颈动脉粥样硬化性狭窄患者血管内皮生长因子检测及意义

目的探讨颈动脉粥样硬化性狭窄(CAS)患者血管内皮生长因子(VEGF)水平变化。方法用酶联免疫法测定73例颈动脉粥样硬化性狭窄(CAS)患者和40例正常对照组血清中VEGF的水平。结果CAS组VEGF水平均高于正常对照组(P<0.05)。结论颈动脉粥样硬化性狭窄患者的血清VEGF水平明显升高。血清VEGF高水平可能成为CAS出现及以后发展为缺血性脑卒中的预测因素和危险因素之一。     

脑梗死患者血清ESM-1表达水平与颈动脉粥样硬化性狭窄的关系

目的 探讨脑梗死患者血清ESM-1表达水平与颈动脉狭窄关系。方法 选取79例CI患者作为CI组,49例无(CI)患者为无脑梗死组,根据颈动脉粥样硬化性狭窄程度将受试者分为4个亚组,比较各亚组间血清ESM-1水平差异有统计学意义。结果 随着颈动脉粥样硬化性狭窄程度的逐渐增加,血清ESM-1表达水平也随之逐渐升高。结论 血清ESM-1表达水平与颈动脉粥样硬化性狭窄程度存在正相关性。     

颈动脉内膜剥脱术60例临床分析

目的总结颈动脉内膜剥脱术(carotid endarterectomy,CEA)治疗有症状颈动脉粥样硬化性狭窄的疗效及并发症。方法回顾性分析60例应用CEA治疗颈动脉粥样硬化性狭窄病人的临床资料,探讨手术适应证、疗效及手术并发症的预防。结果手术效果良好57例,术区血肿行再次手术清除1例,对侧脑梗死偏瘫1例。1例死于术后急性肾功能衰竭。随访6个月复查CTA,5例出现再狭窄。结论 CEA治疗颈动脉粥样硬化性狭窄是一种简单、安全的方法,个体化围手术期处理可以降低高危病人的病死率。     

颈动脉内膜剥脱术和颈动脉支架的疗效分析

目的回顾分析颈动脉内膜剥脱(carotid endarterectomy,CEA)及颈动脉支架(carotid artery stenting,CAS)治疗颈动脉粥样硬化性狭窄的近期和中期临床效果。方法比较北京协和医院血管外科2010年1月-2014年12月行CEA及CAS患者的临床资料,分析两种术式的安全性及1年内出现再狭窄及再发卒中的情况。结果研究期间共收治颈动脉粥样硬化性狭窄患者572例,其中456例行CEA,116例行CAS。两组患者术前一般资料、临床症状、伴随疾病等因素均无显著性差异。CEA组和CAS组手术相关死亡(0.2%vs 0)、术后30 d内缺血性卒中(1.1%vs 1.7%)、急性心肌梗死(0.7%vs 1.7%)、局部血肿(0.4%vs 0.8%)、植入物感染(0.4%vs 0)、颅外神经损伤(1.1%vs 0)、过度灌注发生率(5.7%vs 3.4%)均无显著差异。CAS组术后持续低血压发生率显著高于CEA组(12.9%vs 1.1%,P0.01)。1年随访结果显示,CAS组出现治疗侧颈动脉再狭窄(﹥50%)显著高于CEA组(6.9%vs 2.6%,P=0.026),但两组术后重度狭窄(﹥70%)(2.5%vs 1.1%)及同侧卒中发生率(0.9%vs 0.4%)上没有显著性差异。结论 CEA和CAS都是治疗颈动脉粥样硬化性狭窄安全有效的措施,但CAS组术后持续低血压及治疗侧颈动脉1年再狭窄发生率高于CEA组。     

颈动脉粥样硬化性狭窄的介入干预研究

目的探讨颈动脉粥样硬化性狭窄支架介入治疗方法,评价颈动脉支架血管成形术的临床疗效及临床应用价值。方法选择2010-01—2011-06经血管造影颈动脉狭窄且符合入选标准患者80例,分为2组,Ⅰ组40例为内科药物治疗,Ⅱ组为内科治疗+介入治疗,其中Ⅱ组40例患者符合颈动脉粥样硬化病变支架治疗指征。观察2组患者治疗前后的颈动脉内膜中层厚度(IMT)、斑块数目、血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)各项指标,并记录2组患者总有效率。结果治疗6个月后,2组患者TC、TG和LDL-C水平均较治疗前明显下降,HDL-C水平较治疗前明显上升(P<0.05);Ⅱ组下降或上升的幅度较Ⅰ组更明显(P<0.05);Ⅱ组斑块面积和IMT均较治疗前明显减小(P<0.05);而Ⅰ组治疗前后斑块面积和IMT无明显变化(P>0.05);治疗后Ⅱ组斑块面积和IMT较Ⅰ组明显减少(P<0.05)。结论血管内支架成形术是治疗颈动脉粥样硬化性狭窄安全而有效的方法,比单纯内科治疗疗效明显。     

MSCTA及DSA对模型兔颈动脉狭窄的评价

目的 探讨多层螺旋CT血管造影术(MSCTA)及数字减影血管造影术(DSA)对粥样硬化性颈动脉狭窄模型兔的诊断价值.方法 30只兔中的10只做为空白对照组,余20只兔颈动脉外膜置人改良的硅胶橡胶圈后,给予兔高胆固醇饲料喂养2周诱导颈动脉狭窄模型兔,采用股动脉插管方法行MSCTA及DSA检查,观察模型兔颈动脉狭窄程度及影像学征像,比较二者对颈动脉粥样硬化性狭窄的诊断价值.结果 MSCTA及DSA均可显示颈动脉管腔狭窄的部位、范围、程度及形态以及颈动脉的血管走向,MSCTA对颈动脉狭窄敏感程度较高,但对颈动脉狭窄的特异性诊断不如DSA.结论 MSCTA和DSA能较好的反应模型兔的颈动脉狭窄部位、形态.     

胰岛素受体底物-2的Gly1057Asp基因多态性与颈动脉粥样硬化性狭窄相关性的研究

目的 探讨胰岛素受体底物-2的Gly1057Asp基因多态性与颈动脉粥样硬化性狭窄的相关性。方法 选择96例行颈部血管彩超示颈动脉狭窄≥50%的北方汉族人为实验组以及同期79例体检健康者作为对照组,通过聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术检测所有入选患者的Gly1057Asp基因多态性,比较2组的等位基因频率、基因型频率以及Gly1057Asp基因多态性对颈动脉狭窄的影响。结果 实验组中G等位基因频率(78.6%)明显高于对照组(68.4%)(P<0.05); 实验组中G/A+A/A基因型频率(36.5%)明显低于对照组(51.9%)(P<0.05)。携带等位基因G的个体患有颈动脉粥样硬化性狭窄的风险是非等位基因G携带者的1.99倍(OR=1.994,95%CI=1.068～3.761)。结论 胰岛素受体底物-2的Gly1057Asp基因多态性可能与颈动脉粥样硬化性狭窄有关,等位基因G可能是颈动脉粥样硬化性狭窄的独立危险因素。     

颈动脉粥样硬化性缺血性卒中患者外周血辅助性T细胞1、2和17分布特点研究

目的探讨颈动脉粥样硬化性缺血性卒中患者外周血辅助性T细胞1、2和17(Th1、Th2和Th17)的分布特点。方法共180例颈动脉粥样硬化性缺血性卒中患者,根据颈动脉狭窄程度分为颈动脉轻度狭窄亚组、中度狭窄亚组和重度狭窄亚组(各60例),流式细胞术检测患者外周血Th1、Th2和Th17细胞比例。结果缺血性卒中组患者外周血Th1和Th17细胞比例均高于对照组[(5.76±1.81)%对(3.54±0.29)%,P=0.000;(0.36±0.13)%对(0.18±0.03)%,P=0.000]。颈动脉狭窄不同程度亚组患者外周血Th1[(4.56±0.55)%、(4.88±0.42)%和(7.83±1.69)%,P=0.000]和Th17[(0.23±0.04)%、(0.34±0.02)%和(0.50±0.09)%,P=0.000]细胞比例差异均有统计学意义,其中,重度狭窄亚组Th1(P=0.001,0.001)和Th17(P=0.000,0.001)细胞比例高于轻度狭窄亚组和中度狭窄亚组,中度狭窄亚组仅Th17细胞比例高于轻度狭窄亚组(P=0.000)。结论 Th1和Th17细胞与颈动脉粥样硬化狭窄程度密切相关,随着颈动脉狭窄程度的加重,外周血Th17细胞比例升高,表明细胞免疫机制参与颈动脉粥样硬化的发生与发展,为颈动脉粥样硬化性缺血性卒中的免疫治疗提供理论依据。     

颈动脉内膜剥脱术治疗颈动脉狭窄

<正>颈动脉粥样硬化斑块造成的血管狭窄及闭塞是缺血性脑卒中的重要原因之一。颈动脉内膜剥脱术(carotid endarterectomy,CEA)被证实是治疗颈动脉粥样硬化性狭窄的有效方法。2012年3月至7月,我科对16例颈动脉粥样硬化性狭窄患者施行颈动膜内膜剥脱术,术后疗效较好,现总结报告如下:一、对象与方法 1.一般资料:本组男9例,女7例;年龄46~72岁,平均58岁。     

颈动脉内膜剥脱术24例临床分析

目的 探讨颈动脉内膜剥脱术治疗颈动脉粥样硬化性狭窄的疗效.方法 分析我院2009-06～2010-06手术治疗的24例颈动脉粥样硬化性狭窄患者的临床资料,探讨手术适应证、手术要点及手术并发症的预防.所有患者明确颈动脉狭窄70％～99％.术中放置转流管,常规应用补片修复成形,常规使用肝素抗凝.结果 本组中无严重的并发症发...     

Dissolution of emboli in rats with experimental cerebral thromboembolism by recombinant human tissue plasminogen activator (TD-2061)

Tissue plasminogen activator (t-PA) is frequently administered clinically as thrombolytic therapy. We injected recombinant t-PA into rats with cerebral 125I-labeled blood clot emboli to evaluate the dissolutive effect of recombinant human single-chain t-PA (rt-PA; TD-2061) on such emboli and to examine the possibility of improving neurological damage in patients with cerebral thrombosis. When rt-PA was given intravenously at a dose of 350,000 IU/kg 2 minutes before embolization, radioactivity in the affected cerebral hemisphere decreased to 20% of that in the vehicle control 2 hours after embolization. A significant decrease in radioactivity in the cerebral hemisphere was also found on the administration of 700,000 IU/kg of rt-PA 30 or 60 minutes after embolization, but not when rt-PA was administered 2 minutes after embolization. Marked inhibition of abnormal behavior such as hemiplegia was seen on treatment with rt-PA 2 minutes before embolization, but not at all when rt-PA treatment was given 30 or 60 minutes after embolization. The findings suggest that rt-PA can dissolve blood clot emboli in cerebral vessels and that prompt thrombolytic therapy is important to minimize neurological dysfunction in cases of cerebral thromboembolism.     

Demonstration of Significant Resolution of Cerebral Sino-Venous Thrombosis Associated with Intravenous Recombinant Tissue Plasminogen Activator

BACKGROUND: Cerebral sino-venous thrombosis (CVT) is commonly treated with anticoagulant therapy. There are reports of response to endovascular thrombolysis with or without mechanical aspiration in patients with clinical deterioration. CASE: We present a 29-year-old man with acute onset of severe headache, found to have extensive CVT by magnetic resonance venography (MRV). His atypical presentation led to cerebral angiography that was complicated by global aphasia and right hemiparesis from left middle cerebral artery distribution ischemia. He received intravenous rt-PA (recombinant tissue plasminogen activator) within an hour of the procedure followed, 24 hours later, by intravenous heparin infusion with significant clinical improvement. The headache severity and CVT, on follow-up MRV, resolved significantly within 2 days. CONCLUSIONS: We demonstrate clinical and neuroimaging response to systemic rt-PA in CVT. Thrombolysis may have a role in CVT management with an extended therapeutic window.     

Thrombolysis for intraventricular hemorrhage after endovascular aneurysmal coiling

Objective and Importance: Current applications of lytic therapy for intraventricular hemorrhage (IVH) rely on exclusion of vascular abnormalities as etiology. Its use in patients with recently coiled aneurysms remains far from considered safe. We report a patient with subara chnoid hemorrhage (SAH) and massive IVH from aneurysmal rupture, which was safely treated with intraventricular recombinant tissue plasminogen activator (rt-PA) after endovascular coiling. We also review two other similar cases reported in the literature. Clinical Presentation: A 61-year-old man presented with a ruptured anterior communicating artery aneurysm causing SAH and IVH (Hunt & Hess grade IV, Fisher grade III with IVH). During coiling of the aneurysm, extravasation of contrast was noted on fluoroscopy. Follow-up head computed tomography (CT) scan showed casted ventricles. Once in the intensive care unit, the patient progressed to coma, which did not improve with external ventricular drainage alone. Intervention: After endovascular coiling of the aneurysm, intraventricular rt-PA was administered. Isovolemic injections of 2 mg rt-PA every 12 hours were performed for a total of four doses. No clinical or radiological evidence of worsening SAH/IVH was documented. At the time of discharge, the patient was awake but requiring assistance with activities of daily living. Conclusion: We report the safe administration of intraventricular rt-PA after endovascular coiling of a ruptured cerebral aneurysm. Two other similar cases were found in the literature and are reviewed. Hindrance of aneurysmal cavity thrombosis by early administration of rt-PA (increasing the risk of rerupture) remains a widespread concern. The lack of such instances should therefore be acknowledged. We propose that inclusion of such patients in trials assessing safety/efficacy of thrombolytic theray in the treatment of patients with intracranial hemorrhage should be carefully considered.     

rt-PA静脉窦注射结合血管内技术治疗重症颅内静脉窦血栓

目的 探讨重组组织血浆纤维蛋白溶酶原激活剂(rt-PA)静脉窦注射结合机械性血栓清除治疗重症颅内静脉窦血栓的效果.方法 11例重症颅内静脉窦血栓患者,共进行血管内介入治疗15次;其中机械性血栓清除结合rt-PA静脉窦局部注射14例次,单纯机械性血栓清除1次;应用AnsioJet导管清除血栓9次,球囊血栓清除5次,微导丝1次.进行2次血管内治疗者4例,进行1次血管内治疗7例.每次血管内治疗rt-PA用量0～15 mg,平均(9.4±4.5)mg.无介入治疗并发症发生.手术均在气管插管全麻下进行,患者介入治疗前、治疗中及治疗后均进行全身肝素化治疗.结果 本组11例患者接受血管内治疗时已发生意识障碍8例,其中6例已行气管捕管,2例已发生脑疝;GCS3～12分,平均(8.3±2.7)分.恢复优良8例,死亡3例.存活病例MRI/MRV随访10-32个月(平均21个月),静脉窦通畅6例,部分通畅2例.无静脉窦血栓复发病例.结论 重症颅内静脉血柃可危及病人的生命,常规治疗疗效差.溶栓药物局部应用结合机械性血栓清除可以快速使受累的静脉窦恢复通畅,是一种安全、有效的治疗方法.     

脑白质疏松程度与急性脑梗死患者静脉溶栓治疗后症状性脑出血转化的相关性研究

目的探讨脑白质疏松(LA)程度与急性脑梗死患者静脉应用重组人组织型纤溶酶原激活剂(rt-PA)溶栓治疗后症状性脑出血(sICH)转化的相关性。方法连续选取急性颈内动脉系统脑梗死患者117例,符合溶栓治疗指征者采用静脉rt-PA以0.9 mg/kg足量溶栓治疗,其余则给予普通安慰剂治疗。所有患者根据Wahlund改良LA分级量表(ARWMC)评分对LA严重程度进行分级:轻度(1~5分),中度(6~10分),重度(10分)。溶栓后24~36 h复查头CT,判定是否出现sICH转化。比较不同程度LA患者中溶栓组和安慰剂组sICH转化率。结果本研究组中,溶栓治疗者49例,安慰剂使用者68例;LA轻度45例,LA中度25例,LA重度47例。本研究共有10例患者(8.5%)发生s ICH转化,其中溶栓治疗者7例,安慰剂使用者3例;LA轻度2例,LA中度2例,LA重度6例。在LA轻度及中度患者中,溶栓组患者sICH转化率略高于较安慰剂组(P=0.052,P=0.650)。而在LA重度患者中,溶栓组患者s ICH转化率明显高于安慰剂组(P=0.043)。Pearson相关性分析结果显示,溶栓组患者ARWMC评分与其静脉溶栓治疗后sICH转化率呈正相关(r=0.476,P=0.0005)。结论重度LA可增加急性脑梗死患者rt-PA静脉溶栓后sICH转化的风险。了解患者的LA程度有助于对临床溶栓决策的选择和对患者预后的判断。     

Stroke in ovarian hyperstimulation syndrome in early pregnancy treated with intra-arterial rt-PA

Ovarian hyperstimulation syndrome (OHSS) caused by fertility medications can predispose women to thrombosis. The authors present a case of a previously healthy woman who underwent in vitro fertilization and experienced a middle cerebral artery thrombosis that was subsequently lysed with intra-arterial recombinant tissue plasminogen activator (rt-PA). To the authors' knowledge, this is the first reported case of successful use of rt-PA to lyse a cerebral arterial thrombus resulting from severe OHSS. The patient made a near complete neurologic recovery and delivered a healthy infant at term, illustrating that intra-arterial thrombolysis can be used with relative safety even in very early pregnancy.     

Does clinical-CT 'mismatch' predict early response to treatment with recombinant tissue plasminogen activator?

BACKGROUND: We hypothesized that patients with clinically severe strokes but less severe early ischemic changes on brain CT (i.e., clinical-CT mismatch) may respond better to intravenous recombinant tissue plasminogen activator (i.v. rt-PA) within 3 h of symptom onset. METHODS: In this secondary analysis of the CLOTBUST data, patients with middle cerebral artery occlusions on transcranial Doppler (TCD) were treated with i.v. rt-PA. Alberta Stroke Program Early CT Scores were obtained with raters blinded to the NIH Stroke Scale and TCD results. Two mismatch criteria and three criteria of response to therapy were explored. RESULTS: Of 126 patients, 67% had a mismatch type 1 and 74% had a mismatch type 2. The presence of clinical-CT mismatch by either definition did not correlate with any of the three criteria of response to rt-PA. Recanalization was a strong determinant of response, whether or not mismatch was present. CONCLUSIONS: Mismatch between severity of neurological deficit and CT findings is common but does not predict response to rt-PA therapy given within 3 h.     

The thrombolytic effect of miniplasmin in a canine model of femoral artery thrombosis

BACKGROUND AND PURPOSE: Miniplasmin was a des-kringle variant of plasminogen with potential pharmacological application. We investigated the thrombolytic effect of miniplasmin in a canine model of femoral artery thrombosis. METHODS: In anesthetized dogs, a stable occlusive thrombus was formed by mechanical and electrolytic injury of the vessel wall, that the animals were later injected with miniplasmin (0.75 mg/kg, 1.5 mg/kg and 3.0 mg/kg, i.a.) and rt-PA (0.5 mg/kg, i.a.) intra-arterially. Hemodynamic parameters and hemorrhage status were monitored for 2 h. Thrombin time, activated partial thromboplastin time, prothrombin time and fibrinogen concentration were tested at 2 h after administration. Fibrin degradation product and D-dimer concentration were tested by ELISA. RESULTS: The incidence of reperfusion in the miniplasmin (3.0 and 1.5 mg/kg) groups was 100%, and time to reperfusion was (3.3+/-1.0) and (7.0+/-2.3) min, which was shorter than rt-PA. After reperfusion, none of the vessels in the miniplasmin (1.5 and 3.0 mg/kg) groups reoccluded, whereas 20% of vessels reoccluded in the rt-PA group. Rudimental thrombus mass in the miniplasmin (1.5 and 3.0 mg/kg) groups were smaller than rt-PA. The operative wounds in all miniplasmin groups had no hemorrhage within 2 h. There were no significant differences in thrombin time, activated partial thromboplastin time and prothrombin time. Fibrinogen concentration in the miniplasmin (3.0 mg/kg) group reduced significantly as compared with baseline and thrombosis values, whereas these values in the miniplasmin (1.5 and 0.75 mg/kg) groups were unchanged. Fibrin degradation product and D-dimer concentration increased significantly after thrombolysis. CONCLUSIONS: The results suggest that miniplasmin may be useful for the treatment of thrombosis and without complication of hemorrhage. This is in contrast to rt-PA, which intrinsically has a higher risk of occurring the hemorrhage risk.     

Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model

INTRODUCTION: Thrombolytics such as recombinant tissue plasminogen activator (rt-PA) have advanced the treatment of ischemic stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism. OBJECTIVE: To improve the efficacy of this thrombolytic therapy, the synergistic effect of rt-PA and 120 kHz or 1.0 MHz ultrasound was assessed in vitro using a porcine clot model. MATERIALS AND METHODS: Fully retracted whole blood clots prepared from fresh porcine blood were employed to compare rt-PA thrombolytic treatment with and without exposure to 120-kHz or 1-MHz ultrasound. For sham studies (without ultrasound), clot mass loss was measured as a function of rt-PA concentration from 0.003 to 0.107 mg/ml. For combined ultrasound and rt-PA treatments, peak-to-peak pressure amplitudes of 0.35, 0.70 or 1.0 MPa were employed. The range of duty cycles varied from 10% to 100% (continuous wave) and the pulse repetition frequency was fixed at 1.7 KHz. RESULTS: For rt-PA alone, the mass loss increased monotonically as a function of rt-PA concentration up to approximately 0.050 mg/ml. With ultrasound and rt-PA exposure, clot mass loss increased by as much as 104% over rt-PA alone. Ultrasound without the presence of rt-PA did not significantly enhance thrombolysis compared to control treatment. The ultrasound-mediated clot mass loss enhancement increased with the square root of the overall treatment duration. CONCLUSIONS: Both 120-kHz and 1-MHz pulsed and CW ultrasound enhanced rt-PA thrombolysis in a porcine whole blood clot model in vitro. No clear dependence of the observed thrombolytic enhancement on ultrasound duty cycle was evident. The lack of duty cycle dependence suggests a more complex mechanism that could not be sustained by merely increasing the pulse duration.     

Absence of potentiation with murine antiplatelet GPIIb/IIIa antibody of thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in a canine venous thrombosis model

F(ab')2 fragments of a murine monoclonal anti-platelet GPIIb/IIIa antibody (7E3) are a potent platelet aggregation inhibitor, which in a canine coronary artery thrombosis model accelerate lysis with recombinant tissue-type plasminogen activator (rt-PA) and prevent reocclusion (7). In the present study, we have investigated the potential value of platelet aggregation inhibition as adjunctive therapy to lysis of venous thrombi, by measuring the thrombolytic potency of 7E3-F(ab')2 and rt-PA used alone or in combination, in dogs with a 125I-fibrin labeled femoral vein thrombus. The dose-response of thrombolysis with rt-PA infused over 4 hours was linear: doses of 0.075 mg/kg, 0.15 mg/kg and 0.3 mg/kg produced 37 +/- 3, 57 +/- 11 and 83 +/- 4% lysis respectively, against a background value of 20 +/- 2%. With F(ab')2 fragments of 7E3 given as a bolus of 1.2 mg/kg, which saturated 70% of the platelet GPIIb/IIIa receptors and prolonged the bleeding to more than 30 min, lysis was not significantly increased over background. Combination of 0.3 or 0.6 mg/kg of 7E3-F(ab')2 with either 0.03 or 0.06 mg/kg of rt-PA did not produce more lysis than obtained with a comparable dose of rt-PA alone. No significant changes in plasma fibrinogen or alpha 2-antiplasmin were observed with either agent alone or with the combination. It is concluded that extensive inhibition of platelet aggregation does not potentiate the thrombolytic effect of rt-PA in this venous thrombosis model.