Short-Term and Long-Term Effects of Low-Density Lipoprotein (LDL) Apheresis on Restenosis after Percutaneous Transluminal Coronary Angioplasty (PTCA): Is Lowering Lp(a) by LDL Apheresis Effective on Restenosis after PTCA?

Abstract: It has been reported that serum lipoprotein(a) (Lp[a]) levels in patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA) were significantly higher than in patients without restenosis. In this study, we evaluated the preventive effect of LDL apheresis on restenosis after PTCA in patients with hypercholesterolemia. For 10 patients who had shown a serum cholesterol level of more than 220 mg/dl despite treatment with antihypercholesterolemic drugs, LDL apheresis was conducted every 2 weeks after a successful PTCA until restenosis could be checked. In 4 patients, LDL apheresis was conducted for 2 years. LDL apheresis significantly reduced serum cholesterol from 248 ± 22 mg/dl to 135 ± 26 mg/dl and Lp(a) from 42 ± 34 mg/dl to 21 ± 16 mg/dl. The average degree of stenosis in the 11 lesions undergoing PTCA was 92 ± 6% before PTCA, 35 ± 10% immediately after PTCA, and 38 ± 19% at 3 to 4 months after PTCA. Restenosis was observed in only 1 lesion. In 4 patients who received LDL apheresis for 2 years, restenosis did not occur in any of the 4 lesions treated. We concluded that LDL apheresis was an efficacious therapy to prevent restenosis after PTCA in patients with hypercholesterolemia.     

颅内外动脉狭窄支架植入手术前后血清胱抑素C水平变化及对动脉再狭窄的影响

目的探讨颅内外动脉狭窄支架植入手术前后血清胱抑素C(Cys-C)的水平变化及其对动脉再狭窄的影响。方法选取2008—2010年47例颅内外动脉狭窄患者进行血管内支架植入术治疗,术后6～12个月复查数字减影血管造影(DSA),分别于术前、术后3 d和复查DSA时检测患者血清Cys-C水平,并对比分析动脉再狭窄组与未狭窄组的血清Cys-C水平。结果术后6～12个月复查DSA显示,21例(44.7%)患者出现了再狭窄,其中13例再狭窄率<50%,8例再狭窄率≥50%,26例患者未发现血管明显再狭窄。再狭窄组术前及术后3 d的血清Cys-C水平分别与未狭窄组比较,差异均无统计学意义(P>0.05);再狭窄组和未狭窄组术后3 d的血清Cys-C水平与术前比较,差异均有统计学意义(P<0.05);再狭窄组术后6～12个月的血清Cys-C水平分别与术前及未狭窄组比较,差异均有统计学意义(P<0.05)。结论支架术后血清Cys-C水平的增高可能与再狭窄有关,并可能成为评价缺血性脑血管病复发的一个指标。     

覆膜支架在外周血管病变中的应用

覆膜支架在外周血管病变中主要用于各种原因引起的动脉瘤、假性动脉瘤和其他动静脉畸形,最近有人将其应用于创伤性病变和PTA、TIPS等介入操作之中,效果显著,但是术后内皮化进程较长以及较高的再狭窄率仍是困扰覆膜支架临床应用进一步发展的主要原因。     

低剂量氯吡格雷在冠状动脉再狭窄家猪模型中应用的初步探讨

目的评价低剂量氯吡格雷在冠状动脉再狭窄家猪模型中的应用效果。方法选取健康家猪6头,抽取静脉血测定ADP(Adenosine Diphosphate,二磷酸腺苷)诱导的血小板聚集率作为基础值,然后开始喂食氯吡格雷(25mg/d)和常规剂量的阿司匹林,开始给药后第4天行介入手术构建冠状动脉过度扩张再狭窄模型并行支架植入术,同时在给药后第4、8﹑14天再次抽血测定ADP诱导的血小板聚集率,评价氯吡格雷对血小板聚集率的抑制效果,记录术后压迫止血情况及术中、术后的安全性,14天时处死动物并血管取材评价支架内血栓情况。采用SPSS10.0进行统计学分析。结果家猪平均体重为(23.1±4.4)Kg,ADP诱导的血小板聚集率基础值为(43.08±5.06)%。用药后第4天,血小板聚集率值较基础值明显下降[(29.05±9.26)%:(43.08±5.06)%,P=0.008],用药后8天血小板聚集率值进一步下降,用药后14天,血小板聚集率值趋于稳定,达到并维持抗血小板聚集的效果,术中和术后24小时均未发生冠状动脉事件,14天时血管取材病理切片未见支架内血栓形成。结论在冠状动脉再狭窄家猪模型中,低剂量氯吡格雷可以达到抑制ADP诱导的血小板聚集的效果,同时低剂量氯吡格雷联合常规剂量的阿司匹林可以保证冠状动脉再狭窄家猪模型的安全性,并降低实验费用。     

冠状动脉内超声评价支架再狭窄

目的探讨冠状动脉内支架再狭窄的机制.方法50例确诊冠心病患者接受65个支架置入术,10个月后复查冠状动脉造影和血管内超声成像检查.根据冠状动脉造影结果将患者分为支架再狭窄组(26个支架)和无支架再狭窄组(39个支架),分别对其冠状动脉造影和血管内超声进行定量测量分析.同时观察支架内再狭窄的方式.结果血管内超声定量测量发现支架再狭窄组最小血管内膜腔面积和支架最小截面积[分别为(2.5±1.2)mm2和(4.2±1.8)mm2]明显小于无支架再狭窄组[分别为(5.2±1.4)mm2和(6.8±1.7)mm2](P分别＜0.001和＜0.01),但两组新生内膜截面积比较差异无显著性[分别为(1.7±1.0)mm2和(1.5±0.9)mm2,P＞O.05].支架内再狭窄以局灶性狭窄为多见(69.2%).结论支架扩张程度是决定支架内再狭窄的重要因素,而支架内内膜增生并不明显.支架内再狭窄以局灶性狭窄为多见.     

兔颈动脉球囊损伤后内膜增生的实验研究

目的　制作兔颈动脉球囊损伤后再狭窄模型 ,观察兔颈动脉球囊损伤后内膜增生的动态变化 ,探讨再狭窄的可能机制。方法　健康雄性家兔 40只 ,随机分为正常对照组 ( 10只 ) ,实验Ⅰ、Ⅱ、Ⅲ组 ,实验组行右颈总动脉血管成形术 ,并分别于术后第1、2和 4周处死实验Ⅰ、Ⅱ、Ⅲ组 ,第 4周同时处死对照组兔。光镜下观察内膜损伤后形态学变化 ,并进行图像分析。结果　与对照组比 ,实验组内膜面积呈持续性显著增加 (P <0 0 5 ,P <0 0 1) ,管腔面积从第 2周开始呈持续性显著减少 (P <0 0 1)。结论　兔颈动脉球囊损伤能较好的模拟再狭窄形成过程 ,球囊损伤后内膜增生是管腔狭窄的主要因素     

Antirestenotic Effects of a Novel Polymer-Coated D-24851 Eluting Stent. Experimental Data in a Rabbit Iliac Artery Model

Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (dl-lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 ± 0.0025 μM (31 ± 1 μg; low dose; n = 7), 0.55 ± 0.02 μM (216 ± 8 μg; high dose; n = 6), and 4.55 ± 0.1 μM (1774 ± 39 μg; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.     

冠状动脉支架术术后再狭窄与临床因素的关系

目的通过对再狭窄和临床易患因素关系的分析希望找出再狭窄的独立预测因素。方法本研究回顾性分析了60例（共67支血管）在我院成功进行了冠状动脉内支架术，并于术后6个月有完整冠状动脉造影随访资料的病人，通过单因素及多因素方法分析再狭窄与临床因素的关系。结果总再狭窄率为31．3％（21／67）。单因素分析中发现冠状动脉内支架≥3．5mm组的再狭窄率较低，和再狭窄的关系有显著统计学意义（P＜0．01）。术前吸烟、有到病变远端侧支循环、最大球囊充气压和术后最小管腔开放直径较小组的再狭窄率较高，以上4因素和再狭窄的关系有统计学意义（P＜0．05）。多元Logistic回归分析结果显示应用直径≥3．5mm冠状动脉内支架可降低再狭窄率，最大球囊充气压较大和吸烟可使再狭窄率增高。结论冠状动脉内支架直径大小、球囊最大充气压和吸烟为再狭窄的独立预测因素。     

球囊成形术后氯沙坦对兔血管内膜增殖及巨噬细胞表达的影响

目的　通过观察AT1受体的特异性拮抗剂氯沙坦 (Losartan)对兔腹主动脉球囊成形术后内膜增殖和巨噬细胞表达的影响 ,探讨氯沙坦治疗血管再狭窄的机制。方法　采用内皮剥脱加高脂饮食 (含 1 5 %胆固醇 )喂养 8周制作兔腹主动脉粥样硬化膜型 ,然后对狭窄部位行球囊成形术。术后氯沙坦组给予氯沙坦 10mg·kg-1·day-1口服 ,对照组喂生理盐水。 4周后取腹主动脉行组织形态学观察 ,用免疫组织化学方法分析巨噬细胞。结果　对照组内膜厚度 /中膜厚度比值为 0 65± 0 17,氯沙坦组则减少为0 44± 0 11(P <0 0 1) ,对照组内膜面积 /中膜面积比值为 0 74± 0 16,氯沙坦组则减少为 0 5 4± 0 13(P <0 0 1)。氯沙坦组新生内膜中巨噬细胞数亦较对照组显著减少 (P <0 0 1)。结论　氯沙坦通过抑制AngⅡ的作用进而抑制巨噬细胞的浸润 ,抑制炎症反应 ,从而减轻再狭窄     

Arterial wall injury,arterial wall healing and restenosis

Substantial damage is inflicted on the arterial wall by conventional balloon angioplasty as well as by newer interventional devices. Restenosis seems to be due to an exaggerated, albeit normal healing response of the arterial wall to interventional injury. Since the relationship between arterial wall damage and restenosis is not entirely clear, experimental studies were performed in the normal rabbit to assess the effects of the nature and the extent of injury on the subsequent myointimal proliferation. The results suggest that the myointimal proliferation is an aspecific repair response to wall injury. The results further suggest an on-off character of myointimal proliferation after injury, which would imply that alternative, less damaging interventional methods may not reduce the problem of restenosis.