亚低温对前脑缺血再灌注损伤沙土鼠海马p-ERK、p-JNK水平的影响

目的 研究亚低温对前脑缺血再灌注损伤沙土鼠海马磷酸化胞外信号调节激酶（p-ERK）及磷酸化c-Jun氨基末端蛋白激酶（p-JNK）水平的影响。方法 蒙古沙土鼠120只，随机分为4组（n=30）：常温假手术组（SH组）、常温缺血再灌注组（IR组）、低温假手术组（HSH组）、常温缺血低温再灌注组（HIR组）。腹腔注射1％戊巴比妥钠40mg／kg麻醉后，分离出双侧颈总动脉，IR组、HIR组分别夹闭双侧颈总动脉，5min后恢复脑血流灌注，IR组再灌注时维持正常体温（36．5—37．5℃），HIR组再灌注即刻开始降温，10min内降至32．5—33．5℃，并维持4h；SH组、HSH组只分离双侧颈总动脉不夹闭，SH组维持正常体温，HSH组分离双侧颈总动脉后5min开始降温，10min内降至32．5—33．5℃，并维持4h。每组于再灌注2h,4h、1d、3d、5d分别随机取6只动物，采用开阔法观察沙土鼠的行为学，行为学观察完毕立即处死大鼠，取脑组织，采用TUNEL法检测海马CA1区、CA3区细胞凋亡情况，免疫组化法测定海马CA1区、CA3区、DG区p-ERK、p-JNK的水平。结果HIR组再灌注1—5d沙土鼠行为学异常及海马凋亡细胞计数较IR组降低（P〈0．01）；与SH组或HSH组比较，IR组及HIR组再灌注期间海马CA3区及DG区p-ERK水平增加（P〈0．05），但IR组与HIR组比较差异无统计学意义；4组海马CA1区均无p-ERK表达。与sH组比较，IR组再灌注2h-5d海马CA1区、CA3区p-JNK水平增加，且HIR组再灌注2h-1d海马CA1区、CA3区p-JNK水平低于IR组（P〈0．05）。结论 亚低温（32．5-33．5℃）4h可减轻沙土鼠脑缺血再灌注损伤，其机制与抑制再灌注早期p-JNK的激活有关，而与p-ERK水平无关。     

多形核粒细胞渗透和早期NF-kB活性与深低温停循环肺损伤的评估

目的研究深低温停循环（deep hypothermia and circulatory arrest，DHCA）不同时段肺组织内核转录因子kappaB（nuclearfactor—kappaB，NF-kB）、炎症因子和多形核粒细胞（polymorphonuclear cells，PMNs）的变化，推测PMNs渗透和早期NF-kB活性在DHCA肺损伤早期的作用，探讨其可能的机制，为肺保护策略提供实验依据。方法将12只幼猪随机分为两组，每组6只，常温平行循环组（对照组）和DHCA缺血-再灌注组（实验组），分别在不同时间点检测NF-kB和炎症因子的变化。结果两组在平行循环前肺组织标本中NF-kB均为阴性，胞核未见棕染，组间比较差异无统计学意义（P〉O．05）。实验组在缺血-再灌注0．5h时肺组织细胞核内NF-kB的表达达到高峰，且棕染的细胞核以PMNs为主；而对照组平行循环后各时间点比较差异无统计学意义，肺组织标本仍为弱阳性。实验组肿瘤坏死因子-α（TNF-α）在缺血-再灌注1h时较再灌注前含量有显著性变化（P〈0．05），白细胞介素-8（IL-8）、白细胞介素-6（IL-6）含量则在缺血-再灌注1．5h时较再灌注前有显著的变化（P〈0．05）；对照组平行循环后各时点与平行循环前比较差异有统计学意义（P〈0．05），但平行循环后各时间点比较差异无统计学意义（P〉0．05）。结论DHCA的早期激活NF-KB可能在DHCA肺损伤中起着重要的作用。     

亚低温对兔肝缺血再灌注损伤的保护作用

目的：研究应用冰毯导致亚低温对肝缺血再灌注损伤的保护作用。方法：30只兔随机均分为3组：常温组、亚低温组和对照组。组织气体分析仪持续测定兔肝组织氧压（PtiO2）；光镜及电镜观察肝脏病理改变；全自动生化仪测定血清丙氨酸氨基转氨酶（ALT）。结果：亚低温组与常温组兔在肝缺血30min、再灌注30min和60min期间的PtiO2值、血清ALT值差异均有显著性（P＜0．05）。亚低温组较常温组肝缺血再灌注的理性损伤明显改善。结果：常温下入肝血流阻断可以导致肝缺血再灌注损伤。亚低温能显著减轻肝缺血再灌注后肝细胞功能障碍和病理损害程度，其作用机制与亚低湿能降低缺血期肝细胞的耗氧量、减轻再灌注后的微循环障碍和防治肝细胞线粒体的损伤有关。     

深低温停循环中不同脑灌注方式皮层超氧化物歧化酶、丙二醛及超微结构的变化

目的观察不同脑灌注方法对深低温停循环（DHCA）中脑皮质超氧化物歧化酶（SOD）、丙二醛（MDA）及超微结构的影响，比较不同灌注方式的脑保护效果。方法健康成年杂种犬15条，随机分为3组。Ⅰ组单纯行DHCA为对照，Ⅱ组DHCA＋逆行脑灌注（RCP），Ⅲ组DHCA＋选择性顺行脑灌注脑保护（SACP）。转流降温至鼻咽部温18℃时停循环90min，然后复温再灌注90min。结果停循环期皮层SOD活性下降而MDA含量上升，复温再灌注时变化更明显，各时间点差异有统计学意义（P〈0．05）。增加或下降程度以Ⅰ组最为明显，Ⅱ组次之，Ⅲ组最小。Ⅱ、Ⅲ组与Ⅰ组比较SOD、MDA变化明显减轻（P〈0．01），Ⅱ、Ⅲ组间亦差异有统计学意义（P〈0．05），与电镜观察结果一致。结论深低温停循环期间SACP有明显脑保护作用，RCP亦可减轻DHCA中脑损害。     

卵巢浆液性囊腺癌术后双途径化疗的临床观察

目的 探讨Ⅱ期以上卵巢浆液性囊腺癌患者术后行腹腔持续灌注联合双途径化疗的临床疗效。方法 76例Ⅱ-Ⅳ期卵巢浆液性囊腺癌术后随机分为两组：联合组40例,腹腔持续灌注联合静脉双途径化疗6次;对照组36例,常规静脉化疗6次。两组化疗均采用PCH方案（顺铂＋环磷酰胺＋羟基喜树碱）,并均于术后21-28 d开始化疗。结果 联合组1,3年生存率分别为97.5%（39/40）和85.0%（34/40）,对照组分别为94.4%（34/36）和50.0%（18/36）。两组1年生存率无显著性差异（P〉0.05）,3年生存率有显著性差异（P〈0.05）。联合组和对照组Ⅱ度以上胃肠道反应发生率分别为27.5%（11/40）和77.8%（28/36）,有显著性差异（P〈0.01）。两组骨髓抑制差异无显著性（P〉0.05）。结论 双途径化疗可延长Ⅱ-Ⅳ期卵巢浆液性囊腺癌患者术后生存期,降低Ⅱ度以上胃肠道反应发生率。     

不同深低温停循环方法对脑组织S-100蛋白表达的影响

目的观察不同深低温停循环方法对脑组织S—100蛋白表达及组织结构的影响。方法将18只实验犬随机分为3组，深低温停循环（deep hypothermic circulatory arrest，DHCA组）组，深低温停循环结合逆行脑灌注（retrograde cerebral perfusion，RCP，DHCA＋RCP组）组，深低温停循环结合顺行性间断脑灌注（intermittent antegrade cerebral perfusion，IACP，DHCA＋IACP组）组。3组犬体外循环开始后将鼻咽温降至18℃，随后停循环90min，开放循环后复温至36℃，随后停机。在停循环前、停循环后45min、90min及开放循环后15min和30min由颈静脉插管留取血液标本进行S-100蛋白含量测定。手术结束时取脑海马组织作透射电子显微镜检查，观察脑组织及神经细胞超微结构的变化。结果3组犬在停循环前颈静脉血S-100蛋白含量差异无统计学意义（P〉0．05），停循环后DHCA组和DHCA＋RCP组S-100蛋白含量较停循环前显著升高（P〈0．01），DHCA＋IACP组S-100蛋白含量停循环前后无显著变化。结论DHCA时间较长时，脑组织会发生缺血缺氧性损伤；RCP对脑组织有一定的保护作用，但易发生脑组织及神经细胞水肿；IACP的脑保护效果较为理想。     

动脉瘤性蛛网膜下腔出血后脑血管痉挛和围术期容量治疗

背景 动脉瘤破裂蛛网膜下腔出血后脑血管痉挛(cerebral vasospasm,CVS)是一个常见而严重的并发症.CVS造成的继发性脑组织缺血或迟发性脑损伤严重影响患者的预后,是动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者伤残和死亡的主要因素. 目的 探究围术期液体治疗和循环容量管理在aSAH后CVS预防和治疗中的有效性,为减少脑动脉瘤手术后CVS发生、改善预后提供参考. 内容 探究动脉瘤破裂蛛网膜下腔出血后CVS病因、病理生理以及如何选择合适的液体进行容量治疗和三高疗法来防治CVS的发生. 趋向 深入研究脑动脉瘤破裂出血后CVS的发病机制和探讨围术期液体治疗以及循环容量管理,为临床防治CVS提供新的思路和方法.     

米非司酮对围绝经期功血的治疗作用

目的探讨米非司酮对围绝经期功血的治疗作用。方法对178例围绝经期功血患者分组治疗,治疗组每日口服米非司酮12.5mg,连服3个月。对照组每日口服醋酸甲羟孕酮片4mg＋己烯雌酚0.5mg,以20d为1个周期,3个周期为1个疗程,治疗前后对比各指标,评估用药疗效。结果治疗组与对照组近期疗效比较,差异无统计学意义（P〉0.05）;远期疗效比较,治疗组优于对照组,差异有统计学意义（P〈0.05）;治疗组副反应发生率明显低于对照组,激素水平比较,差异有统计学意义（P〈0.05）;改善贫血方面两者均有疗效,差异无统计学意义（P〉0.05）。结论米非司酮方案治疗围绝经期功血优于雌孕激素联合方案。     

亚低温治疗重型颅脑损伤临床分析

目的研究亚低温对重型颅脑损伤患者颅内压（ICP）及并发症的影响。方法重型颅脑损伤患者68例,随机分为亚低温组（n=38）及常温常规治疗组（n=30）。亚低温组接受32℃～35℃低温治疗,常温常规治疗组除亚低温治疗外,其余治疗同亚低温组。比较两组的ICP、预后和并发症的差异。结果亚低温治疗组伤后ICP显著低于常温常规治疗组（P（0.01）。预后显著好于常温常规治疗组（P〈0.05）。应激性溃疡、肝肾功能异常和外伤性癫痫的发生率显著低于常温常规治疗组（P〈0.01）。结论亚低温对重型颅脑损伤患者ICP升高有明显的治疗作用,可以改善重型颅脑损伤患者的预后,减少全身并发症。     

醒脑静注射液对自发性蛛网膜下腔出血后脑血管痉挛及炎症因子的影响

目的 观察醒脑静注射液对自发性蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）血管内皮生长因子（VEGF）、可溶性血管内皮细胞黏附因子-1（sVCAM-1）、核因子（NF-κB）及脑血流速度的影响。 方法 选择SAH 患者66例,随机数字表法分为治疗组34例和对照组32例,两组均进行保持患者生命体征稳定、降低颅内压、纠正水和电解质平衡紊乱、调控血压和抗纤溶药物防治再出血等常规治疗。对照组在常规治疗基础上采用尼莫地平40 mg,po,tid,连用21 d。治疗组在对照组治疗基础上加用醒脑静注射液30 mL加入0.9%氯化钠注射液250 mL静脉滴注,qd,连用21 d为1个疗程。比较两组治疗前后外周血超敏C反应蛋白（hs-CRP）、VEGF、sVCAM-1和NF-κB水平,观察经颅多普勒彩超（TCD）,比较两组出院时格拉斯哥预后评分（GOS）。结果 与对照组比较,治疗组第1天VEGF、sVCAM-1、NF-κB和hs-CRP差异无统计学意义（均P>0.05）,第3天sVCAM-1和NF-κB显著性下降（P<0.05）;第7,21天VEGF、sVCAM-1、NF-κB和hs-CRP含量明显降低（P<0.05）。与对照组比较,治疗组第1天大脑中动脉（MCA）、大脑前动脉（ACA）和大脑后动脉（PCA）血流速度差异无统计学意义（P>0.05）,第3天ACA显著降低（P<0.05）,第7,21天MCA、ACA和PCA显著下降（P<0.05）。治疗组出院时GOS 为（4.78±0.39）分,对照组（4.06±0.56）分,差异有统计学意义（P<0.05）。治疗组不良反应发生率8.82%。结论 醒脑静干预治疗可以下调SAH 后CVS 的VEGF、sVCAM-1和NF-κB过度表达,同时降低脑血流速度,缓解脑血管痉挛,对SAH 后CVS患者有一定脑保护作用。     

标准大骨瓣减压术联合选择性脑局部亚低温对重型颅脑损伤的疗效分析

目的探讨标准大骨瓣减压术联合选择性脑局部亚低温对重型颅脑损伤的治疗效果。方法回顾性分析2000年1月至2007年12月91例在本院神经外科住院的重型颅脑损伤的患者,均行标准大骨瓣减压术,根据术后有无行选择性脑局部亚低温治疗分为A、B两组,比较术后颅内压的变化及治疗预后。结果两组术后颅内压均在同一水平,在行亚低温治疗后,A组在术后24小时、48小时、72小时颅内压明显较治疗前降低,B组在术后48小时、72小时颅内压明显较治疗前降低,差异有统计学意义（P〈0．05）;A组在术后24小时、72小时的颅内压明显低于B组,差异有统计学意义（P〈O．05）。A组治疗有效率为42．9％,明显高于对照组21．4％,差异有统计学意义（P〈O．05）。结论标准大骨瓣减压术是救治重型颅脑损伤的患者有效的方式,术后给予脑局部亚低温能显著降低颅内压,改善患者预后。     

高压氧对脑肿瘤、脑动脉瘤术后康复疗效的观察

目的：探讨高压氧（HBO）治疗脑肿瘤、脑动脉瘤术后康复的临床疗效。方法选取我院2009年12月~2013年12月收治的脑肿瘤、脑动脉瘤术后患者200例,根据治疗方法不同分为两组,将100例HBO治疗的脑肿瘤、脑动脉瘤术后患者设为观察组,将病情相似未作HBO治疗的100例患者设为对照组,两组均常规药物治疗。采用头颅彩色多普勒超声检查患者脑血管痉挛（CVS）情况,并采用神经功能缺损评分和日常生活活动能力评定评判患者临床恢复情况,并对临床疗效进行对比分析。结果两组患者治疗前NF评分和Barthel评分比较差异无统计学意义（P＞0.05）;观察组患者治疗后NFD评分和Barthel评分与对照组治疗后比较差异均有统计学意义（P＜0.05）;两组患者治疗前大脑中动脉流速及CVS比较差异无统计学意义（P＞0.05）;观察组患者治疗后大脑中动脉流速及CVS与对照组治疗后比较差异均有统计学意义（P＜0.05）。结论HBO综合治疗效果显著,能够减少神经功能缺损评分,提高患者生活质量,值得推广使用。     

去骨瓣减压对外伤性脑血管痉挛状态影响的研究

目的 通过对去骨瓣减压术后患者情况综合研究外伤性脑血管痉挛（CVS）的危险因素. 方法 对本院2010年3月至2011年3月收治的30例幕上急性硬膜外血肿合并外伤性蛛网膜下腔出血的脑疝患者,首先予经颅多普勒超声（TCD）检测,并予脑室穿刺行颅内压动态监测,再行去骨瓣减压术,术后连续7天行TCD及颅内压监测并作相关数据分析. 结果 18例发生CVS（占60％）,脑中线结构钟摆程度≥2cm的CVS发生率显著高于脑中线结构钟摆程度＜2cm;t-SAH积血Hijdra法计算6分以下20例中有9例（45％）、6以上10例中有9例（90％）发生CVS;脑疝至手术处理时间2小时以上3例中有3例（100％）、2小时以下27例中有15例（55.6％）发生CVS;手术进行硬膜下探查19例中有8例（50％）、未探查11例中有10例（90.9％）发生CVS;年龄＞50岁18例中有6例（33.3％）、＜50岁12例（40％）中有12例（100％）发生CVS. 结论 经血肿清除及去骨瓣减压术后的患者所发生的脑血管痉挛情况与患者术前术后脑中线结构钟摆程度、蛛网膜下腔出血量、脑疝至手术处理时间的长短、是否进行硬膜下探查、年龄等情况有关.     

体温控制对重型颅脑损伤患者脑脊液中caspase-3、caspase-9及预后的影响

目的 探讨体温控制对重型颅脑损伤患者神经细胞凋亡及预后的影响. 方法 将42例重型颅脑损伤患者随机分为两组:实验组(n=22)患者采用亚低温治疗仪将患者急性期7d内的肛温持续控制在36℃ ～37℃;对照组(n=20)未控制体温,当体温超38℃时予常规方法降低体温.收集患者入院后第1、3、5、7d的脑脊液标本,比较两组患者脑脊液中caspase-3、caspase-9的浓度及预后的差异. 结果 ①组间比较,caspase-3及caspase-9的浓度值均在第1d无统计学差异(P＞0.05);实验组第3、5及7d浓度均低于对照组(P＜0.05).②根据伤后3～6个月GOS评分,实验组患者预后良好率高于对照组(P＜0.05). 结论 体温控制在36℃～37℃可降低重型颅脑损伤患者脑脊液中caspase-3及caspase-9的浓度,降低预后不良的发生率,改善患者的预后.     

Posttreatment with adenovirus-mediated gene transfer of calcitonin gene-related peptide to reverse cerebral vasospasm in dogs

OBJECT: Gene transfer to cerebral vessels is a promising new therapeutic approach for cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was undertaken to explore whether a delayed treatment with adenovirus encoding the prepro-calcitonin gene-related peptide (CGRP), 2 days after initial blood injection, reduces cerebral vasospasm in a double-hemorrhage model of severe vasospasm in dogs. METHODS: In 20 dogs, arterial blood was injected into the cisterna magna on Days 0 and 2. Thirty minutes after the second blood injection, the animals received either adenovirus encoding the prepro-CGRP gene (AdCMVCGRP-treated group, eight dogs) or adenovirus encoding the beta-galactosidase gene (AdCMVbeta gal-treated group, six dogs) under the cytomegalovirus (CMV) promoter. One group of dogs did not receive treatment and served as controls (control SAH group, six dogs). Angiography was performed on Days 0 and 7 to assess cerebral vasospasm. On Day 7 following angiography, the animals were killed and their brains were stained with X-gal to detect the distribution of gene expression. Cerebrospinal fluid (CSF) was also tested for CGRP immunoreactivity. Severe vasospasm was observed in control SAH dogs on Day 7, and the mean basilar artery (BA) diameter was 53.4 +/- 5.5% of the value measured on Day 0. Treatment with AdCMVbeta gal did not alter vasospasm (the BA diameter was 55 +/- 3.9% of that measured on Day 0). The leptomeninges and adventitia of the BAs of dogs treated using AdCMVbeta gal demonstrated positive staining with X-gal. High levels of CGRP were measured in CSF from dogs that received AdCMVCGRP. In the group treated with AdCMVCGRP, vasospasm was significantly reduced (the BA diameter was 78.2 +/- 5.3% of that measured on Day 0, p < 0.05 compared with the control SAH group and the AdCMVbeta gal group). CONCLUSIONS: In a model of severe vasospasm in dogs, gene transfer of CGRP after injection of blood attenuated cerebral vasospasm after SAH.     

亚低温对重症脑外伤免疫功能与获得性肺炎的影响及与预后关系的研究

目的研究亚低温对重型颅脑损伤患者免疫功能的影响，及院内获得性肺炎的发生与细菌分布，与预后的关系。方法将85例重型颅脑损伤患者（GCS评分≤8分）随机分为亚低温治疗组和常温治疗组。亚低温组45例．伤后24小时内采用亚低温治疗，使直肠温度控制在33℃～35℃，维持5～7天；常温治疗组40例，其它治疗两组基本相同。分别在入院后第1、3、5、7及14天检测两组患者血清免疫球蛋白与补体水平和外周血T-淋巴细胞转化率的动态变化，并分析两组患者院内获得性肺炎的发生情况。感染细菌的分布，两组患者之间预后的比较。结果亚低温治疗组与常温治疗组两组患者的免疫球蛋白水平和T-淋巴细胞转化率在第1、3、14天均无显著差异（P〉0．05），而在第5、7天有统计学上意义（P〈0．05）。而在院内获得性肺炎的发生上与细菌类型上无显著差异。两者之间的预后亚低温治疗组明显好于非亚低温治疗组。结论亚低温治疗能明显改善重型颅脑损伤患者的预后，但在长时程的治疗过程中。会明显抑制重型颅脑损伤患者的免疫功能，而在亚低温治疗期间患者院内获得性肺炎的发生率并没有明显增加。     

全脑CT灌注同步CT血管成像评价蛛网膜下腔出血后表现及预后

目的探讨全脑CT灌注同步CT血管成像评价蛛网膜下腔出血(SAH)后表现及预后的价值。方法 SAH患者71例,按发病时间分为急性期(3天内)与延迟期(4～15天)。所有患者接受CT平扫、CTA及CT灌注成像(CTP),以动脉期数据重建VR脑动脉图像,生成全脑灌注脑血容量(CBV)、脑血流量(CBF)、平均通过时间(MTT)、达峰时间(TTP)图像,判断有无脑血管痉挛,分析不同预后患者CTP各参数的变化。结果 71例SAH患者中,急性期SAH患者44例,预后差者占31.82%(14/44),延迟期SAH患者27例,其中预后差者占40.74%(11/27,χ2=0.584,P=0.445)。急性期和延迟期预后好与预后差患者的CTP各参数差异均有统计学意义(P均<0.05)。结论CTP结合CTA同步检查有助于判断不同时期SAH继发脑血管痉挛患者的预后,指导临床及时进行合理治疗。     

The correlation between immunological reaction in the arterial wall and the time course of the development of cerebral vasospasm in a primate model

To investigate the role of immunological reactions in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH), the authors studied the correlation between immune/inflammatory reactions in the arterial wall and the time course of vasospasm in primates. Twenty monkeys were divided into four groups of 5 animals each: 1) a control group of sham-operated animals, 2) animals subjected to angiography 3 days after the induction of SAH (3-day SAH), 3) animals subjected to angiography 7 days after SAH (1-week SAH), and 4) animals subjected to angiography 7 and 14 days after SAH (2-week SAH). To induce SAH, the main cerebral arteries on the right were dissected free of the arachnoid, and an autologous blood clot was placed around the arteries. To evaluate vasospasm, all animals underwent a baseline angiogram before SAH; angiography was repeated at different intervals in each group, as outlined above. Histopathological changes and the deposition of the immunoglobulin IgG in the arterial wall were evaluated immunohistochemically in each group. The cerebral arteries on the side of the clot showed evidence of mild vasospasm (-24.6% reduction) on the angiogram performed on Day 3, severe vasospasm (-51.7%) on Day 7, and mild vasospasm (-12.8%) on Day 14. The infiltration of inflammatory cells was most marked in the spastic arterial wall in the 1-week SAH group. In the 2-week SAH group, severe myonecrosis and intimal disruption were observed, even in the vessels that showed only mild vasospasm, and the inflammatory reactions had almost abated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of cerebral vasospasm in patients with subarachnoid hemorrhage using single photon emission computed tomography

Cerebral vasospasm (CVS) occurs as a result of the breakdown in cerebral autoregulation mechanisms. Because cerebral vasospasm can occur after subrachnoid hemorrhage (SAH), it is important to evaluate borderline perfusion. Evaluation of borderline vascular insufficiency is important to reduce ischemic complications. In this study 25 patients with SAH were investigated by somatosensory evoked potentials (SEP), computed tomography (CT), digital subtraction angiography (DSA) and single photon emission computed tomography (SPECT) in order to predict borderline ischemic areas. Clinical grades were also correlated with these investigations. Thirteen patients had symptomatic vasospasm and 15 patients had angiographic vasospasm. SPECT showed hypoperfusion in 22 out of 25 patients. CT predicted CVS in 8 of these 22 patients. Our study shows that brain perfusion SPECT is a non-traumatic, non-invasive, non-allergic, inexpensive method for the prediction of cerebral vasospasm. We conclude that brain SPECT with Tc-99m HM-PAO is an accessible technique that can demonstrate varying degrees of regional tissue hypoperfusion in patients with delayed ischemic deficits due to CVS following SAH.     

Association of an endogenous inhibitor of nitric oxide synthase with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage

OBJECT: Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) may be evoked by the decreased availability of nitric oxide (NO). Increased cerebrospinal fluid (CSF) levels of asymmetric dimethyl-L-arginine (ADMA), an endogenous inhibitor of NO synthase (NOS), have been associated with the course and degree of cerebral vasospasm in a primate model of SAH. In this study, the authors sought to determine if similar changes in CSF ADMA levels are observed in patients with SAH, and whether these changes are associated with NO and NOS metabolite levels in the CSF and the presence of cerebral vasospasm. METHODS: Asymmetric dimethyl-L-arginine, L-arginine, L-citrulline, and nitrite levels were measured in CSF and serum samples collected during the 21-day period after a single aneurysmal SAH in 18 consecutive patients. Samples were also obtained in a control group consisting of seven patients with Chiari malformation Type I and five patients with spontaneous intracerebral hemorrhage without SAH. Vasospasm, defined as a greater than 11% reduction in the anterior circulation vessel diameter ratio compared with the ratio calculated from the initial arteriogram, was assessed on cerebral arteriography performed around Day 7. RESULTS: In 13 patients with SAH, arteriographic cerebral vasospasm developed. Cerebrospinal fluid ADMA levels in patients with SAH were higher than in those in the control group (p < 0.001). The CSF ADMA level remained unchanged in the five patients with SAH without vasospasm, but was significantly increased in patients with vasospasm after Day 3 (6.2 +/- 1.7 microM) peaking during Days 7 through 9 (13.3 +/- 6.7 microM; p < 0.001) and then gradually decreasing between Days 12 and 21 (8.8 +/- 3.2 microM; p < 0.05). Nitrite levels in the CSF were lower in patients with vasospasm compared to patients without vasospasm (p < 0.03). Cerebrospinal fluid ADMA levels positively correlated with the degree of vasospasm (correlation coefficient [CC] = 0.88, p = 0.0001; 95% confidence interval [CI] 0.74-0.95) and negatively correlated with CSF nitrite levels (CC = -0.55; p = 0.017; 95% CI -0.81 to -0.12). CONCLUSIONS: These results support the hypothesis that ADMA is involved in the progression of cerebral vasospasm. Asymmetric dimethyl-L-arginine and its metabolizing enzymes may be a future target for treatment of cerebral vasospasm after SAH.