nitinol and Neointima

Self-expanding nitinol stents must be oversized at least by a minimal amount to ensure contact with the vessel wall and prevent migration. Once the stent is deployed it exerts a continuous force upon the vascular wall, termed chronic outward force (COF). Animal studies have found an increased neointimal hyperplasia in stents with high oversizing and thus high COF. Data about correlation between COF and neointimal hyperplasia in humans are currently lacking. The objective of the BIOFLEX-COF trial is to prospectively investigate differences in formation of intimal hyperplasia at 1 and 2 years after implantation of nitinol stents with high versus low COF in de novo femoropopliteal occlusive arterial lesions.. The BIOFLEX-COF trial is a prospective, quantitative, randomized study. Eighty subjects with symptomatic peripheral arterial lesions eligible for endovascular stent implantation will be enrolled and randomly assigned to either a high COF group (LifeStent Flexstar, Bard Peripheral Vascular Inc., Tempe, AZ, USA) or low COF group (Pulsar, Biotronik AG, Bülach, Switzerland) using an online randomization program to generate a random 1:1 group allocation (block randomization). After implantation and dilatation, COF at every 2 mm along the stent axis will be calculated from the actual stent diameter versus its nominal diameter. There will be two follow-up evaluations at 12 and 24 months. Primary endpoint is the amount of in-stent neointima at 1 year, assessed by contrast-enhanced CT angiography (CTA). In the control examinations, stent diameter and true lumen diameter will be measured on DICOM images every 2 mm along the stent axis to quantify the relative amount of in-stent restenosis. Secondary objectives are the amount of in-stent neointima at 2 years, device- and procedure-related adverse events and target lesion revascularization (TLR) rate. The scheduled time for recruitment is 2 years. Recruitment is expected to be complete in October 2017.. This trial is the first to prospectively investigate the influence of COF on stent patency. If successful, the results will aid in a more precise selection of stent type and size in a given target vessel. The present study is challenging in that it compares two different self-expanding nitinol stents head-to-head against each other. To optimize the power of this study, traditional binary outcome parameters such as TLR and restenosis at Doppler ultrasound were dropped as primary endpoints. Instead, the amount of neointima inside the stent accessed by CTA was selected as (continuous) outcome parameter.. ClinicalTrials.gov Identifier: NCT03097679 . Date of registration: 14 March 2017 (retrospectively registered).

Topics: Alloys; Austria; Clinical Protocols; Computed Tomography Angiography; Constriction, Pathologic; Endovascular Procedures; Femoral Artery; Humans; Neointima; Peripheral Arterial Disease; Popliteal Artery; Pressure; Prospective Studies; Prosthesis Design; Recurrence; Research Design; Self Expandable Metallic Stents; Time Factors; Treatment Outcome; Vascular Patency

The aim of this study was to evaluate the Sparrow sirolimus-eluting stent (Sparrow-SES) against the Sparrow bare-metal stent (Sparrow-BMS) and conventional balloon-expandable bare-metal stent (BMS: Driver/Micro-Driver stent, Medtronic Vascular, Santa Rosa, CA).. The Sparrow stent (Biosensors International, Singapore) consists of a guide wire-based, self-expandable, ultra-thin nitinol stent. The performance of this device with sirolimus in a fully biodegradable polymer has not been determined.. A total of 74 patients were included in this intravascular ultrasound (IVUS) sub-study of the CARE II trial, which was a prospective, randomized, multicenter trial in the treatment of single de novo native coronary artery lesions in vessels ranging from 2.0 mm to 2.75 mm in diameter (Sparrow-SES: n = 31, Sparrow-BMS: n = 22, BMS: n = 21).. Stent volume index (VI) was significantly increased 8-month later in Sparrow-SES and Sparrow-BMS, but not in BMS (4.0 ± 1.0 to 4.6 ± 1.0 mm(3) /mm, p<0.0001, 4.0 ± 0.6 to 4.4 ± 0.8 mm(3) /mm, p<0.05, and 5.2 ± 1.0 to 5.1 ± 0.9 mm(3) /mm, p=0.421, respectively). % neointimal obstruction in Sparrow-SES was significantly smaller than those in Sparrow-BMS and BMS at follow-up (17.6 ± 9.4 vs. 36.2 ± 13.8 and 39.9 ± 11.1%, p<0.001). Sparrow-SES showed a mean 15% stent expansion and good suppression of neointimal proliferation, resulting in a significantly lower percentage of change in lumen VI during follow-up period (Sparrow-SES: -6.2 ± 16.2%, Sparrow-BMS: -30.4 ± 11.6%, BMS: -40.4 ± 10.0%, p<0.001).. The self-expanding Sparrow-SES demonstrated chronic stent expansion, good suppression of neointimal proliferation and resulted in a more preserved lumen in stented small vessels compared with the Sparrow-BMS and conventional balloon expandable BMS.

Topics: Aged; Alloys; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The Cappella Sideguard (CS) sidebranch stent is a self-expanding, thin-strut, nitinol device with anatomic flaring at the sidebranch ostium designed to treat bifurcation lesions.. To evaluate the mechanism of long-term lumen patency of the novel, self-expanding CS sidebranch stent compared with a balloon-expandable stent in the main vessel.. We performed intravascular ultrasound postintervention and at follow-up in 24 CS stents and in 28 balloon-expandable drug-eluting stents deployed in the corresponding main vessel. Thirteen patients also had optical coherence tomography (OCT) at follow-up to evaluate neointimal hyperplasia and strut coverage.. CS stent area at the sidebranch carina increased significantly from 3.8 ± 1.2 mm(2) postintervention to 4.6 ± 1.2 mm(2) at follow-up (P < 0.001), resulting in no change in lumen area (3.8 ± 1.2 mm(2) to 3.7 ± 1.2 mm(2) , P = 0.72) despite a neointimal area at follow-up of 0.9 ± 0.8 mm(2) . Volumetric changes were similar, and the distribution of neointimal hyperplasia peaked 1-2 mm distal to the carina. Change of lumen volume inversely correlated to the neointimal volume (R = -0.48, P < 0.001), but correlated positively to the change in stent volume (R = 0.52, P < 0.0001). By OCT, most CS struts were covered (100% [98.9, 100]) at the bifurcation site, whereas 61% of floating DES struts that crossed the sidebranch were covered by smooth tissue with a similar texture compared with neointima.. Although neointimal hyperplasia accumulates within the CS stent mainly 1-2 mm distal to the carina, the self-expanding CS stent may be effective in maintaining an adequate patency in the sidebranch by continued stent expansion noted at follow-up.

Topics: Aged; Alloys; Analysis of Variance; Angioplasty, Balloon, Coronary; Chi-Square Distribution; Coronary Angiography; Coronary Stenosis; Drug-Eluting Stents; Equipment Design; Female; Follow-Up Studies; Humans; Male; Middle Aged; Monitoring, Physiologic; Neointima; Pliability; Prospective Studies; Prosthesis Design; Statistics, Nonparametric; Tomography, Optical Coherence; Ultrasonography, Interventional; Vascular Patency

Restenosis after percutaneous transluminal angioplasty (PTA) of the superficial femoral artery (SFA) may occur in 45% of patients at 2 years follow-up. Paclitaxel-coated balloons have been found to reduce neointimal hyperplasia, and thus reduce restenosis. Recently, the Legflow(®) paclitaxel-coated balloon (Cardionovum Sp.z.o.o., Warsaw, Poland) (LPEB) has been introduced. This balloon is covered with shellac, a Food and Drug Administration (FDA) approved natural resin, to obtain an equally distributed tissue concentration of paclitaxel. The RAPID trial is designed to assess restenosis after PTA using the Legflow balloon combined with nitinol stenting versus uncoated balloons with nitinol stenting in SFA lesions >5 cm.. A total of 176 adult patients with Rutherford class 2 to class 6 symptoms due to intermediate (5-15 cm) or long (>15 cm) atherosclerotic lesions in the SFA will be randomly allocated for treatment with LPEB with nitinol stenting or uncoated balloon angioplasty with stenting. Stenting will be performed using the Supera(®) stent in both groups (IDEV Technologies Inc., Webster, TX). The primary endpoint is the absence of binary restenosis of the treated SFA segment. Secondary outcomes are target lesion revascularization (TLR), clinical and hemodynamic outcome, amputation rate, mortality rate, adverse events, and device-specific adverse events. Follow up consists of four visits in which ankle-brachial indices (ABI), toe pressure measurements, and duplex ultrasound (DUS) will be performed. Furthermore, a peripheral artery questionnaire (PAQ) will be completed by the patients at each follow-up. In the event that DUS reveals a symptomatic >50% restenosis, or a >75% asymptomatic restenosis, additional digital subtraction angiography will be performed with any necessary re-intervention.. The RAPID trial is a multicenter randomized controlled patient blind trial that will provide evidence concerning whether the use of the Legflow paclitaxel/shellac coated balloons with nitinol stenting significantly reduces the frequency of restenosis in intermediate and long SFA lesions compared to standard PTA and stenting.. ISRCTN47846578.

Topics: Alloys; Amputation, Surgical; Angiography, Digital Subtraction; Angioplasty, Balloon; Ankle Brachial Index; Arterial Occlusive Diseases; Cardiovascular Agents; Clinical Protocols; Coated Materials, Biocompatible; Constriction, Pathologic; Equipment Design; Equipment Failure; Femoral Artery; Hemodynamics; Humans; Hyperplasia; Limb Salvage; Neointima; Netherlands; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Prosthesis Failure; Recurrence; Research Design; Resins, Plant; Single-Blind Method; Stents; Surveys and Questionnaires; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Access Devices

The impact of stent design on venous patency is not well studied. The purpose of this study was to investigate the effect of stent material burden on endothelial coverage of stented venous segments, which may contribute to vessel healing and patency.. Segmented self expanding bare nitinol stents (18 × 50 mm) comprising 5 mm long attached metallic rings separated by 2, 5, or 8 mm gaps were implanted in the inferior vena cava (IVC) of 10 sheep. These stents were designed and manufactured for the purposes of this study. At six, 12, and 24 weeks after implantation the animals were euthanised and the stented vessels harvested for histomorphometric analysis. Three sections from the metallic part as well as the gaps between the struts were reviewed for quantification of endothelialisation after six, 12, and 24 weeks. The intimal thickness over and between the stent struts was measured. The endothelialisation score (graded from 1 for complete luminal endothelialisation to 5 for absence of endothelial cells) was determined.. All stents were successfully deployed and all 10 sheep survived until the time of harvesting. Macroscopic inspection after 24 weeks showed only partial endothelialisation over stents with 2 mm and 5 mm skipped segments, whereas the stents with 8 mm skipped segments were totally incorporated into the vein wall. After 24 weeks, the mean (SD) neointimal thicknesses over stent struts with 2 mm, 5 mm, and 8 mm skipped segments were 254.0 (51.6), 182.2 (98.1), and 194.6 (101.1) μm, respectively. Comparison of endothelialisation scores of stents over time showed statistically significantly better endothelialisation over stents with 8 mm gaps after 12 and 24 weeks.. Stent designs providing structural support to veins with larger gaps between the scaffold material appear to lead to faster and more complete endothelialisation as well as a thinner intimal layer.

Topics: Alloys; Animals; Endothelium; Microscopy, Electron, Scanning; Neointima; Prosthesis Design; Random Allocation; Sheep; Stents; Vena Cava, Inferior

Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA.. In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis.. COF is an important cause of restenosis in the distal portion of the SFA stent. Optimal sizing of the SFA stent is important to reduce the incidence of restenosis. Therefore, COF was an important factor of restenosis following distal SFA stenting.

Topics: Alloys; Angioplasty; Animals; Constriction, Pathologic; Female; Femoral Artery; Hemodynamics; Humans; Models, Animal; Neointima; Peripheral Arterial Disease; Prosthesis Design; Prosthesis Failure; Recurrence; Registries; Retrospective Studies; Risk Factors; Self Expandable Metallic Stents; Stress, Mechanical; Sus scrofa; Time Factors; Treatment Outcome

Zilver PTX nitinol self-expanding drug-eluting stent with paclitaxel coating is effective for treatment of superficial femoral artery (SFA) disease. However, as with any stent, it induces a measure of vascular inflammatory response. The current clinical trial (NCT02734836) aimed to assess vascular patency, remodeling, and inflammatory markers with intravascular optical coherence tomography (OCT) in patients with SFA disease treated with Zilver PTX stents.. Serial OCT examinations were performed in 13 patients at baseline and 12-month follow-up. Variables evaluated included neointimal area, luminal narrowing, thrombus area, stent expansion as well as measures of inflammation including, peri-strut low-intensity area (PLIA), macrophage arc, neovascularization, stent strut apposition and coverage.. Percentage of malapposed struts decreased from 10.3 ± 7.9% post-intervention to 1.1 ± 2.2% at 12-month follow-up, but one patient showed late-acquired stent malapposition (LASM). The percent of uncovered struts at follow-up was 3.0 ± 4.5%. Average expansion of stent cross-sectional area from baseline to follow-up was 35 ± 19%. The average neointimal area was 7.8 ± 3.8 mm. At 12-month follow-up, OCT analysis of Zilver PTX stent shows outward remodeling and minimal neointimal growth, but evidence of inflammation including PLIA, neovessels, thrombus and macrophages.. Thirteen patients with PAD had paclitaxel-coated stents implanted in their SFAs and were then imaged with OCT at baseline and 12-month follow-up. OCT proxy metrics of inflammation were quantified.

Topics: Aged; Aged, 80 and over; Alloys; Angioplasty, Balloon; Cardiovascular Agents; Drug-Eluting Stents; Female; Femoral Artery; Humans; Inflammation; Male; Middle Aged; Neointima; Paclitaxel; Peripheral Arterial Disease; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Self Expandable Metallic Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Patency; Vascular Remodeling

Topics: Aged; Alloys; Angioscopy; Antineoplastic Agents; Endovascular Procedures; Femoral Artery; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Neointima; Peripheral Arterial Disease; Predictive Value of Tests; Protein Kinase Inhibitors; Pyrimidines; Stents; Time Factors; Treatment Outcome; Wound Healing

The aim of this study was to elucidate the vascular responses to paclitaxel-eluting stent (Zilver PTX stent) in superficial femoral artery lesion at different elapsed times using angioscopy. Patients who received Zilver PTX stent implantation from five centers were enrolled. We performed angioscopic examinations at 2, 6, and 12 months after implantation and evaluated neointimal coverage (NIC) grade, intra-stent thrombus (IS-Th) grade, and presence of yellow plaque. NIC grade 0 was defined as stent struts exposed; grade 1, struts transparently visible although covered; grade 2, struts embedded in the neointima, but translucent; and grade 3, struts fully embedded and invisible. IS-Th was graded as follows: grade 0 (none), 1 (focal), and 2 (diffusely spread). Angioscopic follow-up evaluation was performed at 2 months (25 patients, 42 lesions), 6 months (18 patients, 23 stents), and 12 months (14 patients, 24 stents) after stent implantation. Dominant NIC grade significantly increased over time; however, 16.3% of the cases had NIC grade 1 or 2 at 12 months. IS-Th grade decreased; however IS-Th and yellow plaque were persistently observed in 62.5% and 83.3% cases, respectively, at 12 months. An ongoing healing response was observed at 12 months after implantation; however, thrombogenic findings were noted. Prolonged dual antiplatelet therapy could potentially enhance the clinical utility of Zilver PTX.

Topics: Aged; Aged, 80 and over; Alloys; Angioscopy; Cardiovascular Agents; Cell Proliferation; Drug-Eluting Stents; Endovascular Procedures; Female; Femoral Artery; Humans; Japan; Male; Middle Aged; Neointima; Paclitaxel; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Self Expandable Metallic Stents; Time Factors; Treatment Outcome; Wound Healing

The study aimed to assess drug adherence, transfer to the vessel wall, tolerance and efficacy of a constrained angioplasty balloon coated with an excipient-enhanced paclitaxel coating (Chocolate coated balloon [CCB]) in the porcine model.. Drug adherence was investigated in vitro. Drug transfer was evaluated in porcine arteries. A stent overstretch model was chosen to provoke intimal thickening in the efficacy and tolerance study. Conventional uncoated balloons were used as controls. CCB were coated with a nominal (3 µg/mm2) and high dose (two completely overlapping inflations each at 6 µg/mm2) of paclitaxel. Efficacy was assessed by histomorphometry and quantitative coronary angiography (QCA). Tolerance, including potential downstream effects, was assessed by myocardial function and histopathology. The CCB lost 6±12% of dose during in vitro simulated delivery to the lesion; drug transfer to the vessel wall was 14±4%. QCA and histomorphometry revealed no baseline differences between treatment groups. Thirty days after treatment, both doses of the CCB resulted in a 50% reduction in neointimal thickening of arteries relative to the uncoated balloon group. Maximum neointimal thickness was 1.12±0.36 mm for uncoated control specimens and 0.46±0.06 mm and 0.44±0.30 mm for the two CCB doses (3 and 2×6 µg/mm2), respectively. There were no device-related animal deaths or changes in left ventricular ejection fraction or device-specific myocardial histopathologies. There were no statistically significant differences between inflammatory scores among treatment groups.. The results demonstrate efficacy and tolerance of a mechanically unique constrained angioplasty balloon within the tested dose range of the selected paclitaxel coating in the chosen porcine preclinical model.

Topics: Alloys; Angioplasty, Balloon, Coronary; Animals; Antineoplastic Agents, Phytogenic; Male; Neointima; Paclitaxel; Swine

This study aimed to assess chronic-phase suppression of neointimal proliferation and arterial healing following paclitaxel-coated (PTX) and bare metal stent (BMS) implantation in the superficial femoral artery using optical coherence tomography (OCT).. Twenty-five patients with 68 stents underwent an 8-month OCT follow-up. Besides standard OCT variables, neointimal characterization and frequencies of peri-strut low-intensity area (PLIA), macrophage accumulation, and in-stent thrombi were evaluated.. The mean neointimal thickness was significantly less with PTX stents (544.9±202.2 μm vs. 865.0±230.6 μm, p<0.0001). The covered and uncovered strut frequencies were significantly smaller and larger, respectively, in the PTX stent group vs. the BMS group (93.7% vs. 99.4%; p<0.0001, 4.0% vs. 0.4%; p<0.0001, respectively). Heterogeneous neointima was only observed in the PTX stent group (12.5% vs. 0%, p=0.017). The frequencies of PLIA and macrophage accumulation were significantly greater in the PTX stent group (87.2% vs. 67.6%, p=0.001 and 46% vs. 9.1%, p=0.003, respectively).. After 8 months, reduced neointimal proliferation was observed with PTX stent implantation. On the other hand, delayed arterial healing was observed compared with BMS.

Topics: Aged; Alloys; Female; Femoral Artery; Humans; Macrophages; Male; Neointima; Paclitaxel; Retrospective Studies; Stents; Tomography, Optical Coherence; Wound Healing

Our aim was to evaluate arterial responses to paclitaxel and a novel fluorocopolymer-coated nitinol low-dose paclitaxel-eluting stent (FP-PES).. Human smooth muscle cell (SMC) migration was assessed after exposure to paclitaxel in vitro. For pharmacokinetics and vascular response, FP-PES or bare metal stents (BMS) were implanted in porcine iliofemoral arteries. Paclitaxel significantly inhibited human coronary and femoral artery SMC migration at doses as low as 1 pM. Inhibition was significantly greater for femoral compared with coronary artery SMCs from 1 pM to 1 μM. Pharmacokinetics showed consistent paclitaxel release from FP-PES over the study duration. The peak arterial wall paclitaxel level was 3.7 ng/mg at 10 days, with levels decreasing to 50% of peak at 60 days and 10% at 180 days. Paclitaxel was not detected in blood or remote organs. Arteriogram and histomorphometry analyses showed FP-PES significantly inhibits neointimal proliferation versus BMS at 30 and 90 days. Re-endothelialisation scores were not different between groups.. Paclitaxel affected femoral artery SMC migration at lower concentrations and to a greater degree than it did coronary artery SMCs. The novel FP-PES used in this preclinical study demonstrated a vascular healing response similar to BMS, while significantly inhibiting neointimal formation up to 90 days.

Topics: Alloys; Animals; Antineoplastic Agents, Phytogenic; Cell Movement; Coronary Vessels; Drug-Eluting Stents; Femoral Artery; Humans; Models, Animal; Myocytes, Smooth Muscle; Neointima; Paclitaxel; Polymers; Swine

This study sought to investigate differences in vascular response between self-expanding bare metal nitinol stents (BMS) and paclitaxel-eluting nitinol stents (PES), in superficial femoral artery (SFA) disease, using optical frequency domain imaging (OFDI).. Six months after stent implantation, follow-up quantitative vascular angiography (QVA) and OFDI assessment were scheduled to evaluate vascular response. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was OFDI-derived late lumen area loss, defined as lumen VI post stent implantation minus lumen VI at follow-up. A total of 28 SFA lesions were analysed, with cases randomised to receive either BMS or PES implantation. QVA-derived diameter stenosis at six-month follow-up was lower in the PES group than in the BMS group (28.5% vs. 39.7%, p=0.04). After six months, BMS VI increased by 33.8% (20.7±3.7 to 27.7±3.5 mm3/mm), whilst PES exhibited an increase of 32.1% (19.0±2.3 to 25.1±4.7 mm3/mm). Neointimal VI was smaller (7.4±2.6 mm3/mm vs. 10.5±3.2 mm3/mm, p<0.01) and late lumen area loss was lower (2.9±1.3 mm3/mm vs. 5.6±2.8 mm3/mm, p<0.01) in the PES group.. Serial volumetric OFDI analyses confirmed significantly smaller amounts of neointimal tissue and lower late lumen area loss following PES implantation for SFA lesions at short-term follow-up.

Topics: Adult; Aged; Aged, 80 and over; Alloys; Drug-Eluting Stents; Female; Femoral Artery; Humans; Male; Middle Aged; Neointima; Optical Imaging; Paclitaxel; Ultrasonography, Interventional

Stent design may influence the outcomes, suggesting that adverse event rates vary according to free cell area and cell design. Open cell design technology of self-expandable stents, dedicated for carotid revascularisation has better deliverability, although closed cell technology is expected to cause fewer thromboembolic events.. To evaluate the feasibility and vascular response of novel, hybrid cell, self-expandable nitinol stents (MER®, Balton, Poland) implanted into porcine carotid arteries. Hybrid cell design combines open and closed cell technology.. All tested stents were implanted with 10% overstretch into 10 carotid segments of Polish domestic pigs. Control angiography was obtained immediately before and after vascular interventions as well as 28 days after the procedure. Thereafter, animals were sacrificed, and the treated segments were harvested and evaluated in the independent histopathology laboratory.. All stents were easily introduced and implanted, showing good angiographic acute outcome. At 28 days, in the angiography, all vessels were patent with no signs of thrombi or excessive neointimal formation, with the late lumen loss of -0.11 ± 0.3 mm and percentage diameter stenosis 10.18 ± 8.1%. There was a 10% increase in the vessel reference diameter when compared to baseline (4.57 ± 0.5 vs. 4.96 ± 0.3 mm, p < 0.01). In the histopathology, mean area stenosis was 17.4% and mean intimal thickness was 0.20 mm. At histopathology, the mean injury, inflammation, and fibrin scores were low. Endothelialisation was complete in all stents, and neointimal tissue appeared moderately mature as shown by the moderate mean neointimal smooth muscle score. Nonetheless, histopathology shows one stent affected by peri-strut granulomas and one stent affected by marked mineralisation.. The novel Polish self-expandable nitinol carotid stent with hybrid cell technology shows optimal biocompatibility and a vascular healing profile, and therefore may be introduced for first-in-man application.

Topics: Alloys; Angioplasty; Animals; Carotid Arteries; Carotid Stenosis; Hybrid Cells; Hyperplasia; Materials Testing; Models, Animal; Neointima; Patient Safety; Prosthesis Design; Stents; Sus scrofa

This study sought to compare the local tissue response and subsequent volume of intimal hyperplasia (IH) that develops throughout the maturation of an arteriovenous fistula created using continuous/interrupted polypropylene with that of a novel, metal-alloy, penetrating anastomotic clip device.. Forty-six fistulae were created in 23 sheep under a paired design using the nitinol U-Clip (n = 23) in one hind limb and continuous (n = 20) or interrupted (n = 3) polypropylene suture for the other. Animals were killed at 4 (n = 3), 14 (n = 3), 28 (n = 10), 42 (n = 3), and 180 (n = 4) days. Histological sections were evaluated for quantitative histology and immunohistochemistry.. Compared with continuous polypropylene, U-Clip specimens demonstrated less intima-media area per unit length (IMA/L), proliferating cells, and tissue necrosis at all time points (MANOVA, F = 9.8-24.1, all p ≤ .005; observed power >82%). Specifically, values of IMA/L were reduced by 5% (p = .97), 37% (p = .02), 33% (p < .01), 9% (p = .42), and 14% (p = .22) at the time points of 4, 14, 28, 42, and 180 days respectively. Proliferating cells were reduced by 75% (p < .01), 72% (p = .03), 76% (p = .03), 27% (p = .31), and 60% (p = .01) and tissue necrosis by 67% (p < .01), 58% (p = .02), 40% (p = .33), 21% (p = .43), 77% (p = .11). In a 28-day comparison between U-Clip and interrupted polypropylene the U-Clip group demonstrated a 4% (p = .65) reduction in IMA/L, 74% (p < .01) in proliferating cells and 49% (p < .05) in tissue necrosis.. These results provide evidence of reduced local tissue necrosis, proliferating cells, and IH, favouring arteriovenous fistulae created using the U-Clip anastomotic device over conventional polypropylene suture techniques most evident over the first 4 weeks.

Topics: Alloys; Animals; Arteriovenous Shunt, Surgical; Cell Proliferation; Equipment Design; Femoral Artery; Femoral Vein; Hindlimb; Hyperplasia; Models, Animal; Muscle, Skeletal; Necrosis; Neointima; Polypropylenes; Sheep; Surgical Instruments; Suture Techniques; Sutures; Time Factors

To compare the vascular response after paclitaxel-coated nitinol drug-eluting stent (Zilver PTX) implantation for superficial femoral artery lesions after 6 and 12 months using optical coherence tomography (OCT).. Serial OCT examinations were performed in 5 patients (4 men; mean age 78.4 ± 6.8 years) with 9 Zilver PTX stents at 6- and 12-month follow-up. Variables evaluated included neointimal thickness and apposition on each strut, the incidence of extrastent lumen (ESL), peristrut low-intensity area (PLIA), and neovascularization at 1-mm intervals.. A total of 249 matched cross-section images were evaluated and included 4788 and 4826 struts at 6 and 12 months, respectively. Mean neointimal thickness significantly increased from 480 to 540 µm between 6 and 12 months (p < 0.001). The percentage of uncovered struts tended to decrease at 12 months (3% vs. 2.3%, p = 0.054), whereas the percentage of malapposed struts were similar at both examinations (0.2% vs. 0.2%, p > 0.99). Although the incidence of ESL in cross sections was not different (35% vs. 31%, p = 0.29), median ESL area significantly increased from 6 to 12 months [0.12 (0.04-0.36) vs. 0.31 (0.14-0.59) mm(2), p = 0.003)]. The presence of PLIA (29% vs. 44%, p < 0.001) and neovascularization (14% vs. 27%, p < 0.001) increased from 6 to 12 months.. These findings suggest that delayed vascular healing and persistent peristent inflammation may be present even at 12 months after Zilver PTX implantation.

Topics: Aged; Aged, 80 and over; Alloys; Cardiovascular Agents; Drug-Eluting Stents; Female; Femoral Artery; Follow-Up Studies; Humans; Male; Neointima; Paclitaxel; Peripheral Arterial Disease; Predictive Value of Tests; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Tomography, Optical Coherence; Treatment Outcome

Different flow patterns and shear forces were shown to cause significantly more luminal narrowing and neointimal tissue proliferation in coronary than in infrainguinal vein grafts. As constrictive external mesh support of vein grafts led to the complete suppression of intimal hyperplasia (IH) in infrainguinal grafts, we investigated whether mesh constriction is equally effective in the coronary position.. Eighteen senescent Chacma baboons (28.8 ± 3.6 kg) received aorto-coronary bypass grafts to the left anterior descending artery (LAD). Three groups of saphenous vein grafts were compared: untreated controls (CO); fibrin sealant-sprayed controls (CO + FS) and nitinol mesh-constricted grafts (ME + FS). Meshes consisted of pulse-compliant, knitted nitinol (eight needles; 50 μm wire thickness; 3.4 mm resting inner diameter, ID) spray attached to the vein grafts with FS. After 180 days of implantation, luminal dimensions and IH were analysed using post-explant angiography and macroscopic and histological image analysis.. At implantation, the calibre mismatch between control grafts and the LAD expressed as cross-sectional quotient (Qc) was pronounced [Qc = 0.21 ± 0.07 (CO) and 0.18 ± 0.05 (CO + FS)]. Mesh constriction resulted in a 29 ± 7% reduction of the outer diameter of the vein grafts from 5.23 ± 0.51 to 3.68 ± 0 mm, significantly reducing the calibre discrepancy to a Qc of 0.41 ± 0.17 (P < 0.02). After 6 months of implantation, explant angiography showed distinct luminal irregularities in control grafts (ID difference between widest and narrowest segment 74 ± 45%), while diameter variations were mild in mesh-constricted grafts. In all control grafts, thick neointimal tissue was present [600 ± 63 μm (CO); 627 ± 204 μm (CO + FS)] as opposed to thin, eccentric layers of 249 ± 83 μm in mesh-constricted grafts (ME + FS; P < 0.002). The total wall thickness had increased by 363 ± 39% (P < 0.00001) in CO and 312 ± 61% (P < 0.00001) in CO + FS vs 82 ± 61% in ME + FS (P < 0.007).. In a senescent non-human primate model for coronary artery bypass grafts, constrictive, external mesh support of saphenous veins with knitted nitinol prevented focal, irregular graft narrowing and suppressed neointimal tissue proliferation by a factor of 2.5. The lower degree of suppression of IH compared with previous infrainguinal grafts coincided with a lesser reduction of calibre mismatch in the coronary grafts.

Topics: Alloys; Animals; Blood Vessel Prosthesis; Coronary Angiography; Coronary Artery Bypass; Coronary Vessels; Histology; Neointima; Papio; Statistics, Nonparametric

We investigated tissue responses to endoskeleton stent grafts for saccular abdominal aortic aneurysms (AAAs) in canines. Saccular AAAs were made with Dacron patch in 8 dogs, and were excluded by endoskeleton stent grafts composed of nitinol stent and expanded polytetrafluoroethylene graft. Animals were sacrificed at 2 months (Group 1; n = 3) or 6 months (Group 2; n = 5) after the placement, respectively. The aortas embedding stent grafts were excised en bloc for gross inspection and sliced at 5 to 8 mm intervals for histopathologic evaluation. Stent grafts were patent in all except a dog showing a thrombotic occlusion in Group 2. In the 7 dogs with patent lumen, the graft overhanging the saccular aneurysm was covered by thick or thin thrombi with no endothelial layer, and the graft over the aortic wall was completely covered by neointima with an endothelial layer. Transgraft cell migration was less active at an aneurysm than at adjacent normal aorta. In conclusion, endoskeleton stent grafts over saccular aneurysms show no endothelial coverage and poor transgraft cell migration in a canine model.

Topics: Alloys; Angiography; Animals; Aortic Aneurysm, Abdominal; Cell Movement; Disease Models, Animal; Dogs; Endothelial Cells; Neointima; Polytetrafluoroethylene; Stents; Thrombosis; Tomography, X-Ray Computed; Ultrasonography

Neointimal hyperplasia is a major complication of endovascular stent placement with consequent in-stent restenosis or occlusion. Improvements in the biocompatibility of stent designs could reduce stent-associated thrombosis and in-stent restenosis. We hypothesised that the use of a diamond-like carbon (DLC)-coated nitinol stent or a polyethylene glycol (PEG)-DLC-coated nitinol stent could reduce the formation of neointimal hyperplasia, thereby improving stent patency with improved biocompatibility.. A total of 24 stents were implanted, under general anaesthesia, into the iliac arteries of six dogs (four stents in each dog) using the carotid artery approach. The experimental study dogs were divided into three groups: the uncoated nitinol stent group (n = 8), the DLC-nitinol stent group (n = 8) and the PEG-DLC-nitinol stent group (n = 8).. The mean percentage of neointimal hyperplasia was significantly less in the DLC-nitinol stent group (26.7±7.6%) than in the nitinol stent group (40.0±20.3%) (p = 0.021). However, the mean percentage of neointimal hyperplasia was significantly greater in the PEG-DLC-nitinol stent group (58.7±24.7%) than in the nitinol stent group (40.0±20.3%) (p = 0.01).. Our findings indicate that DLC-coated nitinol stents might induce less neointimal hyperplasia than conventional nitinol stents following implantation in a canine iliac artery model; however, the DLC-coated nitinol stent surface when reformed with PEG induces more neointimal hyperplasia than either a conventional or DLC-coated nitinol stent.

Topics: Alloys; Animals; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Dogs; Hyperplasia; Iliac Artery; Neointima; Polyethylene Glycols; Stents

To evaluate the feasibility of using covered stents vs. bare stents in a model of central vein stenosis with an arteriovenous graft created to mimic the conditions in hemodialysis patients.. In 7 mongrel dogs, an expanded polytetrafluoroethylene-covered nitinol stent was placed in one common iliac vein and a bare stent was placed in the contralateral vein. Arteriovenous grafts were created bilaterally between the common femoral artery and vein to induce endothelial damage. Neointima formation in the covered stents was compared to the bare stents at 12 weeks using microscopy and histochemical staining.. Two dogs were excluded due to thrombosis and infection of the arteriovenous grafts, but all stents in the remaining 5 dogs were patent. Smooth, complete neointimal coverage was observed on the inner surface of all the covered stents without intraluminal thrombus. In contrast, incomplete neointimal coverage was seen in all bare stents, with small focal thrombi adhering to the neointima on 3 bare stents. Focal nodular neointimal hyperplasia with denudation of the endothelium was observed in only 2 bare stents. Mean neointimal thickening was significantly greater in the covered stents. Eccentric neointimal thickening was observed at the inflow and outflow segments of both types of stents.. Covered stents are technically feasible for the treatment of central vein stenosis, and they demonstrate complete, smooth neointimal coverage in normal central veins, but they also display greater neointimal thickening than bare stents.

Topics: Alloys; Animals; Arteriovenous Anastomosis; Blood Vessel Prosthesis; Constriction, Pathologic; Disease Models, Animal; Dogs; Feasibility Studies; Femoral Artery; Iliac Vein; Neointima; Polytetrafluoroethylene; Prosthesis Design; Renal Dialysis; Stents