real-time data visualization during acquisition. We achieved an IVPA signal-to-noise ratio of 20 dB. These data show that clinical translation of IVPA is possible in principle

In vitro induction of NETosis: Comprehensive live imaging comparison and systematic review

__Background__ Multiple inducers of in vitro Neutrophil Extracellular Trap (NET) formation (NETosis) have been described. Since there is much variation in study design and results, our aim was to create a systematic review of NETosis inducers and perform a standardized in vitro study of NETosis inducers important in (cardiac) wound healing. __Methods__ In vitro NETosis was studied by incubating neutrophils with PMA, living and dead bacteria (S. aureus and E. coli), LPS, (activated) platelets (supernatant), glucose and calcium ionophore Ionomycin using 3-hour periods of time-lapse confocal imaging. __Results__ PMA is a consistent and potent inducer of NETosis. Ionomycin also consistently resulted in extrusion of DNA, albeit with a process that differs from the NETosis process induced by PMA. In our standardized experiments, living bacteria were also potent inducers of NETosis, but dead bacteria, LPS, (activated) platelets (supernatant) and glucose did not induce NETosis. __Conclusion__ Our systematic review confirms that there is much variation in study design and results of NETosis induction. Our experimental results confirm that under standardized conditions, PMA, living bacteria and Ionomycin all strongly induce NETosis, but real-time confocal imaging reveal different courses of events

In-vitro and in-vivo imaging of coronary artery stents with Heartbeat OCT

To quantify the impact of cardiac motion on stent length measurements with Optical Coherence Tomography (OCT) and to demonstrate in vivo OCT imaging of implanted stents, without motion artefacts. The study consists of: clinical data evaluation, simulations and in vivo tests. A comparison between OCT-measured and nominal stent lengths in 101 clinically acquired pullbacks was carried out, followed by a simulation of the effect of cardiac motion on stent length measurements, experimentally and computationally. Both a commercial system and a custom OCT, capable of completing a pullback between two consecutive ventricular contractions, were employed. A 13 mm long stent was implanted in the left anterior descending branch of two atherosclerotic swine and imaged with both OCT systems. The analysis of the clinical OCT images yielded an average difference of 1.1 ± 1.6 mm, with a maximum difference of 7.8 mm and the simulations replicated the statistics observed in clinical data. Imaging with the custom OCT, yielded an RMS error of 0.14 mm at 60 BPM with the start of the acquisition synchronized to the cardiac cycle. In vivo imaging with conventional OCT yielded a deviation of 1.2 mm, relative to the length measured on ex-vivo micro-CT, while the length measured in the pullback acquired by the custom OCT differed by 0.20 mm. We demonstrated motion artefact-free OCT-imaging of implanted stents, using ECG triggering and a rapid pullback