Variations between individuals in cerebrovascular responsiveness

1. Despite extensive research no explanation has been put forward to account for the fact that cerebral arterial spasm complicates the course of disease of many but not all patients suffering from rupture of an intracranial aneurysm. Although vasoactive material in hemorrhagic cerebrospinal fluid (CSF) most probably is of major importance in the pathophysiology of delayed cerebral vasospasm, recent studies have failed to demonstrate a correlation between CSF vasoconstrictor activity and the development of delayed cerebral vasospasm. 2. In the present study the reactivity of isolated human pial arteries to various vasoactive agents [prostaglandin F2 alpha, noradrenaline, serotonin, human plasma and CSF from patients with aneurysmal subarachnoid hemorrhage (SAH)] was investigated. 3. There was a very marked variability in the spectrum of responses between arteries from different individuals with regard to the contractile responses to plasma, hemorrhagic CSF and amines. On the other hand, the contractions produced by prostaglandin F2 alpha and potassium were consistent. 4. The markedly individual profile in terms of reactivity toward vasoactive substances emphasizes the importance of a human cerebral vessel wall factor and may explain the capricious occurrence of cerebral vasospasm after aneurysmal SAH.     

Alpha-adrenoceptors in human and animal cerebral arteries: alterations after sympathetic denervation and subarachnoid hemorrhage

Vasospasm of cerebral arteries in patients with subarachnoid hemorrhage frequently presents severe clinical problems resulting from cerebral ischemia, but the pathogenesis of vasospasm is still poorly understood. The contractile response of human cerebral arteries to noradrenaline is larger than the responses in other species. Neurogenic factors controlling brain circulation may play an important role in pathological conditions such as subarachnoid hemorrhage. Motohatsu Fujiwara and colleagues review species variations of alpha-adrenoceptors in cerebral arteries and their alterations after surgical sympathectomy. They compare these changes to those occurring in human cerebral arteries following subarachnoid hemorrhage and discuss their relationship to vasospasm.     

Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: their relevance to cerebral arterial spasm in man.

1 Isolated strips of human or baboon basilar, middle cerebral, vertebral or common carotid arteries were set up in an isolated organ bath or in a superfusion cascade system. 2 These arteries relaxed to prostacyclin but contracted to prostaglandin endoperoxide (PGH2). 3 Human and baboon isolated arteries also generated prostacyclin from exogenous endoperoxide (PGH2). 4 Human arteries generated prostacyclin 36 h post-mortem but not 40 h post-mortem. The biologically generated prostacyclin relaxed the basilar artery and overcame the contractile effects of PGH2. 5 Thromboxane A2-like activity generated during human platelet aggregation by arachidonic acid caused contractions of the human basilar artery. 6 Prostacyclin reversed contractions of human basilar arteries caused by an unidentified vasoconstrictor factor in cerebrospinal fluid obtained from patients with cerebral arterial vasospasm after subarachnoid haemorrhage following rupture of cerebral arterial aneurysms. 7. The above vasospasm may be due at least in part to disordered physiological control of the calibre of cerebral arteries caused by diminished synthesis of prostacyclin.     

Effect of nimodipine, a calcium antagonist, on cerebral vasospasm after subarachnoid hemorrhage in cats

Effect of a calcium antagonist, isopropyl-(2-methoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5- pyridinedicarboxylate (nimodipine) on the cerebral vasospasm after experimental subarachnoid hemorrhage (SAH) was studied in ten adult cats. The vasospasm was induced by injecting of 0.2-0.3 ml fresh autologous whole blood into the cisterna magna. Diameter of pial vessels was continuously measured by means of the vidicon camera system developed in our laboratory. Intravenous administration of nimodipine (0.1 mg/kg) 20-30 min after SAH resulted in a complete disappearance of the spasm with the reduction of blood pressure. The dilatory response was more marked in the smaller arteries (less than 100 microns) than in the larger ones (greater than or equal to 100 microns). Administration of smaller dose of nimodipine (0.01 mg/kg) also produced dilation of the pial vessels, although the effect was less remarkable in the smaller arteries. These data suggest that nimodipine might be useful in the treatment of the cerebral vasospasm after SAH. The mechanism underlying the action of nimodipine was discussed.     

Role of MAPK in cerebral vasospasm

Cerebral vasospasm is the major cause of mortality and morbidity in patients of subarachnoid hemorrhage. Despite intensive studies during the past five decades, the signaling pathways in cerebral arteries that lead to the pathological contraction remain elusive. The complex nature of cerebral vasospasm requires a complex signaling pathway or a group of pathways that may need to interact to initiate and maintain vasospasm. This review explores the possibility that mitogen-activated protein kinase is the elusive signaling pathway responsible for cerebral vasospasm.     

Pharmacological characterization of postjunctional alpha-adrenoceptors in cerebral arteries from the sheep.

1. The responsiveness to noradrenaline was characterized in cerebral arteries from the sheep, since this species was large enough to permit a comparison of arteries from different parts of the cerebral vasculature. 2. Noradrenaline caused contraction of the basilar artery, middle cerebral artery and small pial arteries by stimulation of alpha 1-adrenoceptors. 3. The maximum contraction to noradrenaline was small in the basilar artery (28% of the 5-hydroxytryptamine (5-HT) maximum) but larger in the middle cerebral artery (78% of the 5-HT maximum) and pial artery (92% of the 5-HT maximum) of the sheep. 4. Cocaine (10 microM) potentiated noradrenaline-induced contractions in the sheep middle cerebral artery but not in the sheep basilar artery. 5. The noradrenaline contraction, relative to the 5-HT contraction, was not affected by removal of the endothelium in either the sheep basilar or middle cerebral artery. 6. The results showed a variation within the sheep cerebral vasculature in the response to noradrenaline which cannot be explained by regional differences in alpha-adrenoceptor subtypes, noradrenaline uptake mechanisms or endothelial function.     

尼莫地平2种给药途径治疗蛛网膜下腔出血后脑血管痉挛的疗效观察

目的:观察尼莫地平2种给药途径治疗蛛网膜下腔出血后脑血管痉挛的疗效。方法:68例原发性蛛网膜下腔出血患者,随机分为静脉尼莫地平组和口服尼莫地平组,通过经颅多普勒检测2种给药途径治疗脑血管痉挛后脑血流速度的变化,观察血管痉挛发生率、再出血率及死亡率,评价2种给药途径的疗效。结果:2组患者治疗后21d大脑中动脉血流速度明显改善,同治疗前比较,差异有显著性(P<0.05),治疗后21d神经功能缺损评分有显著性差异(P<0.05),且静脉尼莫地平组神经功能改善最佳,但2组无显著性差异(P>0.05);2组患者脑血管痉挛发生率、死亡率及再出血发生率明显降低,组间比较无显著性差异(P>0.05)。2组不良反应均较轻微。结论:尼莫地平治疗蛛网膜下腔出血疗效确切,口服及静脉给药疗效相当。     

蛛网膜下腔出血后迟发性脑血管痉挛中 TNF-α和NF-кB 的表达变化

目的：检测蛛网膜下腔出血（以下简称 SAH）后迟发性脑血管痉挛中TNF-α和NF-кB的表达变化。方法56只中国白兔随机分成3组：对照组（ n ＝8）：不做枕大池穿刺注血,处死;SAH组（ n ＝24）：在第0天和第2天分二次枕大池注射自体动脉血,分别在第1次注血后第4天、第7天和第14天分三批处死,每组8只;假手术组（ n＝24）：只做枕大池穿刺不注血,第4天、第7天和第14天处死,每组8只。通过计算动脉口径比判断基底动脉痉挛程度,使用免疫组化和免疫蛋白印迹的方法检测迟发性脑血管痉挛中TNF-α和NF-кB的表达变化。结果枕大池注血方法可以造成SAH后迟发性脑血管痉挛模型。 NF-κB 和 TNF-α在注血后第4天表达开始增加（ P ＜0．01）,在第7天达到最高值（ P ＜0．01）,第14天降到对照组水平。结论蛛网膜下腔出血后迟发性脑血管痉挛中NF-κB及 TNF-α表达增加,炎症反应在此过程中起着重要作用。     

西洛他唑治疗动脉瘤性蛛网膜下腔出血的作用机制和临床研究进展

动脉瘤性蛛网膜下腔出血后的迟发性脑缺血是患者严重残疾甚至死亡的主要原因，迟发性脑缺血形成的主要危险因素是脑血管痉挛。西洛他唑是磷酸二酯酶Ⅲ的选择性抑制剂，可舒张血管、抗脂质过氧化、抗血管炎症因子、抑制基底动脉的表型转化和内皮损伤以及抑制腱糖蛋白-C。近年来一系列临床试验表明西洛他唑单用或者联合使用可有效治疗动脉瘤性蛛网膜下腔出血后的脑血管痉挛，进而改善迟发性脑缺血。回顾了西洛他唑在动脉瘤性蛛网膜下腔出血中的作用机制和临床研究，为进一步研究西洛他唑在动脉瘤性蛛网膜下腔出血中的应用提供参考。     

蛛网膜下腔出血行腰椎穿刺置管持续稳压引流的疗效分析

目的探讨腰椎蛛网膜下腔置管持续引流对蛛网膜下腔出血(SAH)的疗效。方法:对63例SAH患者进行治疗:治疗组(33例)实施腰椎蛛网膜下腔置管持续流脑脊液,对照组(30例)行间断腰椎穿刺放脑脊液。结果:治疗组头痛或轻程度,痊愈率明显优于对照组,脑血管痉挛、脑积水发生率明显低于对照组,未增加再出血、脑疝发生率及病死率。结论:腰椎蛛网膜下腔置管持续稳压引流脑脊液是一种安全、有效的治疗SAH的方法。     

Enhanced reactivity to vasopressin in rat basilar arteries during vasospasm after subarachnoid hemorrhage

Subarachnoid hemorrhage increases the plasma level of vasopressin, a well-known vasoconstrictor. We examined the sensitivity to vasopressin in rat basilar artery after subarachnoid hemorrhage using a rat subarachnoid hemorrhage model. Vasospasm was observed 1-2 days after subarachnoid hemorrhage induction, and the contractile response to vasopressin in rat basilar arteries was assessed. The concentration-response curve for vasopressin in subarachnoid hemorrhage (1 day) rats shifted leftward compared with that of control rats. The concentration-response curve for vasopressin V(1) receptor agonist also shifted leftward and upward compared with that of control rats. The concentration-response curve for vasopressin was inhibited not by vasopressin V(2) receptor antagonist but by vasopressin V(1) receptor antagonist. Thus, it was demonstrated that the vasoconstricting effect of vasopressin was significantly enhanced in the vasospasm phase after subarachnoid hemorrhage.     

枕大池注入硫酸镁对兔蛛网膜下腔出血后脑血管痉挛的逆转及脑保护作用

目的:研究枕大池注入硫酸镁注射液是否能逆转兔蛛网膜下腔出血后脑血管痉挛以及脑组织损伤。方法:采用兔一次性注血的方法建立蛛网膜下腔出血模型。将30只新西兰大白兔随机分为3组:假手术组、模型组和MgSO4组。前二组于术后24h枕大池注入0.1mL.kg-1生理盐水,后一组注入0.1mL.kg-14%MgSO4。48h后处死兔取基底动脉以及海马组织行病理检查,测定基底动脉管腔横切面积和海马CA1区正常神经元密度。结果:以基底动脉管腔横切面积及海马CA1区正常神经元密度为指标,模型组低于假手术组和MgSO4组(P<0.01),而后二组比较无明显差异(P>0.05)。结论:枕大池注入硫酸镁注射液可能具有逆转兔蛛网膜下腔出血后脑血管痉挛以及脑血管痉挛所致海马神经元损伤作用。     

Penetration of cefotaxime into human cerebrospinal fluid

The penetration of cefotaxime (CTX) into the cerebrospinal fluid (CSF) was monitored to evaluate the prophylactic efficacy of the drug against post-craniotomy infections. Doses ranged from 1 to 2 g were administered to patients with subarachnoid hemorrhage due to the rupture of cerebral aneurysm, traumatic cerebral contusion, or subdural edema accompanied by intracerebral hemorrhage, by intravenous drip infusion over a period of 30 or 60 minutes. CTX readily entered the CSF with concentrations exceeding MICs against the major pathogens occurring after craniotomy. CTX proved to be effective in the prevention of post-craniotomy infections in noninflammatory situations, especially after surgery in the case of cerebral traumas or subarachnoid hemorrhage.     

尼莫同治疗蛛网膜下腔出血引起脑血管痉挛的护理研究

目的探讨尼莫同治疗蛛网膜下腔出血诱发脑血管痉挛的护理效果。方法选取本院2010年5月至2013年5月蛛网膜下腔出血诱发脑血管痉挛患者74例,行尼莫同治疗,随机分为两组,37例患者行常规护理为对照组,37例患者行护理干预为观察组,比较两组患者脑血管痉挛复发情况、头痛持续时间、不良反应情况。结果观察组脑血管痉挛复发率、头痛持续时间、不良反应发生率均明显小于对照组,差异均显著(P<0.05)。结论尼莫同治疗蛛网膜下腔出血诱发脑血管痉挛时,护理干预可明显缩短患者的头痛持续时间,降低脑血管痉挛复发率和不良反应发生率。     

小牛血清去蛋白注射液联合尼莫地平治疗创伤性蛛网膜下腔出血后的脑血管痉挛

目的：探讨小牛血清去蛋白注射液联合尼莫地平防治创伤性蛛网膜下腔出血（tSAH）后脑血管痉挛的疗效.方法：将80例创伤性蛛网膜下腔出血患者随机分为治疗组和对照组各40例,两组在常规治疗基础上,均应用尼莫地平注射液10 mg/d静脉泵入（5 ml/h）,1次/d;治疗组加用小牛血清去蛋白注射液1200 mg加入氯化钠注射液250 ml静脉滴注;两组连续治疗14 d.对比两者治疗脑血管痉挛的差异性,用经颅多普勒检测脑血流,并进行统计学分析.结果：治疗组的脑血管痉挛发生率明显低于对照组（P〈0.05）,治疗组的大脑前动脉、大脑中动脉、大脑后动脉的脑血管收缩峰流速低于对照组（P〈0.05）.结论：小牛血清去蛋白注射液联合尼莫地平防治 tSAH后脑血管痉挛疗效优于单纯应用尼莫地平.     

尼莫地平对蛛网膜下腔出血后脑血管痉挛模型兔血浆BNP和ET-1表达水平的影响

目的探讨尼莫地平（ND）对蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）兔血浆脑利钠肽（BNP）和内皮素-1（ET-1）含量的影响。方法采用枕大池二次注血法建立兔CVS模型。将40只成年日本大耳白兔随机均分为单纯SAH组（SAH组）和ND治疗组（ND组）。观察两组实验动物的食量及神经功能评分,分别采用酶联免疫吸附测定法（ELISA）和放射免疫法（R IA）检测血浆BNP、ET-1含量,并用经颅多普勒超声（TCD）动态观察两组家兔术前1天和术后第1、4、7、10、14天的基底动脉（BA）血流速度。结果两组家兔注血后第1天血浆BNP水平开始升高（P〈0.05）,ET-1虽较术前有所升高但无统计学意义（P〉0.05）,4-7 d BNP、ET-1均达到高峰（P〈0.05-0.01）,且随着时间的推移有逐渐降低的趋势;ND组BNP及ET-1含量增加的程度明显低于SAH组（P〈0.05-0.01）,但仍显著高于术前对照组（P〈0.05）;两组家兔术后BA血流速度的动态变化趋势与其血浆BNP、ET-1的变化基本一致。结论 SAH后血浆BNP、ET-1含量增多参与了CVS的过程,与CVS的发生、发展密切相关;ND可降低SAH后CVS时血浆BNP、ET-1的水平。     

Effects of pinacidil on cerebral and mesenteric arteries —influence of the endothelium

Summary The effect of pinacidil on the contractile response to stepwise increases of the extracellular K⁺ concentration ([K⁺]₀) was investigated in isolated segments of human pial and mesenteric arteries and rabbit basilar and mesenteric arteries. The [K⁺]_O eliciting half maximum contraction (EC₅₀) was lower in human pial (18 mM) and rabbit basilar (27 mM) arteries than in human (33 mM) and rabbit (32 mM) mesenteric arteries, respectively. The -adrenoceptor blocker, prazosin, increased the EC₅₀ value for K⁺ from 27 to 40 mM and reduced the maximum response in rabbit mesenteric arteries, but had no effect on the K⁺-induced contraction in rabbit basilar arteries, indicating a substantial noradrenergic component of the K⁺ response in the former arteries. Removal of the endothelium decreased the EC₅₀ value for K⁺ from 27 to 15 mM in rabbit basilar arteries, whereas the K⁺ sensitivity was unaffected in rabbit mesenteric arteries. Pinacidil shifted the K⁺ concentration-response curve to the right in human and rabbit cerebral and mesenteric arteries. In rabbit basilar arteries, but not in mesenteric arteries, the shift was larger in the absence than in the presence of an intact endothelium. When endothelium-denuded rabbit arteries were compared, the inhibitory effect of pinacidil was larger in basilar than in mesenteric arteries. Thus, pinacidil inhibits K⁺-induced contractions in both cerebral and mesenteric arteries, but appears to act preferentially on endothelium-denuded rabbit basilar arteries. Provided that endothelial damage and depolarization-induced vasoconstriction are of pathophysiological importance in cerebrovascular disorders such as stroke and cerebral ischemia secondary to vasospasm after subarachnoid hemorrhage, pinacidil may have a therapeutic potential. Correspondence to E. D. Hogestatt at the above address     

Prevention of delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage

The delayed cerebral vasoconstriction known as cerebral vasospasm remains a significant cause of permanent neurological deficit and death following aneurysmal subarachnoid hemorrhage despite the best current medical therapies. The mechanism of cerebral vasospasm remains unknown. Several new drugs have been tested in animal models of subarachnoid hemorrhage, and these experimental studies have contributed to a better understanding of the potential mechanisms that lead to cerebral vasospasm. In this article, the authors highlight recent advances in the various treatment procedures for delayed cerebral vasospasm following subarachnoid hemorrhage. (c) 2001 Prous Science. All rights reserved.