蛛网膜下腔出血后血管痉挛的防治

脑血管痉挛(CVS)被认为是蛛网膜下腔出血(SAH)致死及致残的最主要原因之一[1].目前临床上最常用于治疗CVS的方法是应用钙通道阻滞剂(CEB).现在公认的用于防治SAH后CVS的CEB为尼莫地平,尚未见用西比灵预防和治疗SAH后CVS的报道,现将我们应用西比灵治疗的CVS 37例报告如下.     

尼莫地平预防创伤性蛛网膜下腔出血所致的脑血管痉挛

本文观察尼莫地平预防创伤性蛛网膜下腔出血(SAH)所致的脑血管痉挛(CVS)。将创伤性SAH病人136例分为两组,尼莫地平组(65例)于伤后24小时内给予尼莫地平治疗,对照组(71例)采用一般综合治疗各三周。结果提示尼莫地平组死亡率(24.6％)、CVS发生率(26.1％)分别低于对照组(33.8％和36.6％),说明尼莫地平预防创伤性SAH所致的CVS有效。     

尼莫地平联合阿托伐他汀钙预防蛛网膜下腔出血后脑血管痉挛

目的探讨尼莫地平加阿托伐他汀钙预防蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)中的作用和不良反应。方法 63例经临床及影像学检查确诊的SAH患者根据治疗方案的不同分为2组,对照组在SAH常规治疗基础上加用尼莫地平;观察组在SAH常规治疗基础上加用尼莫地平和阿托伐他汀钙。治疗结束后评价2组CVS发生率和不良反应。结果治疗后观察组CVS发生率8.82%(3/34),明显低于对照组的37.93%(11/29),2组比较差异有统计学意义(P<0.05)。2组不良反应均较轻,总发生率比较差异无统计学意义(P>0.05)。结论尼莫地平加阿托伐他汀钙用于预防SAH患者发生CVS疗效较好,且不良反应轻。     

不同剂量尼莫地平防治蛛网膜下腔出血后脑血管痉挛的疗效观察

目的　探讨应用尼莫地平防治蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的最佳剂量。方法对30例原发性SAH患者分别给予尼莫地平大剂量(1~2mg/h, 12例)、中剂量(0. 5~0. 8mg/h, 12例)、小剂量(0. 2~0 .4mg/h, 6例)治疗。用经颅多普勒(TCD)检测SAH患者脑动脉的收缩峰速度,观察各组CVS发生的情况。结果　大剂量组与中剂量组用药后的脑动脉血流速度相比差异无显著性(P>0. 05),大、中剂量组与小剂量组用药后的脑动脉血流速度相比差异均有显著性(P<0.05 ~0. 01);大、中剂量组治疗后与治疗前的脑动脉血流速度相比差异均有显著性(均P<0. 05),小剂量组治疗前后的脑动脉血流速度相比差异无显著性(P>0 .05)。结论　大、中剂量尼莫地平对SAH后CVS均有较好的防治作用,而小剂量尼莫地平则不能有效防治CVS。     

静滴尼莫地平并腰穿脑脊液置换术治疗SAH 24例临床观察

目的　探讨静滴尼莫地平并腰穿脑脊液置换术防治蛛网膜下腔出血 (SAH )后脑血管痉挛 (CVS)及缓解头痛的疗效。方法　将 46例SAH随机分为对照组 (2 2例 )和治疗组 (2 4例 )。对照组采用常规内科治疗 ,治疗组在常规治疗的基础上采用静滴尼莫地平并腰穿脑脊液置换术。结果　治疗组头痛持续的时间较对照组缩短 ,具有统计学意义 (P <0 0 1)。治疗组、对照组CVS的发生率分别为 12 5 %、3 7 5 % ;死亡率 12 5 %、3 6 5 % ,经统计学处理有显著性差异 (P <0 0 5 )。结论　静滴尼莫地平针并行腰穿脑脊液置换术优于常规内科治疗 ,可有效缓解SAH后头痛 ,且防治CVS安全有效     

尼莫地平在aSAH治疗中的研究进展

<正>自发性蛛网膜下腔出血(subarachnoid hemo-rrhage,SAH)主要由颅内动脉瘤破裂引起,脑血管痉挛(cerebral vasospasm,CVS)、迟发性脑缺血(delayed cerebral ischaemia,DCI)是动脉瘤性SAH(aneurysmal SAH,a SAH)致残和死亡的主要原因~([1~3])。早期、积极预防这些并发症有助于改善患者预后。Meta分析表明,尼莫地平降低aSAH患者CVS、DCI、迟发性神经缺失发生率,明显改善患者预后~([3,4])。本文就尼莫地平在a SAH治疗中研究进展进行综述。     

丹奥与尼莫地平防治蛛网膜下腔出血后脑血管痉挛的疗效对比

目的　观察丹奥防治蛛网膜下腔出血 (SAH)后脑血管痉挛 (CVS)的疗效并与尼莫地平进行比较。方法　将 64例SAH病人随机分成丹奥组和尼莫地平对照组各 3 2例 ,两组均在发病 48h内接受脱水、止血、控制血压等基础治疗 ,丹奥组应用注射用奥扎格雷钠 80mg加入生理盐水 2 5 0ml中静滴 1次 /d ,连用 14d ;尼莫地平组应用尼莫地平注射液每日 2 0mg加入生量盐水 5 0 0ml中持续2 4h静滴 ,连用 14d。结果　丹奥组CVS发生率和SAH死亡率与尼莫地平组经Ridit分析无显著差异。结论　丹奥防治SAH后CVS与尼莫地平具有相同疗效 ,使用方便、安全 ,且无增加再出血的危险。     

脑池内灌注与静脉滴注尼莫地平预防蛛网膜下腔出血后脑血管痉挛的效果对比

目的探讨脑池内灌注与静脉滴注尼莫地平预防蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的效果。方法将80例SAH患者随机分为两组,两组患者均行开颅动脉瘤夹闭术,A组(n=40)在术中及术后予以脑池内灌注尼莫地平,B组(n=40)术后静脉滴注尼莫地平,对比两组患者术后的CVS发生率及预后效果。结果 A组术后的症状性CVS发生率为40.0%,明显低于B组(65.0%)(P0.05)。A组术后3d、5d、7d、14d的CVS发生率均显著低于B组;A组术后第2天的脑脊液(CSF)引流量以及引流液中的红细胞含量均明显少于B组(P0.05)。A组患者的预后良好率为75.0%,显著高于B组的50.0%(P0.05)。结论比较静脉滴注尼莫地平,脑池内灌注尼莫地平预防动脉瘤性SAH后CVS的效果更为显著,并发症更少。     

6-氨基己酸与尼莫地平联合治疗蛛网膜下腔出血的临床研究

目的　探讨 6 氨基己酸 (EACA)与尼莫地平联合治疗对蛛网膜下腔出血 (SAH)患者预后的影响。方法　SAH患者 10 9例 ,随机分为治疗组 (6 0例 ,EACA合并尼莫地平治疗 )及对照组 (4 9例 ,单用尼莫地平治疗 ) ,两组均于发病 3天内接受治疗。 1月后根据GOS评定疗效 ,并观察并发症的发生情况。结果　两组的治愈率、致残致死率及Barthelindexes(BI)并无明显差别。EACA治疗组再出血的发生率 (15 % )较对照组(33% )明显减少 (P <0 .0 5 ) ,而两组中脑缺血和其他并发症的发生率基本相同。结论　EACA与尼莫地平合用并不能改善SAH患者的预后 ,但可降低再出血的发生率     

丹奥与尼莫地平防治蛛网膜下腔出血后脑血管痉挛的疗效对比

目的 观察丹奥防治蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的疗效并与尼莫地平进行比较。方法将64例SAH病人随机分成丹奥组和尼莫地平对照组各32例，两组均在发病48h内接受脱水、止血、控制血压等基础治疗，丹奥组应用注射用奥扎格雷钠80mg加入生理盐水250ml中静滴1次／d，连用14d；尼莫地平组应用尼莫地平注射液每日20mg加入生量盐水500ml中持续24h静滴，连用14d。结果 丹奥组CVS发生率和SAH死亡率与尼莫地平组经Ridit分析无显著差异。结论丹奥防治SAH出CVS与尼莫地平具有相同疗效，使用方便、安全，且无增加再出血的危险。     

鼠脑血管痉挛时尼莫地平对体感诱发电位的影响

目的 探讨蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）对体感诱发电位（SEP）的影响,及尼莫地平（ND）的保护作用。方法 对单纯SAH组和ND处理组大鼠观察手术前后基底动脉管径,并检测24h内局部脑血流量（rCBF)、SEP潜伏期及脑组织内皮素-1（ET-1）含量的动态变化。结果 SAH组大鼠在诱导SAH后rCBF立即降低,并持续24h,同时有基底动脉痉挛;SAH后1h开始至24hSEP潜伏期逐渐延长,脑组织ET-1含量显著增加,ND处理组大鼠上述变化均较轻。结论 SAH后CVS可通过脑血流的降低,脑组织ET-1增加而导致SEP潜伏期延长,ND通过拮抗脑组织ET-1变化而对之具有保护作用。     

辛伐他汀治疗蛛网膜下腔出血的疗效观察

目的探讨辛伐他汀对蛛网膜下腔出血治疗作用。方法将连平县人民医院2003年3月～2005年3月128例蛛网膜下腔出血的住院患者随机分为2组（所有病例均给以常规治疗并静脉注射尼膜地平）：治疗组（口服辛伐他汀组）64例，给予口服或者鼻饲辛伐他汀20mg，每日2次；对照组（常规治疗组）64例，给予安慰剂口服，每日2次。14d后对患者进行神经功能缺损评分并行头颅CT等检查。结果14d的治疗后治疗组较对照组神经功能缺损评分明显降低，二者比较差异有显著性意义（P〈0.05）。脑血管痉挛的发生率：治疗组为4例，对照组11例，二者比较有显著性意义（P〈0，01）。结论口服辛伐他汀能明显改善蛛网膜下腔出血后神经功能缺损评分。     

The effect of ecdysterone on cerebral vasospasm following experimental subarachnoid hemorrhage in vitro and in vivo

OBJECTIVES: Cerebral vasospasm has been the dreaded complication of ruptured intracranial aneurysms. Worldwide effort has led to many promising experimental treatments but none was confirmed to be effective in clinical trials. Ecdysterone is an insect steroid hormone. Our previous study showed that ecdysterone might prevent cerebral vasospasm in vitro. Even after all these works, rare attempts have been made to test the effect of ecdysterone on vascular adventitial fibroblast (VAF) proliferation, a process known to play an important role in various pathogenic vascular conditions. Thus, we tested the hypothesis that ecdysterone could affect VAF characteristics and have an effect on SAH induced cerebral vasospasm. METHODS: OxyHb of 100 microM was used in the in vitro study to mimic the clinical situation. The effect of OxyHb on the cell proliferation and migration of cultured aortic smooth muscle cells was investigated. In the in vivo study, 20 rabbits were equally divided into four groups: control group, SAH group, SAH/nimodipine group and SAH/ecdysterone group. Changes in neurological function and cerebral angiograms were observed after SAH. RESULTS: OxyHb increased the proliferation of vascular adventitial fibroblasts at 24 hours. Ecdysterone co-treatment was apparently similar to the suppression of proliferation. Cell cycle analysis indicated that ecdysterone inhibited the progression of vascular adventitial fibroblasts from G1 to S. The results of the migration assay showed that 100 microM OxyHb obviously prompted vascular adventitial fibroblast migration and that ecdysterone would attenuate this effect. In the SAH/nimodipine and SAH/ecdysterone groups, neurological deficit, cerebral vasospasm and structural changes in basilar artery were alleviated with nimodipine or ecdysterone treatment. CONCLUSION: Ecdysterone could affect vascular adventitial fibroblast characteristics and attenuate vasospasm after SAH.     

细胞凋亡对蛛网膜下腔出血后脑血管痉挛发病机制的研究

脑血管痉挛是蛛网膜下腔出血的重要并发症,也是造成患者死亡和致残最重要的原因.脑血管痉挛已经成为临床研究的热点,尤其是近几年在发病机制、诊断和治疗方面取得了很大进展.凋亡不同于坏死,是细胞的程序性死亡.最近的研究表明蛛网膜下腔出血以后脑血管内皮细胞存在有凋亡的发生,而且此现象在血管痉挛形成机制中起着重要的作用.对脑血管痉挛凋亡机制的深入研究,必将有助于临床上防治脑血管痉挛.     

川芎嗪对实验性SAH后CVS防治作用的研究

目的研究兔症状性蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)与内皮素(ET)和一氧化氮(NO)的关系及川芎嗪的保护作用.方法采用双侧颈动脉结扎和枕大池二次注血制成兔SAH模型,观察SAH前后动物进食量和神经功能改变,用放射免疫方法和硝酸还原酶法分别测定血液和脑脊液中ET和NOx-含量,以氢清除法测定局部脑血流量(rCBF).结果SAH后大部分动物进食量有不同程度的下降,所有动物均有不同程度的神经功能障碍和rCBF下降.SAH后血液和脑脊液中ET含量增加,NOx-含量下降(P＜0.01).上述变化随出血时间延长和出血量的增大而增加.川芎嗪治疗组上述变化均有不同程度的改善.结论双侧颈动脉结扎后枕大池二次注血可制成可靠的兔症状性SAH后CVS的动物模型.兔SAH后ET和NO含量的改变与CVS的发生密切相关,并进而导致临床症状的恶化.川芎嗪可通过抑制SAH后ET和NO的变化而对CVS的发生和发展起到防治作用.     

Feasibility and safety of intrathecal nimodipine on posthaemorrhagic cerebral vasospasm refractory to medical and endovascular therapy

OBJECTIVE: The effectiveness of balloon angioplasty and intra-arterial infusion of vasodilating agents for patients suffering from severe vasospasm following aneurysmal subarachnoid haemorrhage (SAH) is often unsatisfying and there is still demand for further last resort treatment strategies. In the current prospective study, we attempted the intrathecal lavage administration of nimodipine in cases of severe cerebral vasospasm that were refractory to medical and endovascular therapy. METHODS: Eight of 146 patients with aneurysmal SAH were included in the prospective study, which had been approved by the local ethics committee. Treatment was instituted by intraventricular nimodipine bolus (0.4mg), followed by a continuous lumbar intrathecal infusion (0.4mg/h). Effectiveness was monitored angiographically, with transcranial Doppler (TCD), perfusion CT (pCT), and by neurological examination during treatment course and follow-up. RESULTS: The neurological condition improved directly in three patients and remained unchanged in four patients. Seventeen (70.8%) CT perfusion analyses revealed improved perfusion. A reduction of vasospasm was seen angiographically by digital subtraction angiography (DSA) in seven (66.6%) investigations. Additional ischaemic infarction after onset of the intrathecal therapy was documented in two (25%) patients. There were no serious adverse effects observed. CONCLUSION: The present study has for the first time demonstrated the feasibility and safety of intrathecal nimodipine lavage in patients with severe vasospasm resistant to the established medical and endovascular treatment strategies. The results of the study are therefore encouraging, and further experimental and clinical trials should be carried out so as to investigate the efficacy of intrathecal nimodipine lavage in vasospasm therapy.     

自由基清除剂对减少大鼠SAH后CVS的研究

目的 通过建立大鼠蛛网膜下腔出血模型并应用自由基清除剂对其进行治疗,观察大鼠脑基底动脉的病理变化及其管壁上细胞间粘附因子1（ICAM-1）、白介素6（IL-6）在治疗前、后的动态变化,为进一步明确脑血管痉挛（cerebral vasospasm,CVS）的发病机制及治疗脑血管痉挛提供理论依据.方法 取Sprague Dawley （SD）大鼠98只,观察正常大鼠及治疗大鼠SAH前后基底动脉管径的变化;行免疫组化染色对大鼠脑基底动脉进行免疫学检测,观察ICAM-1、IL-6在血管壁上表达的动态变化;行原位杂交检测观察大鼠脑基底动脉管壁上ICAM-1、IL-6在分子水平表达的动态变化.结论 ①自由基清除剂能够抑制SAH后CVS的免疫炎症反应;②应用自由基清除剂对防治CVS有一定效果,能够有效缓解CVS.     

Nimodipine Attenuation of Early Brain Dysfunctions Is Partially Related to its Inverting Acute Vasospasm in a Cisterna Magna Subarachnoid Hemorrhage (SAH) Model in Rats

ABSTRACT Subarachnoid hemorrhage (SAH)-induced brain injury is highly related to neurological deficits and mortality. Regional cerebral blood flow (rCBF) changes and vasoconstriction are two complications that occur soon after SAH experimentally. In this study we investigated the changes in rCBF and vertebro-basilar arterial diameter in a cisterna megna SAH model in Sprague-Dawley rats and intended to explore whether improving early rCBF reduction and cerebral vasospasm could contribute to alleviating blood-brain barrier (BBB) dysfunction. In rats for rCBF, vasospasm and BBB permeability assessments, nimodipine (NDP) or saline was administered intravenously 5 minutes after SAH. rCBF within the first 60 minutes after SAH was measured by laser Doppler flowmetry. BBB permeability indexed by Evans Blue extravasation was assessed 4?hours after SAH. Angiography for the caliber changes of the vertebro-basilar artery were conducted 30 minutes post SAH. Pronounced rCBF reduction and vasospasm were observed soon after SAH, followed by BBB permeability increment. NDP administration could improve rCBF and attenuate vasospasm, followed by the alleviation of BBB permeability. Our results demonstrate that early improvement of cerebral circulation by NDP may contribute to the reduction in brain injury indexed by BBB disruption.     

上胸段硬膜外阻滞与尼莫地平减轻兔脑血管痉挛作用的比较

目的比较上胸段硬膜外阻滞（HTEB）减轻兔蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）的作用是否优于尼莫地平。方法切开置管法制备HTEB模型的新西兰兔60只,按随机数字表法随机分成4组（n=15）：假手术组、对照组）、HTEB治疗组和尼莫地平治疗组。＂枕大池二次注血法＂（0.5ml/kg）制成兔SAH模型,1、7和14d后用经颅多普勒检测基底动脉平均血流速度（Vm）。处死后取基底动脉,光镜下观察其形态学变化。结果与假手术组相比,对照组、HTEB治疗组和尼莫地平组的基底动脉Vm均明显升高（P〈0.01）;但HTEB治疗组和尼莫地平组的基底动脉Vm明显低于对照组（P〈0.05）,而两治疗组差异无统计学意义（P〉0.05）。光镜下,对照组基底动脉管壁增厚、管腔变窄;两治疗组管壁增厚不明显,管腔仍有狭小,较对照组明显改善;两治疗组之间血管壁变化无明显差异。结论 HTEB减轻兔SAH后CVS的程度与尼莫地平相当。     

刺五加防治蛛网膜下腔出血后脑血管痉挛的作用机制

目的 探讨刺五加注射液预防和治疗蛛网膜下腔出血后脑血管痉挛(cerebral vasospasm,CVS)的疗效及其机制。方法 根据1994年中华医学会第4届全国脑血管病学术会议修订的诊断标准,44例蛛网膜下腔出血患者,随机分为刺五加组(20例)和对照组(24例),两组均于发病48h内接受治疗。对照组采用常规药物治疗,刺五加组在常规疗法基础上加用刺五加注射液100ml,每日1次静脉滴注,共治疗7d。采用放射免疫分析法测定血浆内皮素水平。结果 应用刺五加注射液治疗1个月后,刺五加组CVS的发生率与病死率(均为10.0％)明显低于对照组(37.5％),差异有显著性意义(均P<0.05)。再出血发生率分别为15.0％和16.7％,两组比较差异无显著性意义(P>0.05)。刺五加组血浆内皮素水平明显低于对照组(P<0.05或P<0.01)。结论 刺五加注射液防治蛛网膜下腔出血后CVS疗效确实,既可促进神经功能尽快恢复,又不增加再出血的危险性。其机制之一可能系与降低血浆内皮素水平有关。