重组腺病毒介导的人一氧化氮合酶基因转染对大鼠颈总动脉球囊损伤后新生内膜的影响

目的 :研究重组腺病毒介导的人内皮型一氧化氮合酶基因 (eNOS)表达生成的一氧化氮合酶 (NOS)对球囊损伤后大鼠颈总动脉新生内膜的抑制作用。方法 :在 2 93细胞内扩增、纯化Ad LacZ和Ad eNOS ,鉴定其是否携带有LacZ和eNOS基因。建立大鼠颈总动脉球囊损伤模型后 ,将磷酸缓冲液 (PBS)、Ad LacZ和Ad eNOS在体内分别转染到损伤血管段 ,以X gal染色、苏木精 伊红染色 ,免疫组化及计算机图像分析处理等方法观察转染动脉节段外源性eNOS蛋白表达及其对新生内膜的影响。结果 :重组腺病毒携带有eNOS基因 ,并且在损伤血管段得到有效表达。转染后PBS组、Ad LacZ组和Ad eNOS组的新生内膜面积分别为 (0 .187± 0 .0 18)、(0 .134± 0 .0 6 1)和 (0 .0 6 3± 0 .0 2 6 )mm 2 ,新生内膜与中膜面积比值 (I/M)分别为 1.5 76± 0 .2 73、1.342± 0 .35 7和 0 .5 6 0± 0 .16 1。与PBS组、Ad LacZ组相比Ad eNOS组无论新内膜面积 ,还是管腔狭窄程度都明显减小。结论 :腺病毒介导的eNOS基因转染能有效抑制球囊损伤后血管内膜的增生 ,可防治血管成形术后再狭窄     

Effect of antioxidant probucol for preventing stent restenosis.

Probucol is a lipid-lowering drug that has an antioxidant effect. The authors sought to investigate the effect of probucol on stent restenosis after the usual 3-day pretreatment protocol. From March 1999 to August 2000, 78 patients (mean age, 56 +/- 8; 49 male) with coronary artery disease who underwent coronary stenting were enrolled. After a diagnostic angiography was done, each eligible patient was randomized to either the probucol or the control group. Following the procedure, ticlopidine was administered for 1 month; aspirin and probucol continuously. Angiographic follow-up was done in 81% (57/70) and angiographic restenosis was not different between the two groups (21% vs. 24%; P = 0.81). In conclusion, antioxidant probucol did not show a beneficial effect on stent restenosis with 3 days of premedication protocol.     

Pimecrolimus and dual pimecrolimus-paclitaxel eluting stents decrease neointimal proliferation in a porcine model.

OBJECTIVES AND BACKGROUND: The purpose of this study was to determine the effectiveness and vascular response of a pimecrolimus drug eluting stent and a combination (pimecrolimus + paclitaxel) stent as compared with bare metal controls in the porcine coronary model. METHODS AND RESULTS: In the first phase of the study, cobalt chromium stents were loaded with an erodible polymer and either a slow release or a fast release formulation of pimecrolimus. Thirty stents (metal, n = 10; pimecrolimus slow, n = 10; pimecrolimus fast, n = 10) were implanted in the coronary arteries of 10 pigs. At 30 days, neointimal proliferation and inflammation were both significantly less in the pimecrolimus fast release group as compared with the bare metal controls. Endothelialization was complete and equal in all three groups of stents. In the second phase of the study, stents were loaded with an erodible polymer with alternating reservoirs of paclitaxel and pimecrolimus. Twenty stents (8 control stents and 12 dual stents) were implanted in the coronary arteries of seven pigs. At 30 days, neointimal proliferation was significantly less in the dual drug group as compared with the bare metal controls. Endothelialization was complete in both groups of stents, suggesting complete healing of the arteries. CONCLUSIONS: In a 30-day porcine stent model, pimecrolimus inhibits neointimal proliferation as compared with bare metal stents. Also, the proof of concept of a dual drug eluting stent was established showing both safety and efficacy.     

Kinetics of drugs delivery to the arteriall wall via polyurethane-coated removable nitinol stent: Comparative study of two drugs

Polymer-coated removable stents were used to deliver ¹⁴C-labeled etretinate and ³H-labeled forskolin to the vessel wall in 31 New Zealand White rabbits to study their kinetics. Stents loaded with etretinate (n = 8) and forskolin (n = 14) were implanted in the rabbit carotid arteries, and the animals were euthanized at different time intervals. Drug levels were measured in the media and adventitia of the stented segment, in distant tissues, and in blood. In four rabbits, forskolin-loaded stents were percutaneously retrieved 2 hr after implantation in the carotid artery, and the tissue and blood levels were determined 2 and 24 hr after retrieval. In seven rabbits etretinate-loaded stents were retrieved 72 hr after implantation in abdominal aorta, and drug levels were measured in the tissues and blood immediately after and at 1 and 4 days after retrieval. Levels of etretinate in the vessel wall peaked at 24 hr (250 ng/mg) and remained high up to 72 hr (185 ng/mg) after stent placement. Levels of forskolin peaked within 2 hr of stent placement (135 ng/mg) and rapidly declined to 4.9 ng/mg at 24 hr with the stent in situ. About 50% (1.4 mg) of the original etretinate remained in the stent at 72 hr compared to about 5% (0.08 mg) of forskolin at 24 hr. Ratio of peak drug levels in the vessel wall to those in the blood was 6,000 for etretinate and 780 for forskolin. After stent removal at 72 hr, levels of etretinate in the aortic wall declined from 74 ng/mg to 29 ng/mg at 1 day and to 14 ng/mg at 4 days. Levels of forskolin declined rapidly within 2 hr of stent removal from 134 ng/mg to 1.2 ng/mg and further to 0.12 ng/mg within 24 hr. Polymer-coated stents could be used for local drug delivery to the vessel wall. Kinetics of delivery and washout vary between drugs.     

西洛他唑在冠状动脉介入术后的应用

经皮冠状动脉介入治疗（PCI）广泛用于缺血性心脏病，其术后的再狭窄庭血栓高风险是导致心脑血管事件发生。PCI术后给予西洛他唑，具有抗血栓和扩张血管作用、抑制血管平滑肌细胞的增殖、调节血脂浓度、对抗血栓形成、减少心脑血管事件发生等应用。     

干预非糖尿病患者胰岛素抵抗对冠脉支架植入术后的影响

目的观察二甲双胍干预非糖尿病患者胰岛素抵抗（insulin resestence,IR）对冠状动脉支架植入术（percutaneous coronary intervention,PCI）后急性心血管事件以及冠脉支架再狭窄的影响。方法对97例冠状动脉病变接受PCI术并发IR的非糖尿病患者随机分成2组,一组在基础治疗的基础上加用二甲双胍片（0.5g,3次/d,口服）作为试药组,另一组仅作基础治疗为对照组,观察两组支架植入术后一年的急性心血管事件（心绞痛、心肌梗死、心因性死亡）及支架内再狭窄的发生率。结果术后1年11例失访。86例随访中,试药组（n=41）5例发生心绞痛,无心肌梗死发生,造影复查47处植入支架发现再狭窄6例,即再狭窄发生率为13%（6/47）;对照组（n=45）14例发生心绞痛,2例发生心肌梗死（ST段抬高、非ST段抬高各1例）,造影复查53例植入支架发现再狭窄10例,另有2例出现新的冠脉狭窄（病变的狭窄程度≥50%）,即再狭窄发生率为30%（16/53）。急性心血管事件和支架内再狭窄发生率试药组低于对照组（均P<0.05）。结论在非糖尿病患者伴IR行PCI术后应用二甲双胍进行干预可以降低患者的急性心血管事件以及冠脉支架再狭窄发生率。     

药物洗脱支架置入后再狭窄

尽管药物涂层支架较金属裸支架可以明显降低再狭窄率,但随着临床中的广泛应用,药物支架术后亦有10%发生支架内再狭窄,具体机制不明,主要与介入手术操作和涂层药物、支架本身等有关,多发生支架内局限性狭窄,亦有弥漫病变,最佳治疗手段尚存在争议,再次药物支架置入及血管内放射治疗等都是不错的选择。     

Long-term efficacy of percutaneous transluminal angioplasty on incidence of myocardial infarction, relief of symptoms and survival

This study was conducted to determine the long-term effects of percutaneous transluminal coronary angioplasty (PTCA) on the incidence of myocardial infarction, survival, and relief of symptoms. A total of 124 patients were included in the study and were followed for 16 to 25 months. The success rate of PTCA was 91.2% and 160 stenoses were dilated. Fifty-nine patients had multivessel disease (MVD) and 54 had single-vessel disease (SVD). There was no difference in survival when patients with SVD were compared with those with MVD. The cardiac survival rate for both groups was greater than 98%. Nine patients had myocardial infarction in the area of the dilated artery: 3 patients (5.5%) with SVD and 6 patients (10.1%) with MVD. Ninety-six patients (84.9%) remained free of symptoms: 46 patients (85.2%) with SVD and 50 patients (84.7%) with MVD. These data demonstrate the long-term efficacy of PTCA in patients with SVD and MVD with regard to control of symptom of angina, improved survival, and prevention of myocardial infarction.     

辐射防治血管成形术后再狭窄的机制研究进展

辐射治疗是防治血管成形术后再狭窄的一个新手段。然而尚存在许多问题。究其原因是机制尚未明确，本文主要从相关的细胞及细胞因子着看综述了辐射治疗防治血管成形术后再狭窄机制的研究进展。     

Factors predictive of cardiac events and restenosis after sirolimus-eluting stent implantation in small coronary arteries.

OBJECTIVES: Predictors of cardiac events and restenosis after sirolimus-eluting stent (SES) implantation in small coronary arteries were evaluated. BACKGROUND: Although SES implantation has markedly reduced the risk of restenosis, small vessel disease remains a major cause of SES failure. METHODS: We prospectively investigated the factors predictive of cardiac events and restenosis in 1,092 consecutive patients who received SES implantation for 1,269 lesions in small coronary arteries (< or = 2.8 mm). Follow-up angiography at 6 months was performed in 751 patients with 889 lesions (follow-up rate 70.3%). RESULTS: Restenosis (diameter stenosis > or = 50%) was angiographically documented in 65 patients with 77 lesions (8.7%): 55 focal (71.4%), 8 diffuse (10.4%), 2 diffuse proliferative (2.6%), and 12 total (15.6%). Lesion length, stent length, reference artery size, and in-stent restenotic lesions were univariate predictors of restenosis. By multivariate analysis, lesion length (OR 1.04; 95% CI 1.02-1.05; P < 0.001) and in-stent restenotic lesions (OR 3.38; 95% CI 1.80-6.35; P < 0.001) were significant independent predictors of restenosis. During follow-up (23.2 +/- 7.9 months), there were 17 deaths (5 cardiac and 12 noncardiac), 5 nonfatal Q-wave myocardial infarctions, and 42 target lesion revascularizations. The cumulative probability of survival without major adverse cardiac events (MACE) was (96.6 +/- 0.6)% at 1 year and (95.1 +/- 0.7)% at 2 years. In multivariate analysis, lesion length (HR 1.04; 95% CI 1.01-1.07; P = 0.004) and in-stent restenotic lesions (HR 3.29; 95% CI 1.58-6.86; P = 0.001) were independently related to MACE. CONCLUSIONS: SES implantation in small coronary arteries is safe and effective, with lesion length having a major impact on restenosis and MACE.