1.Investigation of long-term implantation of BuMA stent in a porcine coronary model.
Ming CHEN ; Xin-gang WANG ; Bo ZHENG ; Hong-yu PENG ; Xiao-yan ZHANG ; Bin ZHANG ; Yong HUO
Chinese Medical Journal 2012;125(22):4083-4087
BACKGROUNDStent-based delivery of sirolimus has been shown to reduce neointimal hyperplasia significantly. However, the long-term effect of the polymer is thought to initiate and sustain an inflammatory response and contribute to the occurrence of late complications. Our study aimed to evaluate the efficacy and safety of the BuMA biodegradable drug-coated sirolimus-eluting stent (BSES) for inhibiting neointimal hyperplasia in a porcine coronary model.
METHODSFour types of stents were implanted at random in different coronary arteries of the same pig: BSES (n = 24), bare metal stent (BMS) (n = 24), biodegradable polymer coated stent without drug (PCS) (n = 24) and only poly (n-butyl methacrylate) base layer coated stent (EGS) (n = 23). In total, 26 animals underwent successful random placement of 95 oversized stents in the coronary arteries. Coronary angiography was performed after 28 days, 90 days and 240 days of stent implantation. After 14 days, 28 days, 90 days and 240 days, 6 animals at each timepoint were sacrificed for histomorphologic analysis.
RESULTSThe 28-day, 90-day and 240-day results of quantitative coronary angiography (QCA) showed reduction in luminal loss (LL) in the BSES group when compared with the BMS group; (0.20 ± 0.35) mm vs. (0.82 ± 0.51) mm (P = 0.035), (0.20 ± 0.30) mm vs. (0.93 ± 0.51) mm (P = 0.013), and (0.18 ± 0.16) mm vs. (0.19 ± 0.24) mm (P = 0.889), respectively. By 28-day, 90-day and 240-day histomorphomeric analysis results, there was also a corresponding significant reduction in neointimal tissue proliferation with similar injury scores of BSES compared with the BMS control; average neointimal area (0.90 ± 0.49) mm(2) vs. (2.16 ± 1.29) mm(2) (P = 0.049), (1.53 ± 0.84) mm(2) vs. (3.41 ± 1.55) mm(2) (P = 0.026), and (2.43 ± 0.95) mm(2) vs. (3.12 ± 1.16) mm(2) (P = 0.228), respectively. High magnification histomorphologic examination revealed similar inflammation scores and endothelialization scores in both the BSES and BMS groups.
CONCLUSIONSThe BuMA biodegradable drug-coated sirolimus-eluting stents can significantly reduce neointimal hyperplasia and in-stent restenosis. Re-endothelialization of the BuMA stent is as good as that of the BMS in the porcine coronary model due to the reduced inflammation response to the BuMA stent.
Absorbable Implants ; Animals ; Coronary Angiography ; Drug-Eluting Stents ; Female ; Hyperplasia ; pathology ; Neointima ; prevention & control ; Polymers ; chemistry ; Sirolimus ; therapeutic use ; Swine
2.Comparison of Optical Coherence Tomographic Assessment between First- and Second-Generation Drug-Eluting Stents.
Byeong Keuk KIM ; Jung Sun KIM ; Junbeom PARK ; Young Guk KO ; Donghoon CHOI ; Yangsoo JANG ; Myeong Ki HONG
Yonsei Medical Journal 2012;53(3):524-529
PURPOSE: There is a lack of sufficient data in comparison of optical coherence tomographic (OCT) findings between first- and second-generation drug-eluting stents (DES). Compared to first-generation (i.e., sirolimus- or paclitaxel-eluting stents), second-generation DESs (i.e., everolimus- or biolinx-based zotarolimus-eluting stents) might have more favorable neointimal coverage. MATERIALS AND METHODS: Follow-up OCT findings of 103 patients (119 lesions) treated with second-generation DESs were compared with those of 139 patients (149 lesions) treated with first-generation DESs. The percentage of uncovered or malapposed struts, calculated as the ratio of uncovered or malapposed struts to total struts in all OCT cross-sections, respectively, was compared between the two groups. RESULTS: Both DES groups showed similar suppression of neointimal hyperplasia (NIH) on OCT (mean NIH cross-sectional area; second- vs. first-generation=1.1+/-0.5 versus 1.2+/-1.0 mm2, respectively, p=0.547). However, the percentage of uncovered struts of second-generation DESs was significantly smaller than that of first-generation DESs (3.8+/-4.8% vs.7.5+/-11.1%, respectively, p<0.001). The percentage of malapposed struts was also significantly smaller in second-generation DESs than in first-generation DESs (0.4+/-1.6% vs.1.4+/-3.7%, respectively, p=0.005). In addition, intra-stent thrombi were less frequently detected in second-generations DESs than in first-generation DESs (8% vs. 20%, respectively, p=0.004). CONCLUSION: This follow-up OCT study showed that second-generation DESs characteristically had greater neointimal coverage than first-generation DESs.
Aged
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Coronary Angiography
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*Drug-Eluting Stents
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Female
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Humans
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Male
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Middle Aged
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Neointima/pathology/prevention & control
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Tomography, Optical Coherence/*methods
3.Recombinant human interleukin-10 inhibits proliferation of vascular smooth muscle cells stimulated by advanced glycation end products and neointima hyperplasia after carotid injury in the rat.
Ping OUYANG ; Li-Sheng PENG ; Hong YANG ; Wen-Lie PENG ; Wen-Yan WU ; An-Long XU
Acta Physiologica Sinica 2003;55(2):128-134
The purposes of this study was to determine the effects of recombinant human interleukin-10 (rhIL-10) on proliferation of vascular smooth muscle cells (VSMCs) stimulated by advanced glycation end products (AGE) and neointima hyperplasia after rat carotid arterial injury. Rat aortic VSMCs were cultured and treated with rhIL-10 or AGE respectively, and then co-treated with rhIL-10 and AGE. Proliferation of VSMCs was quantified by colormetric assay. Cell cycle analysis was performed by flow cytomertry. Sprague-Dawley rats were treated with recombinant human IL-10 (rhIL-10) for 3 d after carotid arteries injury. The ratio of neointima to media area at the site of arterial injury was measured 28 d after balloon injury. The p44/42 MAPK activity was evaluated by the immunoblotting technique using anti-p44/42 phospho-MAPK antibody. Compared to control, AGE stimulated VSMCs proliferation. rhIL-10 alone had no effect on VSMCs growth. With AGE stimulation, rhIL-10, at dose as low as 10 ng/ml, inhibited VSMCs growth (P<0.05). The cell number in G(0)/G(1) phase of AGE and rhIL-10 co-treatment group was higher than that of AGE treatment alone (P<0.01) by flow cytometry analysis. Compared with the control group of neointima hyperplasia in rats, the ratio of neointima to media area of recombinant human IL-10 group was reduced by 45% (P<0.01). The p44/42 MAPK activity was significantly enhanced by AGE. The AGE effects were opposed by rhIL-10. The anti-inflammatory cytokine rhIL-10 inhibits AGE-induced VSMCs proliferation. Recombinant human IL-10 also inhibited neointima hyperplasia after carotid artery injury in rats. The results suggest the possibility that recombinant human IL-10, as a potential therapeutic approach, prevents neointimal hyperplasia.
Animals
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Aorta, Thoracic
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cytology
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Atherosclerosis
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physiopathology
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Carotid Artery Injuries
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pathology
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physiopathology
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Carotid Intima-Media Thickness
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Cell Proliferation
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drug effects
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Cells, Cultured
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Glycation End Products, Advanced
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antagonists & inhibitors
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pharmacology
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Hyperplasia
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prevention & control
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Interleukin-10
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pharmacology
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Male
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Muscle, Smooth, Vascular
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cytology
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Myocytes, Smooth Muscle
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drug effects
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Neointima
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drug therapy
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prevention & control
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins
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pharmacology
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Tunica Intima
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pathology