Pharmacological Studies of the Pathogenesis of Cerebral Vasospasm Following Subarachnoid Hemorrhage and its Treatment.

蛛网膜下腔出血后脑血管痉挛发病机制及治疗的药理学研究。

基本信息

批准号：
62480304
负责人：
SASAKI Tomio
金额：
$ 3.52万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

The purpose of the present studies were (1)to develop an in vitro vascular perfusion system and (2)to evaluate the vascular responses to various vasoactive agents when those were applied intraluminally and extraluminally.1)Comparison of the effects by intraluminal and extraluminal administration of vasoactive agents:Intraluminal administration of KCl produced significantly stronger constrictions of rabbit basilar arteries than the extraluminal administration. Serotonin-induced contraction was the same with either application.Hemoglobin-induced contraction was stronger with extraluminal application than with intraluminal application. However, no statistical difference was observed. Extraluminal administration of endothelin induced a little bit stronger contractions than the intraluminal administration.2)Comparison of intraluminal and extraluminal inhibitory effects of hemoglobin on endothelium-dependent relaxation:Hemoglobin's inhibition of Ach- and ATP- induced relaxation was significantly greater with intraluminal than with extraluminal application.3)Relationship between inhibitory effects of cerebrospinal fluids(CSF) on endothelium-dependent relaxation and cerebral vasospasm:CSFs collected from SAH patients with vasospasm showed significantly stronger inhibition of endothelium-dependent relaxation than those collected from the patients without vasospasm.4)Species differences of endothelium-dependent relaxation:In canine basilar arteries with intact endothelium, ATP induced strong relaxations of the-5-HT-induced contraction while Ach did not induce marked relaxations.In rabbit basilar arteries both ATP and Ach induced marked relaxations of the 5-HT-induced contraction.In monkey and human cerebral arteries either ATP or A23187 relaxed markedly the PGF<@D2@>Dd2 alpha-induced contraction.

本研究的目的是（1）开发体外血管灌注系统，（2）评估管腔内和管外应用各种血管活性药物时血管的反应。1）管腔内和管外给药效果的比较血管活性药物的作用：腔内给予KCl比腔外给予对兔基底动脉产生明显更强的收缩作用。血清素诱导的收缩与任一应用相同。腔外应用的血红蛋白诱导的收缩比腔内应用更强。然而，没有观察到统计学差异。管腔外给予内皮素引起的收缩比管腔内给予稍强。2)管腔内和管腔外血红蛋白对内皮依赖性舒张的抑制作用比较:管腔内血红蛋白对Ach和ATP诱导的舒张的抑制作用明显强于管腔外。应用3)脑脊液(CSF)对内皮依赖性舒张的抑制作用与脑神经功能的关系血管痉挛：有血管痉挛的SAH患者的脑脊液对内皮依赖性舒张的抑制作用明显强于无血管痉挛患者的脑脊液。4）内皮依赖性舒张的物种差异：在内皮完整的犬基底动脉中，ATP诱导内皮依赖性舒张的强烈抑制作用。 5-HT 引起收缩，而 Ach 不引起明显的松弛。在兔基底动脉中，ATP 和 Ach 均引起明显的松弛。 5-HT诱导的收缩的松弛。在猴子和人的脑动脉中，ATP或A23187显着松弛PGF<@D2@>Dd2α诱导的收缩。