Porcine Coronary Stent Restenosis Model Research Articles

Effects of ticagrelor on neointimal hyperplasia and endothelial function, compared with clopidogrel and prasugrel, in a porcine coronary stent restenosis model

BackgroundSeveral investigations have been conducted to evaluate the off-target effects of ticagrelor. The aim of the present study was to evaluate the off-target effects of ticagrelor such as neointimal formation and endothelial function after drug-eluting stent implantation in a porcine restenosis model. MethodsA total of 30 pigs were randomly allocated based on the following P2Y12 inhibitor: (1) clopidogrel 300mg loading plus 75mg maintenance (n=10); (2) prasugrel 60mg loading plus 10mg maintenance (n=10); (3) ticagrelor 180mg loading plus 180mg maintenance (n=10). In each group, zotarolimus-eluting stents were implanted in the proximal portion of the left anterior descending artery and left circumflex artery. One month after stenting, the animals underwent follow-up angiography, endothelial function assessment, optical coherence tomography (OCT) and histopathological analysis. ResultsRegarding vasomotor responses to acetylcholine infusion, there were significant vasoconstrictions to maximal acetylcholine infusion in the clopidogrel and prasugrel group compared with those in the ticagrelor group. The mean neointimal area were significantly lower in the ticagrelor group (1.0±0.3 by OCT, 0.9±0.3 by histology), than in the clopidogrel (1.8±0.7, p=0.003, 1.6±0.8, p=0.030) and prasugrel (1.8±0.5, p=0.001, 1.5±0.5, p=0.019) groups. Percentages of moderate to dense peri-strut inflammatory cell infiltration were significantly lower in the ticagrelor group (9.0%) compared with the clopidogrel (17.3%, p<0.001) and prasugrel groups (15.7%, p=0.002). There were no significant differences in all findings between clopidogrel and prasugrel groups. ConclusionsCompared to clopidogrel and prasugrel, ticagrelor reduced neointimal formation, endothelial dysfunction, and peri-strut inflammation.

TCTAP A-052 Effects of Ticagrelor on Neointimal Hyperplasia and Endothelial Function, Compared with Clopidogrel and Prasugrel, in a Porcine Coronary Stent Restenosis Model

TCTAP A-052 Effects of Ticagrelor on Neointimal Hyperplasia and Endothelial Function, Compared with Clopidogrel and Prasugrel, in a Porcine Coronary Stent Restenosis Model

Inhibitory Effect of Double Coating with Echinomycin and Hydrophobic Heparin in a Porcine Coronary In-Stent Restenosis Model

Stent thrombosis and in-stent restenosis are still major limitations of coronary stenting. Here, we report on a new type of drug-eluting stent (DES) aimed to prevent restenosis and thrombosis. The DES was prepared by coating a bare metal stent with echinomycin (an anti-proliferative drug) and hydrophobic heparin. The echinomycin-hydrophobic heparin double-coating stents were compared with control stents in a porcine coronary stent restenosis model. Stent overdilation injury (stent : artery=1.1 : 1.0) was compared in porcine coronary arteries between 4 groups: bare stent group (Group I, n=3), 1% echinomycin-heparin coating stent group (Group II, n=3), 5% echinomycin-heparin coating stent group (Group III, n=3), and 10% echinomycin-heparin coating stent group (Group IV, n=3). Follow-up quantitative coronary angiography was performed 4 weeks after the stents were inserted. The histopathologic assessments of the stented porcine coronary arteries were compared between the 4 groups. The neointimal areas of the stented arteries were 4.3±1.3 mm in Group I, 5.7±1.3 mm in Group II, 3.7±1.0 mm in Group III, and 2.7±1.1 mm in Group IV; the neointimal area was significantly larger in Group II than in the other groups (p<0.001). The histopathologic areas of stenosis were 61.4±18.1% in Group I, 79.8±24.0% in Group II, 52.0±18.5% in Group III, and 30.9±14.6% in Group IV; the histopathologic area was significantly smaller in Group IV than in the other groups (p<0.001). In conclusion, echinomycin-hydrophobic heparin double-coating stents effectively inhibit neointimal proliferation at a relatively high level.

Comparison of the Cobalt Alloy and Stainless Steel Core® Stent in a Porcine Coronary Restenosis Model

Background and Objectives:The stent material and thickness may influence the rate of restenosis following coronary artery stenting. A thin strut cobalt-alloy stent has been developed in an attempt to reduce the restenosis rate, while maintaining the radiopacity and radial strength. The purpose of this study was to compare a stainless steel Core stent (thickness: 90 μm/HUMED Co. Ltd, Korea) with that of a cobalt alloy Core stent (thickness: 60 μm/HUMED Co. Ltd, Korea) in a porcine coronary stent restenosis model. Materials and Methods:The cobalt alloy (Co-alloy) and stainless steel (SS) stents were implanted in 24 porcine coronary arteries. Four weeks after stenting, the pigs were sacrificed after quantitative coronary angiography (QCA). The coronary arteries were perfusion-fixed and stained, and a pathological examination performed by computer-aided histomorphometry. Results: The minimal luminal diameter at 4 weeks was larger in the Co-alloy than the SS group according to the QCA (1.8±0.8 mm vs. 2.7±0.8 mm, p=0.019). The neointimal area was significantly smaller in the Co-alloy than the SS group (1.96±0.68 mm vs. 0.89±0.27 mm, p<0.001). The intima/media area ratio was significant lower in the Co-alloy than the SS group (1.33±0.46 vs. 0.69±0.21, p=0.003). Conclusion:The thin strut cobalt alloy Core stent significantly reduces the neointimal formation compared to the stainless steel Core stent in a porcine coronary stent injury model. (Korean Circulation J 2005;35:507-512)

The effect of carvedilol-loaded biodyvYsio stent on neointimal hyperplasia in a porcine coronary stent restenosis model

The effect of carvedilol-loaded biodyvYsio stent on neointimal hyperplasia in a porcine coronary stent restenosis model

Effects of beta-radiation using a holmium-166 coated balloon on neointimal hyperplasia in a porcine coronary stent restenosis model.

Brachytherapy is a promising method of preventing and treating coronary stent restenosis. The present study was designed to observe the therapeutic effects of a radioactive balloon loaded with Holmium-166 ((166)Ho) in a porcine coronary stent restenosis model. A radioisotope of (166)Ho was coated onto the balloon surface using polyurethane (20 Gy at 0.5 mm depth). Stent overdilation injuries were induced in 2 coronary arteries in each pig (n=8). Four weeks after the injury, control balloon dilation was performed in one coronary artery (Group I) and radiation therapy using the (166)Ho coated balloon in the other coronary artery (Group II) in each pig. Follow-up coronary angiography and histopathologic assessment were performed at 4 weeks after the radiation therapy or the control balloon dilations. With regard to complete blood cell counts, liver function tests, lipid profiles and coagulation tests, there were no differences between the baseline and after radiation. On quantitative coronary angiographic analysis, reference and target artery diameter showed no differences between the 2 groups before, or 4 and 8 weeks after stenting. On histopathologic analysis of groups I and II, the injury score was 1.34+/-0.09 and 1.32+/-0.10, the area of internal elastic lamina was 4.99+/-0.17 mm(2) and 4.82+/-0.20 mm(2), and the luminal area was 3.20+/-0.10 mm(2) and 3.45+/-0.14 mm(2), respectively (p=NS). The neointimal area was 1.78+/-0.11 mm(2) in group I and 1.36+/-0.12 mm(2) in group II (p=0.017), and the histopathologic area of stenosis was 35.1+/-1.6% in group I and 27.6+/-1.9% in group II (p=0.005). In conclusion, beta-radiation of the stented porcine coronary artery using a radioactive (166)Ho coated balloon inhibited stent restenosis without any side effects.

The Effect of the Probucol-Loaded BiodivYsioTM DD Stent on Inhibition of Neointimal Proliferation in Porcine Coronary Stent Restenosis Model

Background and Objectives:In a recent multicenter trial probucol was found to reduce stent restenosis by improving the lumen dimension. The probucol was administered for 2 weeks before, and 4 weeks after, stenting. The release of the drug at the site of a vascular injury, via polymer-coated stents, helps achieve an effective local concentration. The feasibility of a probucol stent coating in reducing in-stent restenosis was assessed. Materials and Methods:The probucol loading and in vitro release were assessed using BiodivYsio stents, in a 50 mg/mL probucol solution. After being dip-coated with probucol (n=8), or a control (n=8) solution, the stents were implanted in 8 pigs. Angiography and histopathological analyses were performed 28 days later. Results:The total probucol loading was 52±16 μg/stent, with no release for up to 72 hours after loading. No pig died until sacrifice. On angiography, the reference and minimum lumen diameters showed no significant differences between the two groups, with similar diameters stenosis (8.7±3.68 vs. 13.3±4.18%, p=0.120). On histomorphometry, the injury scores, vessel, lumen and neointimal areas showed no significant differences between the groups, with similar areas of stenosis (23.1±12.39 vs. 25.2±8.22%, p=0.671). The degrees of re-endothelialization, inflammation and smooth muscle cell proliferation were not significantly different. Conclusion:Probucol can be loaded onto a polymercoated stent, and does not release from the stent for up to 72 hours after loading. About 52 μg probucol per stent does not reduce in-stent restenosis in porcine coronary arteries. (Korean Circulation J 2003;33 (11):1028-1035)

The Role of Extracellular Matrix within the Neointima in A Porcine Coronary Stent Restenosis Model

Background and Objectives:Coronary stent restenosis remains a major limitation to percutaneous coronary intervention. The most important mechanism of coronary stent restenosis is neointimal hyperplasia (NIH). In addition to neointimal cell proliferation, extracellular matrix (ECM) synthesis may be important in the induction of NIH. We sought to observe the degree of this in a porcine model. Subjects and Methods: Twenty-one coronary stents were placed in 15 pigs, and the pigs were sacrificed at 14 (Group I), 28 (Group II) and 56 (Group III) days following stenting. The twenty-one coronary stents were classified into three groups, followed by histopathological analyses of 7 stented arteries. Each specimen was analyzed by HEp=0.08, p=0.03). The pathological area stenoses were 18.8±7.4, 34.2±0.2 and 43.1±28.4% in Groups I, II and III, respectively (Group I vs. II and Group I vs. III;p=0.35, p=0.02). The PCNA indices of neointima were 16.5±14.4, 0.5 ±0.74 and 0.83±0.68% in Groups I, II and III, respectively (Group I vs. II and Group I vs. III;p=0.01). The collagen content ratios within the neointima were 23.5±4.7, 27.7±5.0 and 36.6±10.5% in Groups I, II and III, respectively (Group I vs. II and Group I vs. III;p=0.52, p=0.01). Proteoglycans were abundant in Groups I and II, and alpha-actin was positive in the neointima cells. Conclusion:The role of cell proli논문접수일:2002년 09월 30일 심사완료일:2002년 11월 28일 교신저자:정명호, 501-757 광주광역시 동구 학1동 8번지 전남대학교 의과대학 전남대학교병원 심장센터 전화:(062) 220-6243·전송:(062) 228-7274·E-mail:myungho@chollian.net

Intramural coronary delivery of advanced antisense oligonucleotides reduces neointimal formation in the porcine stent restenosis model

ObjectivesWe evaluated the long-term influence of intramural delivery of advanced c-myc neutrally charged antisense oligonucleotides (Resten-NG) on neointimal hyperplasia after stenting in a pig model. BackgroundNeointimal hyperplasia after percutaneous coronary interventions is one of the key components of the restenotic process. The c-myc is a critical cell division cycle protein involved in the formation of neointima. MethodsIn short-term experiments, different doses (from 500 μg to 5 mg) of Resten-NG or saline were delivered to the stent implantation site with an infiltrator delivery system (Interventional Technologies, San Diego, California). Animals were euthanized at 2, 6 and 18 h after interventions, and excised vessels were analyzed for c-myc expression by Western blot. In long-term experiments, either saline or a dose of 1, 5 or 10 mg of Resten-NG was delivered in the same fashion, and animals were euthanized at 28 days after the intervention. ResultsWestern blot analysis demonstrated inhibition of c-myc expression and was dose dependent. Morphometry showed that the intimal area was 3.88 ± 1.04 mm2in the control. There was statistically significant reduction of intimal areas in the 5 and 10 mg groups (2.01 ± 0.66 and 1.95 ± 0.91, respectively, p < 0.001) but no significant reduction in the 1 mg group (2.81 ± 0.56, p > 0.5) in comparison with control. ConclusionsThis study demonstrated that intramural delivery of advanced c-myc neutrally charged antisense morpholino compound completely inhibits c-myc expression and dramatically reduces neointimal formation in a dose dependent fashion in a porcine coronary stent restenosis model, while allowing for complete vascular healing.

The Effects of Beta-Radiation Using a Holmium-166 Coated Balloon on Neointimal Hyperplasia in a Porcine Coronary Stent Restenosis Model

The Effects of Beta-Radiation Using a Holmium-166 Coated Balloon on Neointimal Hyperplasia in a Porcine Coronary Stent Restenosis Model

Comparison of Core(R) stent and Palmaz-Schatz(R) stent in a Porcine Stent Restenosis Model

Background and Objectives：The purpose of this study is to compare the new Core ® stent and PalmazSchatz ® (PS stent in a porcine coronary stent restenosis model. Methods：Twelve pigs underwent balloon injury followed by implantation of oversized, tubular-type Core ® and PS ® stents (stent/artery ratio 1.2：1 in twenty-four coronary arteries. Quantitative analyses of the initial and follow-up coronary angiograms at 4 weeks after stenting was performed. The extents of injury and the neointimal area were compared between the two stented groups according to morphometric analysis. The stent flexibility and longitudinal staightening effect were compared between the two groups by the bending test and measurement of the angle changes. Results：1 The reference vessel diameter, stented artery diameter, and diameter of the stenosis were not different between the two groups. 2 The neointimal area was significantly smaller in the Core ® stent group than in the PS ® stent group (1.81±0.67 mm 2 vs 2.93±0.94 mm 2 , p＝0.006. 3 The Core ® stent had more flexible property than the PS ® stent. 4 The angle changes following stent implantation did not differ between the two groups(13.2±9.0, 14.4±11.1, p＝0.88. Conclusion：Core ® stent is effective in the inhibition of neointimal formation in a porcine coronary stent restenosis model. These results may be due to the improved flexibility of the Core ® stent, although further clinical trials may be needed. (Korean Circulation J 2001; 31(7 :655-661