Endovascular stroke therapy: tirofiban is associated with risk of fatal intracerebral hemorrhage and poor outcome.

BACKGROUND AND PURPOSE: To investigate the relationship between severe bleeding complications and outcome after mechanical thrombectomy with or without glycoprotein-IIb/IIIa inhibitor tirofiban treatment. METHODS: The study included prospectively collected data of consecutive patients with acute ischemic stroke in whom mechanical thrombectomy was perfomed in the years 2006 to 2011. RESULTS: Of 162 patients, 128 patients had anterior circulation stroke, and 34 patients had posterior circulation stroke. Additional treatment with tirofiban was given to 30 of 128 patients with anterior circulation stroke and to 20 of 34 patients with posterior circulation stroke. Treatment with tirofiban did not influence recanalization rates. Fatal intracerebral hemorrhage occurred more frequently in tirofiban-treated patients in the entire cohort (12.0% vs 2.7%; P=0.03) and in tirofiban-treated patients with anterior circulation stroke (13.3% vs 3.1%; P=0.05). Logistic regression found age (odds ratio, 1.17; 95% confidence interval, 1.00-1.37; P=0.05) and tirofiban treatment (odds ratio, 3.03; 95% confidence interval, 1.50-4.05; P=0.04) to be independent predictors for fatal intracerebral hemorrhage. Tirofiban treatment was also an independent predictor for poor outcome (odds ratio, 6.60; 95% confidence interval, 1.06-41.52; P=0.04) in addition to National Institute of Health Stroke Scale (odds ratio, 1.08; 95% confidence interval, 1.00-1.17; P=0.05). CONCLUSIONS: In endovascular stroke therapy, additional treatment with the glycoprotein-IIb/IIIa inhibitor tirofiban is associated with increased risk of fatal intracerebral hemorrhage and poor outcome.

Mechanical thrombectomy in acute embolic stroke: preliminary results with the revive device.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the safety and technical feasibility of a new thrombectomy device (Revive; Micrus Endovascular) in the endovascular treatment of acute ischemic stroke. METHODS: Ten patients with acute large vessel occlusions were treated with the Revive device between October 2010 and December 2010. Mean National Institutes of Health Stroke Scale on admission was 19.0; mean duration of symptoms was 172 minutes. Recanalization was assessed using the Thrombolysis In Cerebral Infarction score. Clinical outcome (National Institutes of Health Stroke Scale) after thrombectomy was determined on Day 1, at discharge, and at Day 30. RESULTS: Vessel recanalization (Thrombolysis In Cerebral Infarction 2b or 3) was successful in all patients without device-related complications. Mean National Institutes of Health Stroke Scale 24 hours after the intervention, at discharge, and at Day 30 was 14.0, 11.5, and 5.1, respectively. At Day 30, 6 patients had a clinical improvement of >8 points or an National Institutes of Health Stroke Scale of 0 to 1, 1 patient showed minor improvement, and 3 patients had died. Symptomatic intracranial hemorrhage occurred in 2 patients, of which 1 was fatal. CONCLUSIONS: Thrombectomy with the Revive device in patients with stroke with acute large vessel occlusions demonstrated to be technically safe and highly effective. Clinical safety and efficacy have to be established in larger clinical trials.

Paclitaxel-induced arterial wall toxicity and inflammation: tissue uptake in various dose densities in a minipig model.

PURPOSE: Paclitaxel is an antiproliferative agent in drug-eluting stents with largely unknown tissue interaction. Toxicity might result from overdosage and/or accumulation. Part 1 of this two-step study investigated how paclitaxel uptake depends on dose density, coronary drug transfer kinetics, and elution efficacy. MATERIALS AND METHODS: With cobalt chromium stents and Polyzene-F nanoscale coating, low, intermediate, and high paclitaxel dose densities (25 microg, 50 microg, and 150 microg per stent) were investigated in porcine right coronary arteries (RCAs). Coronary and myocardial tissue concentration measurements and determination of on-stent paclitaxel and plasma concentrations were performed at 2, 8, 24, and 72 hours. RESULTS: For all stents, uptake was similar at all time intervals (paclitaxel RCA concentration range, 1,610-33,300 ng). Low- and intermediate-dose stents showed similar RCA concentrations, but those for high-dose stents were three times greater. Residual on-stent paclitaxel concentration was not time-dependent, at 33.3% on low-, 30.6% on intermediate-, and 17.4% on high-dose stents. Paclitaxel was measurable in only the plasma immediately after stent placement, with a linear dose relationship and a timely regression: measurements in high-dose stents were 0.0454-0.656 ng/mL at 1 minute and 0.0329-0.0879 ng/mL at 5 minutes. Untreated control samples of the left coronary artery showed a linear dose-dependent concentration (12.6 ng/g, 21.2 ng/g, and 85.2 ng/g). CONCLUSIONS: Overall coronary paclitaxel uptake is fairly independent from the baseline overall dose density and, hence, depends on immediate binding mechanisms of the arterial wall. This is supported by the fact that, regardless of the applied dose density, the kinetics of paclitaxel uptake did not follow an exposure time pattern.

Paclitaxel-induced arterial wall toxicity and inflammation: part 2--long-term tissue response in a minipig model.

PURPOSE: In part 1 of the present study, the authors demonstrated that coronary paclitaxel uptake from drug eluting stents (DESs) was not dependent on exposure time and dose. In this second part, the effect of the different paclitaxel dose densities on long-term biologic behavior was evaluated. MATERIALS AND METHODS: In 40 minipigs, (with 4- and 12-week follow-up), identical stents with the same three paclitaxel dose densities as in part 1 were implanted in the right coronary artery. Minipigs implanted with Polyzene-F nanocoated stents served as the control group. Quantitative angiography measuring average luminal diameter (from three in-stent reference points), minimal luminal diameter (from the point of maximum in-stent stenosis), average late loss, maximum late loss, and binary stenosis rate was performed, as was microscopy to determine neointimal thickening, injury score, and inflammation. RESULTS: All three DESs were associated with a high average late loss, binary stenosis rate, and neointimal thickening, without significant differences. Drug-free stents had significantly less late in-stent stenosis: there was an average late loss of 0.3 mm +/- 0.3 in drug-free stents versus 0.8 mm +/- 0.2 in intermediate-dose stents and 1.5 mm +/- 0.6 in high-dose stents (P = .04). DES-associated inflammation was high in all DESs and six times higher as in the drug-free stents (Kornowski scores of 0.2 +/- 0.1 in drug-free stents, 1.3 +/- 0.9 in low-dose stents, 1.7 +/- 0.8 in intermediate-dose stents, and 1.3 +/- 1.0 in high-dose stents; P = .04). It worsened with time in all DESs, as did late in-stent stenosis. CONCLUSIONS: The extensive and long-term retention of paclitaxel even in a low-dose formulation, at least according to the present labeling of DESs, might be associated with negative long-term results with regard to inflammation and late in-stent stenosis.

Arterial distribution characteristics of Embozene particles and comparison with other spherical embolic agents in the porcine acute embolization model.

PURPOSE: To determine the arterial distribution pattern of the embolic agent Embozene within the porcine kidney and compare it with those of other spherical embolic agents. MATERIALS AND METHODS: Embozene, Embosphere, Bead Block, and Contour SE in size classes of 100-300 microm, 500-700 microm, and 700-900 microm and Embozene and Embosphere in the size class of 40-120 microm were used for total arterial occlusion in minipig kidneys. Organs were evaluated microscopically regarding vascular distribution of the different embolic agents and particle sizes. RESULTS: The following variations of arterial distribution were identified. In the 40-120-microm size class, Embosphere particles penetrated significantly deeper compared with Embozene (P = .04). In the 100-300-microm size class, Bead Block showed a significantly deeper distribution as microscopy identified particles in arteries much smaller than their nominal size. In the 500-700-microm size class, Embosphere and Contour SE showed a deeper distribution. The most uniform arterial distribution was observed in the 700-900 microm size class,. However, few Embosphere and Contour SE particles were found in arcuate arteries, also indicating a distal distribution. CONCLUSIONS: Throughout the four most-used size classes, from very small (40-120 microm) to large (700-900 microm), the distribution characteristics of the four tested materials vary substantially. Particularly, small Embosphere particles and small Bead Block particles showed a more distal distribution, as did medium-sized Embosphere and Contour SE particles. In the largest investigated size class, the distribution was more uniform. In general, the Embozene particles are very uniform in size, and they seem to reach vessels closely corresponding to their nominal size.

Immunohistochemical characterization of specific inflammatory tissue reactions following embolization with four different spherical agents in the minipig kidney model.

PURPOSE: To evaluate the immunohistochemical inflammatory reaction after porcine renal embolization with the new spherical embolic agent Embozene and to compare it with other spherical embolic agents. MATERIALS AND METHODS: After superselective porcine renal embolization (40 pigs) with different sizes of embolic agents (Embozene, Embosphere, Bead Block, Contour SE), tissue arrays were obtained (size ranges, 40-120 microm, 100-300 microm, 500-700 microm, 700-900 microm). After immunostaining for CD subtyping (CD45 and CD68) and cytokines (C-reactive protein [CRP] and interleukin-1 beta), a semiquantitative immunoreactivity score was calculated for each marker: intensity of staining was scored between 0 (negative) and 3 (intensive) and extent of staining between 0 and 4 (>80%), indicating the percentage of positive staining. The intensity score (0-3) was multiplied by the extent of staining score (0-4), resulting in a semiquantitative immunoreactivity score (0-12). RESULTS: Analysis of cellular expression profiles (ie, CD45, CD68) revealed a significantly higher inflammatory score 4 weeks after embolization with Embosphere 100-300 microm particles than after embolization with Embozene, Bead Block, and Contour SE. After 12 weeks, the Embosphere 100-300 microm score decreased. Analysis of CRP expression showed similar results, with a significantly higher score 4 weeks after embolization with Embosphere 100-300 microm. In the size class used most frequently for uterine artery emboliation (500-700 microm), all scores were low (<2.5) and there was no significant difference among particle types. CONCLUSIONS: Pronounced immunomarker expression was seen 4 weeks after embolization with small Embosphere particles. However, in general, modern spherical embolic agents cause a fairly low level of inflammatory reaction. In the present experimental setting, which is highly sensitive for specific tissue-to-agent reactivity, Embozene presented with low inflammatory results.

The efficacy of nanoscale poly[bis(trifluoroethoxy) phosphazene] (PTFEP) coatings in reducing thrombogenicity and late in-stent stenosis in a porcine coronary artery model.

OBJECTIVES: Previous experimental studies have demonstrated that poly[bis(trifluoroethoxy)phosphazene] (PTFEP) nanocoated stents have antithrombotic characteristics, reduce in-stent stenosis, prevent wall inflammation, and do not hamper endothelialization. This study was designed to validate these findings in a porcine coronary artery model. MATERIALS AND METHODS: PTFEP-coated (n = 15) and bare stents (n= 13) were implanted in coronary arteries of 18 mini-pigs (4- and 12-week follow-up). Primary study endpoints were thrombogenicity and in-stent stenosis, secondary study endpoints were inflammatory response and re-endothelialization evaluated by quantitative angiography and light microscopy. RESULTS: No thrombus deposition occurred on any stent. At 4 weeks follow-up, the bare stents (n = 4) had a significantly smaller neointimal area (1.93 vs. 3.20 mm(2), P = 0.009). At 12 weeks, PTFEP-coated stents (n = 11) had significantly superior results in almost all parameters: neointimal area (2.25 vs. 2.65 mm(2), P = 0.034), neointimal height (204.46 vs. 299.41 microm, P = 0.048), percentage stenosis (38.25 vs. 50.42%, P = 0.019), and inflammation score (0.12 vs. 0.30, P = 0.029). Complete re-endothelialization was seen in both stent types at both intervals. CONCLUSION: At long-term follow-up, the superior results of PTFEP-coated stents were characterized by a noteworthy reduction of neointimal growth and inflammatory response.

Combined proximal balloon occlusion and distal aspiration: a new approach to prevent distal embolization during neurothrombectomy.

BACKGROUND AND PURPOSE: Embolization of thrombus fragments in a new vascular territory is a potential adverse event in neurothrombectomy. This study was performed to evaluate the safety and feasibility of a novel approach combining proximal balloon occlusion and distal aspiration to prevent distal thrombembolic complications. METHODS: Patients with ischemic stroke meeting the following inclusion criteria were eligible: occlusion in the anterior circulation, neurothrombectomy using a balloon catheter for proximal flow arrest, and an intermediate catheter for distal aspiration. Pre- and post-interventional Thrombolysis In Cerebral Infarction (TICI) scores were assessed. Clinical presentation at admission and discharge and after 3 months was also evaluated and complications (particularly new thrombembolic events) were recorded. RESULTS: We retrospectively identified 31 patients from our prospectively collected stroke database who met the inclusion criteria. In all patients the initial TICI was 0. A TICI score of ≥2b was achieved in 96.8%. No new thrombembolic complications occurred. The median NIH Stroke Scale score was 19 at admission and 4.5 at discharge. After 3 months, 51.6% of the patients had a favorable clinical outcome (modified Rankin Scale score 0-2) and 19.3% had died. CONCLUSIONS: A combination of proximal internal carotid artery occlusion using a balloon catheter and distal aspiration through an intermediate catheter represents a safe and efficient adjunct to mechanical thrombectomy with stent retrievers. In our patient cohort, no new thrombembolic complications were detected.

Initial experience with a new distal intermediate and aspiration catheter in the treatment of acute ischemic stroke: clinical safety and efficacy.

PURPOSE: To describe our initial experience with the novel 5 F SOFIA (Soft Torqueable catheter Optimized For Intracranial Access) intermediate and aspiration catheter for endovascular treatment of patients with acute ischemic stroke. METHODS: A retrospective review was performed in three centers of prospectively collected data of all stroke patients who underwent endovascular therapy using the SOFIA catheter. Patients were enrolled between November 2013 and December 2014. The primary endpoint of the study was accessibility of the thrombus with the SOFIA catheter. As a secondary endpoint, the study assessed recanalization success (Thrombolysis In Cerebral Infarction (TICI) ≥2b). Clinical presentation on admission and discharge was also documented. In addition, catheter- and procedure-related complications (particularly thromboembolic complications) were recorded. RESULTS: The SOFIA catheter was used in 115 acute stroke procedures. In 110 cases (96%) the catheter could be advanced to the occlusion site. After mechanical thrombectomy, successful recanalization (TICI ≥2b) was documented in 86.9%. There were no complications related to positioning of the catheter. Distal thrombus migration into a new vascular territory occurred in three patients following thrombectomy with a stent retriever (2.6%). The mean NIH Stroke Scale (NIHSS) score on admission was 16.8±6 and at discharge the mean NIHSS score was 8.2±7.7. Sixteen patients died. CONCLUSIONS: The SOFIA catheter is a safe and efficient catheter for endovascular stroke therapy.

A new polymer concept for coating of vascular stents using PTFEP (poly(bis(trifluoroethoxy)phosphazene) to reduce thrombogenicity and late in-stent stenosis.

OBJECTIVES: We sought to evaluate the new polymer PTFEP (poly(bis(trifluoroethoxy)phosphazene) for (1) its ability to reduce thrombogenicity and late in-stent stenosis and (2) its effect on endothelialization in a rabbit iliac artery model. MATERIALS AND METHODS: Nanocoated ( approximately 50 nm) and bare stainless-steel stents were implanted bilaterally in the iliac arteries of 30 New Zealand White rabbits (1, 4, 8, 12, and 16 weeks follow-up) and evaluated by angiography, light, and scanning electron microscopy. RESULTS: Bilateral stent placement was successful in 27 of 30 rabbits. Thrombus depositions occurred in none of the 27 coated but in 4 of the 27 bare stents (P=0.037). A normal angiogram was obtained in 18 of 22 coated stents at risk for restenosis (follow-up >or=4 weeks) but only in 13 of 22 bare stents (P=0.023). Marked restenosis (luminal loss >30%) was found in 6 bare stents (P=0.011) but not in any coated stents. The neointima was 47.7-73.9 mum on coated and 66.9-115.2 mum on bare stents (statistically significant at 4, 8, and 16 weeks). Scanning electron microscopy detected full endothelialization in all stents from 4 weeks on (22 stents in both groups). CONCLUSION: PTFEP nanocoating successfully showed thromboresistance and reduced late in-stent stenosis. Endothelialization was equal in both stent types. Studies in more human-like models and human feasibility studies in human arteries are encouraged.

Noninvasive cerebral oximetry during endovascular therapy for acute ischemic stroke: an observational study.

Implementing endovascular stroke care often impedes neurologic assessment in patients who need sedation or general anesthesia. Cerebral near-infrared spectroscopy (NIRS) may help physicians monitor cerebral tissue viability, but data in hyperacute stroke patients receiving endovascular treatment are sparse. In this observational study, the NIRS index regional oxygen saturation (rSO2) was measured noninvasively before, during, and after endovascular therapy via bilateral forehead NIRS optodes. During the study period, 63 patients were monitored with NIRS; 43 qualified for analysis. Before recanalization, 10 distinct rSO2 decreases occurred in 11 patients with respect to time to intubation. During recanalization, two kinds of unilateral rSO2 changes occurred in the affected hemisphere: small peaks throughout the treatment (n=14, 32.6%) and sustained increases immediately after recanalization (n=2, 4.7%). Lower area under the curve 10% below baseline was associated with better reperfusion status (thrombolysis in cerebral infarction ≥ 2b, P=0.009). At the end of the intervention, lower interhemispheric rSO2 difference predicted death within 90 days (P=0.037). After the intervention, higher rSO2 variability predicted poor outcome (modified Rankin scale > 3, P=0.032). Our findings suggest that bi-channel rSO2-NIRS has potential for guiding neuroanesthesia and predicting outcome. To better monitor local revascularization, an improved stroke-specific set-up in future studies is necessary.

Midterm results of uterine artery embolization using narrow-size calibrated embozene microspheres.

PURPOSE: To evaluate safety and efficacy of uterine artery embolization using narrow-size-range polyphosphazene-coated hydrogel microspheres (Embozene, CeloNova Biosciences, Newnan, GA). METHODS: Between May 2006 and September 2008, a total of 121 consecutive patients (mean ± SD age 42.1 ± 5.4 years, range 30.5-51.5 years) were enrolled onto this single-center study. The primary study endpoint was safety as assessed by the society of interventional radiology (SIR) classification. The secondary endpoint was efficacy, which was based on a 1-year magnetic resonance imaging study and relief of symptoms documented by the Medical Outcomes Study 36-Item Short-Form Health Survey questionnaire over a 2-year interval. RESULTS: The mean ± SD diameter of the dominant fibroid was 6.4 ± 2.6 (range, 2.9-13.9) cm and the mean volume 137.2 ± 245.1 (range, 5.3-1184) ml. Most patients had multiple fibroids with 11% more than 10. A total of 240 of 242 interventions were completed as planned, a technical success rate of 99.2%. According to the SIR classification, one type A, eight type C, and one type D complication occurred. Total devascularization was noted in 96% (116 of 121) of dominant fibroids. Volume decrease was 4% at 2 weeks, 52% (P < 0.001) at 3 months, 78% (P < 0.001) at 6 months, and 91% at 12 months (P < 0.001). The latter difference was statistically significant (P = 0.007). A total of 92% had improved hypermenorrhea at 1 year and 94% at 2 years. Dysmenorrhea was improved in 96% at 1 year and in 95% at 2 years. The overall health status score was 60.4 ± 26.2 points at baseline and 96.9 ± 3.8 after 1 year (P = 0.0019). CONCLUSION: Uterine artery embolization with Embozene microspheres is a safe procedure. Its efficacy is demonstrated by high fibroid devascularization and volume reduction rates and significant improvements of clinical symptoms and quality-of-life scores during follow-up.

Experimental liver embolization with four different spherical embolic materials: impact on inflammatory tissue and foreign body reaction.

We sought to describe and compare material specific inflammatory and foreign body reactions after porcine liver embolization with spherical embolic agents. In 40 animals, superselective liver embolization was performed with four different spherical embolic agents of various sizes: 40-120 microm (Embozene, Embosphere), and 100-300 microm, 500-700 microm, and 700-900 microm (Embozene, Embosphere, Bead Block, and Contour SE, respectively). After 4 or 12 weeks, inflammatory reactions were evaluated microscopically according to the Banff 97 classification. For investigation of foreign body reactions, a newly designed giant cell score was applied. Banff 97 and giant cell scores closely correlated. At 4 weeks, small Embosphere particles (100-300 microm) had a significantly higher Banff 97 score than Embozene, Bead Block, and Contour SE of the corresponding size. After 12 weeks, the calculated differences were not statistically significant. Comparison between the 4-week results and the 12-week results revealed a statistically higher Banff 97 score for Embosphere 100-300 microm after 4 weeks than after 12 weeks (P = 0.02). The overall foreign body reaction was pronounced after embolization with smaller particles, especially in small Embosphere particles. Giant cell numbers with Embosphere 100-300 microm were statistically higher compared with the other materials of corresponding size (P < 0.0001). Inflammatory and giant cell reactions after embolization procedures depend on the embolic material. The overall inflammatory reaction was low. However, marked inflammation was associated with small Embosphere particles at 4 weeks, a finding that might be caused by the allogeneic overcoat. Correspondingly, giant cells indicating a foreign body reaction were more frequently associated with small particle sizes, especially after embolization with small Embosphere particles.

Analysis of nontarget embolization mechanisms during embolization and chemoembolization procedures.

Complications of embolization and chemoembolization remain a problem even with the development of low-profile catheter material and the introduction of new embolization agents. In recent years many new embolization materials have become available for clinical use, so the possibilities and limitations of these new materials must be understood to allow safe and effective embolization. Although up to now some scientific work has been published reporting the basic risk of embolization procedures, the underlying pathomechanism remains the object of speculation. Besides complications like drug toxicity, allergic reactions, and bleeding of the puncture site, the characteristics of embolization materials must be known to understand the potential complications of nontarget embolization and reflux of embolization material. This article gives an overview of established and new embolization materials, their potential risks, and the underlying pathophysiology.

Restenosis of the CYPHER-Select, TAXUS-Express, and Polyzene-F nanocoated cobalt-chromium stents in the minipig coronary artery model.

PURPOSE: To date no direct experimental comparison between the CYPHER-Select and TAXUS-Express stents is available. Therefore, we investigated late in-stent stenosis, thrombogenicity, and inflammation, comparing the CYPHER-Select, TAXUS-Express, and custom-made cobalt chromium Polyzene-F nanocoated stents (CCPS) in the minipig coronary artery model. METHODS: The three stent types were implanted in the right coronary artery of 30 minipigs. The primary endpoint was in-stent stenosis assessed by quantitative angiography and microscopy. Secondary endpoints were inflammation and thrombogenicity evaluated by scores for inflammation and immunoreactivity (C-reactive protein and transforming growth factor beta). Follow-up was at 4 and 12 weeks. RESULTS: Stent placement was successful in all animals; no thrombus deposition occurred. Quantitative angiography did not depict statistically significant differences between the three stent types after 4 and 12 weeks. Quantitative microscopy at 4 weeks showed a statistically significant thicker neointima (p = 0.0431) for the CYPHER (105.034 +/- 62.52 microm) versus the TAXUS (74.864 +/- 66.03 microm) and versus the CCPS (63.542 +/- 39.57 microm). At 12 weeks there were no statistically significant differences. Inflammation scores at 4 weeks were significantly lower for the CCPS and CYPHER compared with the TAXUS stent (p = 0.0431). After 12 weeks statistical significance was only found for the CYPHER versus the TAXUS stent (p = 0.0431). The semiquantitative immunoreactivity scores for C-reactive protein and transforming growth factor beta showed no statistically significant differences between the three stent types after 4 and 12 weeks. CONCLUSIONS: The CCPS provided effective control of late in-stent stenosis and thrombogenicity in this porcine model compared with the two drug-eluting stents. Its low inflammation score underscores its noninflammatory potential and might explain its equivalence to the two DES.

Inflammation and recanalization of four different spherical embolization agents in the porcine kidney model.

PURPOSE: To evaluate the pattern of recanalization and specific inflammatory reaction after superselective embolization with four commercially available spherical embolic agents of different sizes in the mini pig kidney model. MATERIALS AND METHODS: In 40 mini pigs, the lower poles of both kidneys were superselectively embolized with Embozene, Embosphere, Bead Block, and Contour SE particles in sizes of 40-120 mircom (Embozene, Embosphere) and 100-300 microm, 500-700 microm, and 700-900 microm (Embozene, Embosphere, Bead Block, Contour SE). After a follow-up time of 4 or 12 weeks, recanalization was determined with angiography. Pathologic and histologic evaluation of the kidneys was performed, and the Banff 97 classification was used to evaluate the extent of vessel wall inflammation. Macroscopically visible ischemic changes were evaluated by using a specific ischemia score. RESULTS: After embolization with Embozene microspheres, larger Embosphere particles, and Bead Block and Contour SE particles, the absence of inflammation or a low inflammation score was observed. Significantly elevated inflammation scores were evident with small Embosphere particles after 4 weeks (mean score, 1.21 +/- 1.0). Distinct recanalization occurred with Contour SE particles (100% recanalization with 100-300-microm particles at 12 weeks, 500-700-microm particles at 4 and 12 weeks, and 700-900-microm particles at 4 weeks). Ischemia scores were highest in the target area in all specimens. Mildly elevated ischemia scores in nontarget tissue areas were indicative of minor nontarget embolization. CONCLUSIONS: Except for small Embosphere particles at 4 weeks, the absence of inflammatory reaction to the embolization procedure or only low inflammatory changes were observed with all embolic agents, particle sizes, and follow-up intervals. Recanalization was evident with all embolic agents; however, it was pronounced with Contour SE particles.

Efficacy of a polyphosphazene nanocoat in reducing thrombogenicity, in-stent stenosis, and inflammatory response in porcine renal and iliac artery stents.

PURPOSE: It is hypothesized that the inorganic polymer poly[bis(trifluoroethoxy)phosphazene] (PTFEP) reduces stent-associated thrombosis, in-stent stenosis, and inflammatory response and stimulates reendothelialization in a porcine model. MATERIALS AND METHODS: PTFEP-nanocoated and bare stainless-steel stents (316 L) were implanted bilaterally in renal and iliac arteries of 16 minipigs (1, 4, and 12 weeks follow-up durations). Primary study endpoints were thrombogenicity determined by filling defects on angiography and in-stent stenosis assessed by lumen loss on quantitative angiography (ie, percentage stenosis) and light microscopy (ie, neointimal thickness, neointimal area, area stenosis). Secondary endpoints were inflammatory response and reendothelialization evaluated by light microscopy and scanning electron microscopy (SEM), respectively. RESULTS: Stent placement was successful in 32 renal and 26 iliac arteries. At follow-up, there were no thrombus depositions on PTFEP-coated renal and iliac stents. Thrombus depositions were found on two of six bare metal iliac stents after 4 weeks (P = .0651). PTFEP-coated stents showed a trend toward reduced in-stent stenosis in all renal and iliac arteries at all intervals: in iliac stents, neointimal area was significantly smaller in coated stents than in bare metal stents after 1 week and 4 weeks (P = .03 and P = .001, respectively). In renal arteries, inflammation scores indicated lower inflammatory response in PTFEP-coated stents than in bare metal stents after 1 week (P = .01). After 1 week, coated and bare metal stents exhibited complete reendothelialization on SEM. CONCLUSIONS: PTFEP-coated stents exhibited reduced thrombus deposition and a trend toward less in-stent stenosis and inflammatory response than bare metal stents.

Reduction of late in-stent stenosis in a porcine coronary artery model by cobalt chromium stents with a nanocoat of polyphosphazene (Polyzene-F).

The purpose of this study was to investigate the potential of nanoscale coating with the highly biocompatible polymer Polyzene-F (PZF), in combination with cobalt chromium and stainless steel stents, to reduce in-stent stenosis, thrombogenicity, and vessel wall injury and inflammation. One bare cobalt chromium, PZF-nanocoated stainless steel or PZF-nanocoated cobalt chromium stent was implanted in right coronary artery of 30 mini-pigs (4- or 12-week follow-up). Primary study end points were in-stent stenosis and thrombogenicity. Secondary study end points were vessel wall injury and inflammation as evaluated by microscopy and a new immunoreactivity score applying C-reactive protein (CRP), tumor-necrosis factor alpha (TNFalpha), and TGFbeta. At 12 weeks, angiography showed a significantly lower average loss in lumen diameter (2.1% +/- 3.05%) in PZF-nanocoated cobalt chromium stents compared with stents in the other groups (9.73% +/- 4.93% for bare cobalt chromium stents and 9.71% +/- 7% for PZF-nanocoated stainless steel stents; p = 0.04), which was confirmed at microscopy (neointima 40.7 +/- 16 lm in PZF-nanocoated cobalt chromium stents, 74.7 +/- 57.6 lm in bare cobalt chromium stents, and 141.5 +/- 109 lm in PZF-nanocoated stainless steel stents; p = 0.04). Injury and inflammation scores were low in all stents and were without significant differences. PZF-nanocoated cobalt chromium stents provided the highest efficacy in reducing in-stent stenosis at long-term follow-up. The PZF nanocoat proved to be biocompatible with respect to thromboresistance and inflammation. Our data suggest that its combination with cobalt chromium stents might provide an interesting passive stent platform.