^192Ir高线量率血管腔内照射对抑制兔血管平滑肌细胞增殖及新生内膜过度增生的研究

目的 研究^192I搞线量率血管腔内照射对用切割球囊导管行经皮血管腔内成形术（PTA）后的日本白兔髂动脉平滑肌细胞增殖抑制的经时反应和效果。方法 20只日本白兔经左侧颈总动脉放置切割球囊导管行髂动脉PTA术，随机于一侧髂动脉施行12Gy剂量的血管腔内照射，非照射侧作为对照侧。实验动物于术后1、2、3、4、8及12周处死。根据新生内膜的形成情况，血管成形术后接受血管腔内照射的血管段按时间分为3组：即1周组5只、2－4周组9只、8－12周组6只。随后对标本进行了组织病理、形态学测量和免疫组织化学分析。结果 1周时，与照射侧比较，对照侧血管段创口修复处可明显的新生内膜增生，新生内膜中抗增殖细胞核抗原（PCNA）阳性细胞率呈一峰值；2－4周期间，与对照侧比较，照射侧血管段新生内膜增生明显减弱（P＜0．01），新生内膜中PCNA阳性细胞率较对照侧低，差异有显著性意义（P＜0．01）；8－12周，照射侧血管段增生的新生内膜较对照侧仍处较低水平，新生内膜中PCNA阳性细胞率约低于1％。经抗平滑肌细胞α胶原免疫组织化学染色，证实新生内膜中主要为平滑肌细胞。结论 由照射所致的新生内膜增生过程的抑制作用从开始时即已启动。12Gy的^192Ir高线量率照射能有效地抑制用切割球囊导管损伤引起的日本白兔髂动脉新生内膜的过渡增生。     

曲尼司特对兔髂动脉损伤后内膜增殖及血管重构的影响

目的　探讨曲尼司持对兔髂动脉球囊损伤后内膜增殖及血管重构的影响。方法　 2 4只新西兰大白兔随机分为假手术组、对照组和用药组。用球囊导管对用药组和对照组兔行髂动脉损伤。用药组于术前 3d开始用曲尼司特 (每天 30 0mg/kg) ,术后 2 8d取病变血管苏木精 伊红和弹力纤维染色并免疫组化检查 ,以计算机图像分析血管内膜、中膜厚度、管腔面积、平均动脉面积 (外弹力膜内横截面积 ,EEL)的变化 ,计算增殖细胞核抗原 (PCNA)增殖指数 (PI)。结果　曲尼司特显著减少内膜厚度 ,增加血管腔面积和平均动脉面积 ,对中膜厚度无明显影响。曲尼司特使内膜PCNA阳性细胞百分比降低。结论　曲尼司特能抑制兔髂动脉球囊损伤后内膜增殖 ,促进代偿性血管扩张。其抑制内膜增生可能与抑制血管平滑肌细胞增殖有关     

188 Re液体血管内照射防治血管内膜损伤后再狭窄的实验研究

目的　研究1 88Re液体充盈球囊导管对兔血管再狭窄模型用不同剂量内照射后对增生内膜不同的剂量效应。方法　 16只新西兰白兔分成 2组 ,一侧下肢髂动脉行内膜剥脱术后 ,通过直径 2 5mm液体1 88Re充盈球囊导管分别给以 0、8和 15Gy剂量的血管内照射治疗。其中 8只兔的另一侧髂动脉仅行内膜剥脱术作为对照。 4周后处死动物 ,取出血管。组织经HE染色、VanGieson胶原染色、α 肌动蛋白免疫组化染色 ,通过图像分析系统分析 ,测定狭窄指数和增殖指数。结果　对照组、8和 15Gy组的狭窄指数分别为 0 49± 0 0 6、0 65± 0 0 5和 0 82± 0 0 5 ,增殖指数分别为 0 5 4±0 0 9、0 48± 0 0 6和 0 3 3± 0 0 4。 15Gy组增生的内膜明显下降 (P <0 0 5 ) ,而 8Gy组与对照组比较差异无显著性 (P >0 0 5 )。免疫组化显示增生的内膜主要是平滑肌细胞 (SMCs)。结论　在兔血管再狭窄模型中 ,用1 88Re液体充盈球囊导管内照射治疗 ,当接近血管内表面的吸收剂量达到 15Gy时能安全有效地抑制内膜平滑肌的增生     

32P液体球囊血管内照射预防血管成形术后再狭窄

目的 探讨^32P液体球囊血管内近距离照射治疗对防止血管成形术后再狭窄的量效关系及其抑制再狭窄发生的可能机制。方法 27只雌性大白兔据动脉球囊扩张损伤后，实验组(18只)分别给予3、9、18和36Gy^32P液体球囊行内照射治疗，对照组(9只)灌注生理盐水。术后于不同时间点取材，行HE染色、增殖细胞核抗原(PCNA)免疫组织化学染色以及电镜观察血管组织形态学的改变，用计算机图像分析法测量管腔面积和内膜面积。结果 对照组血管内膜明显增生，管腔变狭窄。18Gy组血管壁平滑肌细胞增殖明显受抑，细胞凋亡增加，管腔面积无明显丢失；36GY组血栓形成明显；3和9Gy组均未观察到明显的生物效应。结论 ^32P液体球囊血管内照射可防止血管成形术后再狭窄发生，其机制可能为抑制血管壁平滑肌细胞增殖，促进其凋亡及改善血管重塑形。     

188Re灌注球囊照射预防兔血管再狭窄

目的观察188Re灌注球囊血管内照射对兔血管损伤后再狭窄的预防作用.方法应用球囊过度扩张损伤兔双侧髂动脉,随机选择一侧髂动脉进行188Re灌注球囊血管内局部照射,对受照射血管进行血管造影、组织病理学检查及增殖细胞核抗原(PCNA)染色分析.结果与非照射组血管比较,照射组血管直径较大[(1.94±0.19) vs (1.77±0.28) mm,P<0.05],新生内膜面积减少[(1.12±0.75) vs (2.17±1.21) mm2,P<0.01],狭窄面积百分比降低[(19.23±12.60)% vs (34.45±17.49)%,P<0.01],PCNA阳性率低[(3.75±2.09)% vs (5.64±1.74)%,P<0.05].0.5 mm深处组织吸收剂量为15 Gy.结论 188Re灌注球囊血管内照射能够抑制兔损伤血管再狭窄.     

κB抑制蛋白基因对血管内支架植入术后内膜增生抑制作用的实验研究

目的　观察血管内局部转移腺病毒携带的IκBα基因对兔髂动脉内支架植入术后内膜增生的抑制作用。方法　 12只杂种新西兰大白兔 ,2 4支髂动脉 ,随机 (计算机 )分为转基因组、磷酸盐缓冲液 (PBS)对照组和空白对照组 (各组均为 8支髂动脉 )。转基因组髂动脉于支架植入术后 ,经多隧道球囊导管输送腺病毒携带的IκBα基因行局部转基因治疗 ;PBS对照组于髂动脉支架植入术后 ,局部注射PBS ;空白对照组则仅行髂动脉内支架植入术。分别于术后 1周和 4周 6只兔重复髂动脉造影 ,之后再处死动物 ,取支架植入处动脉作病理检查 ,分近、中、远 3段 ,测量新生内膜截面积等。结果术后 1周和 4周造影显示各组的管腔内径间差异均无显著性意义 (F =0 .0 5 ,2 .71;P >0 0 5 ) ,但术后4周 ,各组新生内膜截面积分别为 (2 2 8± 0 14 )mm2 ,(3 2 6± 0 2 5 )mm2 ,(2 80± 0 2 0 )mm2 ,转基因组明显小于对照组 (F =5 .0 7,P <0 0 5 )。结论　血管内局部转移腺病毒携带的IκBα基因可以抑制兔髂动脉内支架植入术后的内膜增生 ,从而可能降低支架植入术后再狭窄的发生率     

双向内膜下血管成形术在治疗下肢动脉闭塞症中的应用

目的 探讨双向内膜下血管成形术在治疗周围动脉完全闭塞性病变中的意义。方法 采用双向内膜下血管成形术治疗5例长段动脉闭塞患者,其中腹主动脉下端合并两侧髂总动脉及髂外动脉闭塞1例,髂外动脉闭塞2例,股浅动脉闭塞2例。在单向内膜下再通时,进入真腔失败后而在患肢闭塞动脉远端血管穿刺,使用导丝从病变对侧进入闭塞段内膜下,在病变内膜下腔,采用导丝贯穿至对侧导管技术,成功后,将导丝从对侧导管引出体外,然后用球囊扩张成型并植入支架。结果 本组5例患者均成功完成双向内膜下再通,共植入支架9枚。结论 双向内膜下再通可以作为单向内膜下再通进入真腔失败时的补救方法,可有效提高血管成形术的成功率。     

小肠黏膜下层促进经皮血管腔内支架植入术后内皮化的实验研究

目的探讨小肠黏膜下层(SIS)促进支架表面内皮化在预防经皮血管腔内支架植入术(PTS)后再狭窄的价值。方法 14头猪经颈动脉球囊过度扩张双侧髂动脉后,随机选取一侧髂动脉植入裸支架(bare stent,BS),对侧髂动脉植入SIS覆膜支架(SCS)。于4、8、12周分别对4、5、5头猪进行造影复查,并处死,对支架段标本行病理组织学及扫描电镜观察。结果 14头猪(28支髂动脉)共成功植入14枚BS及14枚SCS支架。复查造影示,8周时SCS组和BS组各有1支动脉闭塞,其余26枚支架均通畅,4、8、12周时SCS组再狭窄率与BS组比较差异均无统计学意义(P<0.05)。免疫组化示4、8、12周时SCS组增殖细胞核抗原阳性细胞平均百分率均明显低于BS组(P<0.05);电镜见SCS组新生内膜内皮细胞数均高于BS组,组间差异有统计学意义(P<0.05)。结论 SIS具有促进内皮细胞再生及支架表面内皮化的作用,可间接抑制血管平滑肌细胞增殖,并促进合成型平滑肌细胞向收缩型转变的作用。     

激光对兔损伤性血管内膜增殖的抑制作用

目的　观察５１０－６ ｎｍ 波长激光对兔损伤性血管内膜增殖的抑制作用。方法　实验用雄性日本大耳白兔１２ 只,用球囊导管剥脱腹主动脉内皮,并将其分成激光照射段和对照段,随后用柱状光导纤维以１００Ｊ／ｃｍ２ 的光剂量对照射段进行照射,于术后１４ 天取材,光镜观察血管形态变化,计算机图像分析确定新生血管内膜的面积。结果　激光照射段和对照段腹主动脉均有明显的新生血管内膜形成,呈同心性增厚,厚度不均一。内膜中细胞形态和排列不规则。激光照射段血管新生内膜的平均面积为５－２ ｍｍ２ ±０－６ ｍｍ２ ;对照段为１８－３ ｍｍ２ ±１－１ ｍｍ２ ,两者差异有非常显著意义（Ｐ＜０－０１）。结论　５１０－６ ｎｍ 波长激光照射能显著抑制损伤性血管内膜的增殖,有望用于再狭窄的防治。     

高胆脂血症兔血管再狭窄模型动脉β内照射诱导平滑肌细胞凋亡及减少中膜细胞构成

目的 :几种经皮冠状动脉血管成形术后再狭窄动物模型均表明 ,电离辐射对动脉损伤后新内膜的增生有较强的抑制作用 ,这一观点最早被认为和平滑肌细胞有丝分裂活性降低有关。本研究用于评价血管 β内照射对动脉壁平滑肌细胞密度及凋亡的影响。方法 :利用 Baum gartner技术获得高胆脂血症新西兰大白兔的损伤性颈动脉 2 5根和 7根髂动脉 ,在球囊损伤后给予 18Gy的 90 Yβ内照射 ,其结果与单纯损伤未经照射的对照组进行比较。损伤后第 8天、第 2 1天和 6周时 ,利用计算机自动处理软件分析中膜平滑肌细胞密度和凋亡细胞比例 ,凋亡细胞通过原位末…     

血管内放射治疗对平滑肌细胞增殖与凋亡的影响

目的：观察血管内放射治疗（简称放疗）对受损动脉平滑肌细胞（SMC）增殖与凋亡的影响。方法：用^192Ir后装源对猪受损髂动脉进行不同剂量血管内放疗，通过免疫组织化学增殖细胞核抗原（PCNA）与三磷酸脱氧尿嘧啶缺口末端标记法（TUNEL）检测不同时间点血管SMC增殖与凋亡情况。结果：放疗组第3天起中膜SMC增殖明显受抑及凋亡增加（P均＜0．05）；第10天时内膜SMC增殖明显减弱，20Gy组内膜SMC凋亡率显著增加；第28天时内膜SMC增殖明显受抑，凋亡率增加（P均＜0．05），20Gy组较10Gy组明显（P＜0．05）。结论：血管内放疗可抑制动脉损伤后SMC增殖、促进SMC凋亡。     

Comparative trial of local pharmacotherapy with L-arginine, r-hirudin, and molsidomine to reduce restenosis after balloon angioplasty of stenotic rabbit iliac arteries

PURPOSE: To determine if local application of L-arginine, r-hirudin, or molsidomine significantly reduces restenosis after balloon angioplasty in stenotic rabbit iliac arteries. MATERIALS AND METHODS: Thirty-one male cholesterol-fed New Zealand white rabbits underwent balloon dilation of both common iliac arteries to induce arterial stenosis. Four weeks later, one stenotic iliac artery was simultaneously dilated and received local application of L-arginine (210 mg/mL, n = 7), r-hirudin (0.5 mg/mL, n = 8), or molsidomine (0.2 mg/mL, n = 8) with a channeled balloon catheter. On the contralateral side, 0.9% saline was injected as a control. In eight sham animals, saline was applied to one iliac artery and balloon dilation to only the contralateral artery. Six weeks after local treatment, vessels were harvested, and computerized morphometric and immunohistologic analyses were performed. RESULTS: Application of drugs resulted in a significant reduction of neointimal area as follows: 53% with L-arginine (1.01 mm(2) vs. 2.17 mm(2), P <.05), 43% with molsidomine (1.04 mm(2) vs. 1.89 mm(2), P <.05), and 20% with r-hirudin (1.79 mm(2) vs. 2.24 mm(2), P <.05). Infusion of saline led to a significant increase (50%, 1.21 mm(2) vs. 1.93 mm(2), P <.05) in neointimal area compared with balloon dilation alone. Immunohistologic findings showed a significant reduction of macrophages (5.0% vs. 10.2%, P <.05) and proliferating cells (6.2% vs. 10.6%, P <.05) in the neointima after local application of L-arginine. CONCLUSION: Reduction of neointimal area was significant for L-arginine and molsidomine but not for r-hirudin. Saline infusion caused significant arterial trauma, resulting in additional neointimal proliferation.     

Effect of transcatheter endovascular radiation with holmium-166 on neointimal formation after balloon injury in porcine coronary artery

BACKGROUND: Neointimal formation in response to arterial injury is a major contributing element in restenosis after coronary balloon angioplasty and stenting. Endovascular irradiation has been reported to be effective in reducing restenosis. The purpose of this study was to investigate the effect of beta-emitting holmium-166 for the inhibition of neointimal formation in porcine coronary artery. METHODS AND RESULTS: A total of 34 pigs weighing 25 to 30 kg underwent oversized balloon injury (balloon/artery ratio, 1.3:1.4) at the proximal portion of the left anterior descending and circumflex arteries. One artery was randomly assigned to receive radiation after injury. Ho-166 was left in the balloon within the delivery catheter for a period sufficient to deliver 9 Gy and 18 Gy to a depth of 1 mm from the surface of the balloon. Four weeks later, pigs were sacrificed and hearts were perfusion-fixed, followed by histopathologic analysis and planimetry for measurement of maximal intimal thickness, intimal area, and fracture length. The coronary segment of the pigs in the control group had neointimal area of 1.18+/-0.55 mm2; the pigs in the 9-Gy group had neointimal area of 0.68+/-0.40 mm2 (P<.05 vs. control); and the pigs in the 18-Gy group had neointimal area of 0.29+/-0.12 mm2 (P<.01 vs. control). The maximal intimal thickness in the 18-Gy group (0.14+/-0.11 mm) was significantly reduced compared with the maximal intimal thickness in the control group (0.48+/-0.13 mm) (P<.01). CONCLUSIONS: Intracoronary radiation with liquid Ho-166 contained in a perfusion balloon catheter is feasible and effective in reducing neointimal formation after coronary overstretch injury in pigs. Therefore intracoronary irradiation on the injured segment may further reduce restenosis after balloon injury.     

Increased expression of nuclear NF-kappaB after coronary artery balloon injury can be inhibited by intracoronary beta-irradiation

PURPOSE: Molecular mechanisms by which balloon angioplasty injury-induced neointimal hyperplasia can be reduced by intravascular brachytherapy are unclear. We investigated the role of nuclear factor-kappaB (NF-kappaB) in neointimal hyperplasia following intracoronary irradiation. MATERIALS AND METHODS: Fifty-four coronary arteries from 30 pigs were divided into 6 groups: sham control, balloon angioplasty injury alone, beta-irradiation at doses of 14 or 20 Gy, and 14 or 20 Gy beta-irradiation immediately followed by balloon injury. Coronary arteries were injured by overstretch balloon angioplasty and then the arteries were irradiated using a Rhenium-188 ((188)Re) beta-emitting solution-filled balloon. Pigs were scarified one day or one week after coronary interventions for molecular detection and six weeks after the procedures for histological examination. RESULTS: Six weeks after coronary interventions, the histological results show that balloon angioplasty injury had induced intimal hyperplasia in coronary artery but the response was significantly reduced by 28% and 60% when the injury was immediately treated by 14 and 20 Gy (188)Re beta-irradiation, respectively. The expression of arterial NF-kappaB p65, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were detected at one day and one week after the procedures. The treatment of balloon injury could significantly induce the NF-kappaB p65 expression in both gene and protein levels, and such induction could be significantly reduced by (188)Re beta-irradiation at dose of 20 Gy. However, the similar result on the regulation of gene expression affected by the beta-irradiation could not be observed in ICAM-1 and VCAM-1. CONCLUSION: The inhibitory effect of intracoronary brachytherapy on neointimal formation following overstretch balloon angioplasty could involve inhibition of NF-kappaB p65.     

Increased expression of nuclear NF-kappaB after coronary artery balloon injury can be inhibited by intracoronary beta-irradiation

Purpose: Molecular mechanisms by which balloon angioplasty injury-induced neointimal hyperplasia can be reduced by intravascular brachytherapy are unclear. We investigated the role of nuclear factor-kappaB (NF-κB) in neointimal hyperplasia following intracoronary irradiation.

Materials and methods: Fifty-four coronary arteries from 30 pigs were divided into 6 groups: sham control, balloon angioplasty injury alone, β-irradiation at doses of 14 or 20 Gy, and 14 or 20 Gy beta-irradiation immediately followed by balloon injury. Coronary arteries were injured by overstretch balloon angioplasty and then the arteries were irradiated using a Rhenium-188 (¹⁸⁸Re) β-emitting solution-filled balloon. Pigs were scarified one day or one week after coronary interventions for molecular detection and six weeks after the procedures for histological examination.

Results: Six weeks after coronary interventions, the histological results show that balloon angioplasty injury had induced intimal hyperplasia in coronary artery but the response was significantly reduced by 28% and 60% when the injury was immediately treated by 14 and 20 Gy ¹⁸⁸Re β-irradiation, respectively. The expression of arterial NF-κB p65, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were detected at one day and one week after the procedures. The treatment of balloon injury could significantly induce the NF-κB p65 expression in both gene and protein levels, and such induction could be significantly reduced by ¹⁸⁸Re β-irradiation at dose of 20 Gy. However, the similar result on the regulation of gene expression affected by the β-irradiation could not be observed in ICAM-1 and VCAM-1.

Conclusion: The inhibitory effect of intracoronary brachytherapy on neointimal formation following overstretch balloon angioplasty could involve inhibition of NF-κB p65.     

Effects of nitinol Strecker stent placement on vascular response in normal and stenotic porcine iliac arteries

PURPOSE: This experimental study was conducted to evaluate neointimal thickness, lumen diameters, and histologic changes in normal and stenotic porcine iliac arteries following placement of self-expanding nitinol Strecker stents. MATERIALS AND METHODS: Neointimal trauma causing slight vascular stenosis was induced unilaterally within external iliac arteries of 12 swines by means of endothelial abrasion and high cholesterol diet. Nitinol Strecker stents were placed within the stenotic and the normal contralateral vascular segments. For histopathologic evaluation, the pigs were killed 12 or 24 weeks after stent placement and luminal diamters were evaluated angiographically. RESULTS: Excluding one occlusion, 15% narrowing of the lumen diameter was induced unilaterally (P = .002). Initial luminal gain after stent placement was greater for stenotic than for normal arteries. The amount of neointima thickness was not different between stenotic and normal vessels (P > .05). Comparing vascular diameters before stent placement and at follow-up, luminal loss due to neointima proliferation was 22% within normal arteries (P = .0002), while a luminal gain by 15% was found within the stenotic arteries (P = .008). Maturation of neointima and endothelial coverage were complete after 24 weeks. CONCLUSIONS: Even though nitinol Strecker stents induce excessive neointimal proliferation, stenotic arteries seem to profit from great early luminal gain resulting in 15% of vascular expansion at follow-up while slight stenosis is induced within normal iliac arteries.     

Monte Carlo dose simulation for intracoronary radiation therapy with a rhenium 188 solution-filled balloon with contrast medium

BACKGROUND: The therapeutic efficacy of percutaneous transluminal coronary angioplasty is limited by the incidence of restenosis. Intracoronary irradiation has shown to be effective in restenosis control by inhibiting the neointimal proliferation. METHODS AND RESULTS: Monte Carlo simulation has been performed to calculate the dose to the vessel wall for intracoronary irradiation with a rhenium 188 solution-filled balloon for restenosis inhibition. With a 3-mm-diameter and 30-mm-long balloon, the radiation dose at 1 mm from the balloon surface was 5.3% lower when the balloon structure was included in geometric modeling of the angioplasty catheter, as compared with that obtained by ignoring the structure. The additional dose reduction due to Hexabrix 320 contrast medium added in 30% of volume ratio was 4.7%. With regard to axial dose distribution, the dose was uniform over the balloon length except near the balloon end, at which the dose was reduced by 35% at a 1-mm-deep layer in the vessel wall. With the Re-188 solution mixed with 30% of Hexabrix 320 in volume ratio, the Re-188 activity to be injected for delivery of 15 Gy to the 1-mm-deep layer by 1-minute irradiation was 27.3 GBq/mL. CONCLUSIONS: Dose estimates produced in this study should be helpful in determining the Re-188 activity to be injected or the irradiation time for a varying situation in terms of length and diameter of the irradiated arterial segment and depth of the target layer.     

Short-term effects of a new intravascular nitinol stent in canine arteries

RATIONALE AND OBJECTIVES: To evaluate the short-term effects of a new nitinol stent on canine arteries. METHODS: Eighteen nitinol mesh stents were placed in abdominal aortas, common iliac arteries, and renal arteries of six dogs. Angiography was performed to evaluate the patency rates and structural changes of arteries at 1 day, 3 weeks, 4 weeks, and 10 weeks after stent insertion. Gross and light microscopic examinations were performed after angiography. RESULTS: On angiography, the patency rate was 100%, and no thrombosis was observed. All side branches from stented segments were patent. The mean neointimal thickness over and between stent wires was 94 and 167 microns. No difference was found between the aorta and the small vessels. Histologically, the neointima was covered with endothelium and was composed of subintimal fibrosis with mild inflammation. CONCLUSIONS: The new type of nitinol mesh stent showed a high patency rate, with no thrombosis and relatively thin neointimal proliferation.     

4 years' experience with a balloon-expandable endoprosthesis. Experimental and clinical application]

During a 4-year period of clinical application of the balloon-expandable Palmaz stent, a randomized trial comparing stent implantation and traditional balloon angioplasty of iliac arteries in arterial occlusive disease was started. The first long-term results, recorded after 2 years, indicate statistically significant differences in the complication rate (after stenting 2/62 and after angioplasty 5/69) and patency (greater than or equal to 70% of original lumen size upon stent implantation or balloon inflation: 95% after stenting and 72% after angioplasty). Clinical improvement after 2 years was 89% after stenting and 70% after angioplasty. Parallel to the clinical trials, experimental canine artery stenting was performed to evaluate differences in the long-term patency of stents exposed to restricted flow. Significant differences in neointimal healing were found between normally perfused stents and stents with artificially reduced flow: during the total observation period of 6 months the neointimal height was up to 200% higher in flow-restricted stents, while the histological composition of the neointima was the same as with normally perfused stents.