血管内放射治疗预防血管成形术后再狭窄

血管内放射治疗预防血管成形术后再狭窄是老技术新用途。ＲＳ形成主要是血管损伤后，管壁组织细胞增殖修复过度所致，血管内放射治疗通过抑制细胞增殖来达到预防ＲＳ，在实验室中效果良好，并已迅速进入临床应用研究。     

血管内近距离照射预防血管成形术后再狭窄

在防治经皮冠状动脉介入治疗（PCI）后再狭窄的方法中，血管腔内近距离照射逐渐成为一种极有前途的新方法。近年来，在血管内照射的机制、放射源种类、剂量、动物和临床实验及安全性等方面取得了重大进展。目前看来，该方法有效且安全可行。     

雌激素在预防血管成形术后再狭窄中的应用

血管成形术后再狭窄是当前心血管领域的研究热点,雌激素可以促进损伤血管局部的内皮化,调节血中及损伤血管局部组织纤溶酶原激活物及其抑制剂含量,抑制球囊损伤血管局部的炎症反应、平滑肌细胞的增殖和血管壁负性重构。动物实验研究及临床研究初步证实雌激素能够预防血管成形术后再狭窄,具有良好的应用前景。     

32P液体球囊血管内照射预防血管介入治疗后再狭窄的实验研究

目的观察血管内液体球囊放射治疗对血管介入治疗后再狭窄的影响，为其临床应用提供实验依据；同时通过放射治疗效应来探讨放射治疗防止再狭窄发生的可能机制。方法兔髂动脉经球囊过度扩张损伤后，一侧经３２Ｐ液体球囊血管内照射作治疗，另一侧未经治疗作对照。用计算机图像分析方法观察血管组织形态学的变化；免疫组化方法测定增殖细胞核抗原（ＰＣＮＡ）阳性细胞以了解血管内膜增殖过程。结果兔髂动脉经球囊过度扩张损伤后，血管内膜可明显增生，ＰＣＮＡ染色为强阳性；经３２Ｐ液体球囊照射后的对侧损伤髂动脉，内膜增生明显受抑，ＰＣＮＡ染色为弱阳性，外弹力板围绕面积均增加，管腔面积无明显变化。结论３２Ｐ液体球囊确可防止再狭窄的形成，其机制可能是通过抑制平滑肌细胞增殖和改善血管重塑形成。     

切割球囊成形术与经皮腔内β-射线放射疗法联合治疗冠状动脉支架内再狭窄

目的观察切割球囊成形术(CBA)与经皮冠状动脉(冠脉)内β-射线放射疗法(β-放疗)联合治疗支架内再狭窄(ISR)的疗效及其安全性.方法冠脉内支架置入术后ISR>70%的患者295例,男性205例,女性90例,平均年龄(59.76±10.83)岁,其中112例均行CBA联合β-放疗作为β-放疗组(n=112),183例单独采用CBA(89例)或普通球囊扩张成形术(94例)为对照组(n=183).弥漫性长病变ISR者回撤β-放疗导管分段照射.所有患者术前、术后即刻及术后随访期行冠脉造影,随访靶血管血运重建(TVR)和主要不良心血管事件(MACE)发生率.结果两组患者的术前及术后即刻冠脉造影结果差异无显著性.随访期(6.3±1.6) 月β-放疗组的最小管腔直径大于对照组,管腔直径狭窄百分比小于对照组,P<0.05.β-放疗组与对照组的心绞痛、心肌梗死及病死率相似(心绞痛为10%比17%,心肌梗死为1%比2%,病死率为0%比2%), 但β-放疗组的TVR和MACE明显低于对照组(TVR为5%比16%,MACE为11%比21%,P<0.05).β-放疗组28例(25%)弥漫性长病变ISR,分段照射后随访TVR和MACE无增加.结论冠脉内β-放疗和CBA相结合治疗ISR安全、有效,TVR和MACE明显降低.采用回撤β-放疗导管技术可以有效地治疗弥漫性长病变ISR.     

32P放射性球囊血管内照射预防血管成形术后再狭窄的剂量学研究

目的探讨32P液体球囊血管内照射预防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. 方法取24只大耳白兔,建立兔双侧髂动脉粥样硬化狭窄模型,随机选择一侧髂动脉血管成形术并分别给予9.1Gy、21.8Gy和33.4Gy32P液体球囊血管照射治疗,另一侧作为自身对照.术后5周行血管造影并取材进行光镜、电镜观察,增殖细胞核抗原(PCNA)、抑癌基因P53免疫组织化学染色,用计算机图像分析其组织形态学改变. 结果9.1Gy组未观察到明显的生物效应;21.8Gy组血管壁平滑肌细胞增殖和迁移明显受抑,管腔面积无明显丢失;33.4Gy组管腔重度狭窄,内膜严重增厚,中膜平滑肌明显萎缩变薄,4例血管腔内血栓形成.结论32P液体球囊在一定的吸收剂量范围内确可安全有效地防止血管成形术后再狭窄形成,其机制可能为抑制新生内膜形成和管腔面积丢失;促进平滑肌细胞凋亡以及抑制血管负性重塑.     

放射治疗预防介入治疗后血管再狭窄的地位

介入治疗后再狭窄已成为当今心血管病治疗面临的重要问题,尽管多种方法可用于再狭窄的防治,如药物涂层支架、覆膜支架、血管内放射治疗以及再次行介入治疗或冠状动脉搭桥术,但迄今为止,任何方法都不能完全预防再狭窄的发生。近年,随着血     

放射疗法在预防冠状动脉再狭窄中的作用

经皮腔内冠状动脉成形术 (PTCA)后的再狭窄问题是 90年代冠心病治疗中的一大难题 ,再狭窄的机理大致分两大类 :(1)冠脉的弹性回缩和机械性重构 ;(2 )冠状动脉内膜增生 ,包括平滑肌细胞对损伤的反应及胶原组织增生。冠状动脉内支架的应用明显改善了。PTCA后冠脉弹性回缩与机械重构所导致的管腔缩小 ,使得再狭窄率下降至 30 %左右 ,但是支架并不减轻平滑肌及胶原的增生 ,在一定程度上 ,由于冠脉内膜对支架的异物反应 ,反而加重了这种增生 [1] 。现已证实 ,放射治疗能够减轻疤痕形成、异物骨化、男性乳房发育、Crave's病的眼球突出、眼球的…     

血小板在血管成形术后再狭窄中的作用

血管损伤后血小板广泛活化粘附、聚集和分泌，通过释放生长因子和细胞表面粘附分子的表达，可能在血管损伤反应中具有关键作用。诱导强而持久的血小板缺乏或阻断α２ｂβ３受体均可降低动物动脉球囊损伤后内膜过度增生和再狭窄的发生率，但临床试验未见任何疗效，且血小板缺乏在临床上是不实际的。新型抗α２ｂβ３单克隆抗体ａｂｃｉｘｉｍａｂ可使冠脉成形术后临床再狭窄率降低２６％，该单抗与αｖβ３呈完全交叉反应，后者可能为ａｂｃｉｘｉｍａｂ防止再狭窄的机制。     

血管内放射治疗对血管成形术后再狭窄及核因子-кB活性的影响

目的:观察32P液体球囊血管近距离照射预防血管成形术后再狭窄的量效关系及其对核转录因子核因子-кB (NF-кB)活性的影响,以探讨其防治再狭窄的可能作用机制.方法:24只大耳白兔,建立兔双侧髂动脉粥样硬化狭窄模型,随机选择一侧髂动脉血管成形术并分别给予9.1Gy组、21.8Gy组和33.4Gy 组32P液体球囊血管照射治疗(每组n=8),另一侧髂动脉灌注造影剂,作为自身对照(对照组,n=24).术后5周行血管造影并取材进行光镜观察、NF-кB、胰岛素样生长因子-1(IGF-1)免疫组织化学染色,用计算机图像分析测量新生内膜面积、中膜面积、管腔面积及免疫组化染色阳性面积百分比.结果:①光镜观察: 9.1Gy组:与对照组比病变无明显差异;21.8Gy组:内弹力膜完整无明显断裂;管腔轻度狭窄,新生内膜面积明显减小,内膜层泡沫样细胞及脂质沉积均不明显;中膜平滑肌呈轻度增厚, 排列轻度紊乱;33.4Gy组:内弹力膜破坏,管腔明显狭窄,内膜可见大量泡沫细胞及脂质沉积,大量炎性细胞浸润及细胞外基质不定形物质沉积,中膜平滑肌明显萎缩变薄,其中4例血管腔内可见血栓形成.②免疫组化染色:9.1Gy组:NF-кB、IGF-1蛋白表达与对照组无明显差异(P>0.05);21.8Gy组:NF-кB、IGF-1蛋白表达量中等,呈灶状散在分布于内皮细胞、平滑肌细胞及泡沫细胞,与对照组相比有明显差异(P<0.01);③33.4Gy组:NF-кB、IGF-1蛋白少量表达,呈散在性分布,明显低于9.1Gy组和21.8Gy组(P<0.01).结论:32P液体球囊在一定的吸收剂量范围内确可安全有效地防止血管成形术后再狭窄形成,其机制可能为抑制NF-кB及其靶基因的活化,从而抑制血管平滑肌细胞的增殖、迁移.     

放射性液体球囊血管内照射防治血管成形术后再狭窄的实验研究

目的　评定放射性液体球囊防治血管成形术后再狭窄的有效性、安全性和可行性,并观察其剂量效应关系,初步探讨其作用机制。方法　18只日本大耳白兔髂动脉经球囊过度扩张损伤后,一侧行32P或90Y放射性液体球囊血管内照射作治疗,另一侧以假源（充盈造影剂的液体球囊）未经治疗作对照。5周后重复血管造影观察血管影像学改变;原位固定取材后,分析血管断面组织形态学的变化;免疫组化方法观察增殖细胞核抗原（PCNA）阳性细胞以了解血管壁细胞的增殖情况;行胶原染色显示细胞外基质的合成情况。结果　造影可见兔髂动脉经球囊过度扩张损伤后未经治疗的靶血管段明显狭窄,平均狭窄程度达77%;血管壁吸收剂量为24Gy的靶血管段无明显狭窄或仅轻度狭窄(平均狭窄程度为12%),16Gy者为30%,8Gy者为76%。兔髂动脉病理切片行HE染色和弹力纤维染色,经计算机图像分析可见血管壁吸收剂量为24Gy和16Gy的靶血管段外弹力板围绕面积,内弹力板围绕面积,新生内膜面积,管腔面积分别与其自身对照相比具有统计学意义（P＜0.01）;8Gy者与其自身对照血管段相比无统计学意义（P＞0.05）。行PCNA染色可见对照血管段,血管壁吸收剂量为8Gy、16Gy及24Gy血管段PCNA阳性细胞百分率分别为(84±5)%、(77±3)%、(44±5)%和(21±6)%,除对照血管段和8Gy血管段之间差异无显著性(P＞0.05)外,其余各组间差异均有非常显著性（P＜0.01）,且存在剂量效应关系。未发现与放射治疗相关的不良病理改变。结论　放射性液体球囊在一定的吸收剂量范围内确可安全有效地防治血管成形术后再狭窄的形成,表现为抑制新生内膜形成和管腔面积丢失,且存在一定的剂量效应关系;其作用机制可能是通过抑制血管壁过度扩张后细胞的增殖,分泌功能和改善血管重塑形成。     

^32P放射性球囊血管内照射预防血管成形术后再狭窄的剂量学研究

目的：探讨^32P液体球囊血管内照射预防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：取24只大耳白兔,建立兔双侧髂动脉粥样硬化狭窄模型,随机选择一侧髂动脉血管成形术并分别给予9．1Gy、21．8Gy和33．4Gy ^32P液体球囊血管照射治疗,另一侧作为自身对照。术后5周行血管造影并取材进行光镜、电镜观察,增殖细胞核抗原(PCNA)、抑癌基因P53免疫组织化学染色,用计算机图像分析其组织形态学改变。结果：9．1Gy组未观察到明显的生物效应;21．8Gy组血管壁平滑肌细胞增殖和迁移明显受抑,管腔面积无明显丢失;33．4Gy组管腔重度狭窄,内膜严重增厚,中膜平滑肌明显萎缩变薄,4例血管腔内血栓形成。结论：^32P液体球囊在一定的吸收剂量范围内确可安全有效地防止血管成形术后再狭窄形成,其机制可能为抑制新生内膜形成和管腔面积丢失;促进平滑肌细胞凋亡以及抑制血管负性重塑。     

经皮腔内β-射线放射疗法与切割球囊成形术联合治疗冠状动脉支架内再狭窄

目的　旨在研究经皮冠状动脉 (冠脉 )内 β 射线放射疗法 (β 放疗 ,Novoste)与切割球囊成形术 (CBA)联合治疗支架内再狭窄 (ISR)的疗效及其安全性。方法　冠脉内支架置入术后ISR >70 %的病人 2 95例 [男性 2 0 5例 ,女性 90例 ,年龄 (5 9 76± 10 83)岁 ],其中 112例均行CBA联合 β 放疗为 β 放疗组 (n =112 ) ,183例单独采用CBA(89例 )或普通球囊扩张成形术 (94例 )为对照组 (n =183)。弥漫性长病变ISR者β 放疗先照射病变远段 ,再回撤导管照射病变近段。所有病例术前、术后即刻及术后随访期行冠脉造影 ,分析病变长度、最小管腔直径 (MLD)、参照管腔直径 (RLD)和管腔直径狭窄百分比 (DS)。随访靶血管再次成形率 (TVR)和主要不良心血管事件 (MACE)发生率。结果　术前及术后即刻两组病人的冠脉造影结果差异无显著性。随访期 (6 3± 1 6月 ) β 放疗组的MLD大于对照组 ,DS小于对照组 ,P <0 0 5。β 放疗组与对照组的心绞痛、心肌梗死及死亡率相似 ,差异无显著性(心绞痛为 10 %vs17% ,心肌梗死为 1%vs 2 % ,死亡率为 0 %vs2 % ) ,但β 放疗组的TVR和MACE明显低于对照组 (TVR为 5 %vs 16 % ,MACE为 10 %vs 2 5 % ,P <0 0 5 )。β 放疗组 2 8例 (2 6 % ,2 8 10 6 )弥漫性长病变ISR ,回撤 β 放疗导管分     

Enhanced level of micronuclei in peripheral blood lymphocytes of patients treated for restenosis with P endovascular brachytherapy

BACKGROUND: Restenosis is the complete occlusion of the blood vessel leading to such complications as ischemia/angina, myocardial infarction, and death. It can be managed by endovascular brachytherapy with both gamma and beta sources. Endovascular brachytherapy is performed worldwide on several thousands of cases per year. The gamma-emitter 192Ir as well as the beta-emitters 32P and 90Sr are mainly used. The dose to the occluded endothelial wall is 20 Gy. Interestingly, no information with respect to the dose absorbed by the blood during the course of the treatment exists. The aim of the present investigation was to verify if the micronucleus test is suitable to detect the dose absorbed by lymphocytes in the course of endovascular brachytherapy with 32P. MATERIALS AND METHODS: Blood was drawn from 16 patients immediately before and 1 day after the treatment. Frequencies of micronuclei were assessed. In order to ensure that the micronuclei did not arise due to fluoroscopy or reperfusion, we analyzed lymphocytes of 16 control patients who underwent interventional cardiology with balloon angioplasty only. RESULTS AND CONCLUSIONS: Enhanced frequencies of micronuclei were observed in lymphocytes of some donors following brachytherapy. No correlation could be detected between the level of induced micronuclei and the absorbed dose. Also, no effect of fluoroscopy or reperfusion was seen. Thus, although brachytherapy of restenosis with 32P leads to weak enhancement of the micronucleus frequency in lymphocytes, the effect was not seen in all patients; the reason for this heterogeneous response remains to be elucidated.     

Treatment of in-stent restenosis using a paclitaxel-eluting stent: acute results and long-term follow-up of a matched-pair comparison with intracoronary {beta}-radiation therapy

Aims Intracoronary radiation therapy (ICR) has significantlyimproved the long-term outcome after treatment of diffuse in-stentrestenosis (ISR). The efficacy of drug eluting stents in thissetting remains less well defined. This matched-pair analysiscompared the procedural and long-term clinical and angiographicoutcome after treatment of diffuse ISR using a paclitaxel-elutingstent (PES) with intracoronary ß-radiation therapy. Methods and Results Twenty-two patients receiving 25 PES (ACHIEVE^TM,Cook, 3.1 µg paclitaxel per square millimeter, non-polymerbased coating) for ISR underwent 6-month angiographic and 12-monthclinical follow-up. From a database including 141 patients (174lesions) undergoing intracoronary ß-radiation forISR, 25 lesions (25 patients) were pair-matched with the formergroup for lesion length and vessel size. PES implantation andICR were successfull in all patients with a significantly lowerpostprocedural in-stent diameter stenosis in the PES group (8±12%vs. 18±8%, ). Angiographic binary in-lesion restenosis at 6 month was 20% (5/25 lesions) in thePES group and 16% (4/25) in the ICR group (). PES implantation resulted in significantly higher in-stent MLDat FU (2.10±0.71 vs. 1.75±0.36, ) and a higher in-stent net gain (PES: 1.19±0.69, ICR:0.84±0.49, ). Two patients in the PES group and 6 patients in the ICR group experienced a targetlesion revascularisation at 12-month follow-up (). Conclusion Implantation of a non-polymer based paclitaxel-elutionstent and conventional ICR therapy for complex ISR lead to comparableacute and long-term clinical and angiographic follow-up results.     

Estimation of radiation dose received during treatment of in-stent restenosis using ionizing radiation

BACKGROUND: Angioplasty is a widely accepted procedure for the treatment of coronary artery disease. However, restenosis of the treated vessel occurs in 30% of patients within 6 months. Intravascular brachytherapy (IVB) is used to inhibit the formation of new tissue growth at the vessel treatment site. IVB protocols using either gamma ray or beta particle emitting isotopes have been tested and approved. However, very little data are available on resultant whole-body dose and the potential for long-term radiation effects. METHODS: Using thermoluminescence dosimetry (TLD) devices, specifically lithium fluoride (LiF) doped with Mg, Cu, and P, the radiation dose on the surface of patients undergoing IVB was measured. The TLDs were positioned on the body to obtain a measure of the gamma dose at selected anatomic locations. Additionally, the skin dose from fluoroscopy was estimated. RESULTS: Measurements indicate that the average body dose on the skin surface from all TLDs, clinical requirements, and gamma source configurations varies from 0.95 mSv (95 mrem) at the head to 27.06 mSv (2706 mrem) at the sternal notch. For beta sources, the dose varied from 0.11 mSv (11.4 mrem) at the head to 0.49 mSv (49.5 mrem) at the sternal notch. The fluoroscopy contribution of dose to the body dose (15-min exposure time) was 0.10 mSv (10 mrem) at the head and 2.57 mSv (257 mrem) to the sternal notch. CONCLUSIONS: The results suggest that surface skin exposures from gamma sources used in IVB pose acceptable risks considering the medical benefits of the procedures.     

Beta endovascular brachytherapy using CO2-filled centering catheter for treatment of recurrent superficial femoropopliteal artery disease

BackgroundRecurrent disease (restenosis) after endovascular treatment of the superficial femoral artery (SFA) remains a major problem. We evaluated the efficacy of beta-endovascular brachytherapy using the CORONA centering catheter in patients with SFA restenosis in a single-arm Phase II trial.Methods and resultsA total of 28 patients (mean age 70 years; 16 female, 12 male) with recurrent SFA stenosis were treated, and in-stent restenosis was present in 17 patients (61%). Brachytherapy was performed with strontium-90 beta source using a 7-French CO₂-filled one-segment centering catheter. New stents had to be applied in two cases. Mean interventional length was 129 mm (range 20–240 mm). A dose of 14 Gy in vessel radius (postinterventional) plus 2 mm was applied in 24 patients and 18.4 Gy in four patients. Treatment time was 7 min 32 s per radiation segment. No major adverse events occurred. Patients were followed by ankle-brachial index and duplex sonography for a median of 42 months. Cumulative restenosis rates at 1, 2, and 3 years were 9%, 28%, and 40%, respectively. Target vessel revascularization was performed in seven cases (25%).ConclusionsIn comparison to literature data, the treatment of SFA restenosis with beta brachytherapy may improve long-term patency.     

Bivalirudin compared with IIb/IIIa inhibitors in patients with in-stent restenosis undergoing intracoronary brachytherapy

BACKGROUND: Bivalirudin is replacing heparin in percutaneous coronary interventions (PCIs), including vascular brachytherapy (VBT). The aim of the study was to compare bivalirudin with eptifibatide in patients with in-stent restenosis (ISR) undergoing PCI and VBT. METHODS: One hundred forty-four patients treated with bivalirudin as a single antithrombotic agent were compared with 150 patients treated with eptifibatide. Bivalirudin as a bolus of 0.75 mg/kg followed by 1.75 mg/kg/h infusion until the end of the procedure, and eptifibatide as a double bolus of 180 microg/kg followed by 2 microg/kg/min infusion for 18 h after the procedure were used. The main outcome measures were in-hospital events and 30-day clinical outcomes. RESULTS: Baseline clinical characteristics were similar except that patients in the eptifibatide group were younger (P=.02) and had more saphenous vein graft lesions (P<.001). Patients in the bivalirudin group had a higher number of lesions in the right coronary artery (P<.001) and a higher number of vessels treated (P<.001). Postprocedure creatinine phosphokinase (CPK)-MB levels were significantly lower in the bivalirudin group (P<.03). In-hospital events showed significantly less minor bleeding (P=.01) and a trend toward lower major bleeding and major adverse cardiac events (MACE) in the bivalirudin group (P=.06). Thirty-day outcomes showed a significantly lower incidence of non-Q-wave myocardial infarction (MI) in the bivalirudin group (P=.004). CONCLUSION: Bivalirudin, as a single antithrombotic agent during PCI and VBT, is associated with significantly lower postprocedural CPK-MB elevation, minor bleeding complications, 30-day non-Q-wave MI rates, and a trend toward lower major bleeding and in-hospital MACE when compared with eptifibatide.     

钾防治血管成形术后再狭窄的临床研究

目的 观察钾在临床上预防PTCA术后再狭窄的安全性的有效性。方法 80例PTCA患随机分为对照组（40例）用常规治疗；治疗组（40例）常规治疗加钾缓释片（Slow-K)1.2g,q8h,于术前3d开始服药至术后6个月。将两组的多项观察指标进行比较分析。结果 77例完成随访，治疗组平均能提高血钾浓度0.3mmol/L，血Na^ 、Cl^-、Ca^2 、Mg^2 水平两组间无显性差异；可疑心绞痛和心肌缺血于对照组有14例（28.9%)，而治疗组仅有7例（17.9%）；冠脉造影随访对照组21例中有11例出现再狭窄，而治疗组17例中有6例；随访期间对照组有23.7%；治疗组有10.2%需再次进行血管重建术（包括PTCA和CABC），但两组比较P=0.116。结论 钾剂治疗初步显示：PTCA术后心肌缺血再发率、冠脉造影再狭窄例数以及因再狭窄需要再次行血管重建术例数，治疗组较对照组有减少趋势。     

103 Pd支架预防支架内再狭窄的量效及机制

目的　探讨1 0 3Pd支架对血管成形术后再狭窄的预防作用的量效关系及其机制。方法　5 0只雄性新西兰白兔随机分为普通支架组和各剂量的核素支架组 (8只 组 )。支架置入术后 8周行腹主动脉血管内超声和造影检查、行免疫组化染色并检测细胞凋亡。结果　在核素支架组 ,随剂量增加 ,支架段最小内径和支架内管腔面积均增大而狭窄程度减小。核素支架各组增殖细胞核抗原(PCNA)阳性细胞率均显著小于普通支架组 ,而凋亡指数除 5Gy组外均显著大于普通支架组。结论　1 0 3　Pd支架可抑制支架内血管内膜的增生 ,减少支架内狭窄的程度 ,显示出量效关系。1 0 3Pd支架既抑制血管平滑肌细胞 (VSMC)增生也诱导细胞凋亡。