PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASMS
慢性脑血管痉挛的病理生理学
基本信息
- 批准号:3411517
- 负责人:
- 金额:$ 22.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1988
- 资助国家:美国
- 起止时间:1988-04-01 至 1994-08-31
- 项目状态:已结题
- 来源:
- 关键词:Macaca fascicularis calcium calcium channel cardiovascular disorder prevention catalase cerebral aneurysm cerebral artery cerebral hemorrhage cerebral ischemia /hypoxia cerebroangiography cytoskeleton disease /disorder model electron microscopy fluorescence microscopy fluorescent dye /probe free radical oxygen immunocytochemistry laboratory rabbit laboratory rat membrane lipids monoclonal antibody oxyhemoglobin pathologic process protein kinase C statistics /biometry urokinase vascular smooth muscle vasospasm voltage /patch clamp
项目摘要
About 30,000 North Americans have rupture of an intracranial aneurysm
each year. Because aneurysmal rupture, among all forms of intracranial
bleeding, almost uniquely deposits a large volume of blood clot on the
adventitial side of the basal conducting arteries, it is frequently the
cause of a delayed onset, long-lasting arterial constriction known as
vasospasm. Vasospasm can be so severe that the vessels may actually be
occluded and distal ischemia can result with attendant delayed infarction
- the second stroke. About two-thirds of ruptured aneurysm patients will
show moderate to severe degrees of angiographic vasospasm if subjected to
angiography a week or so after the initial hemorrhage. About half of
these patients will develop clinical signs of delayed ischemia. The
death rate from this phenomenon has fallen steadily in recent years with
the widespread avoidance of dehydration and antifibrinolytic agents. In
addition, calcium antagonists, hypertension and hypervolemia may have
exerted a beneficial effect. Currently, however, about 15% of patients
will still die or be severely damaged by vasospasm. Evidence of ischemic
cerebral infarction is noted in about 30% of the fatal cases of
aneurysmal ruptures if they survive past the initial few days.
Our long-term objectives are:
(1) prevention of vasospasm after subarachnoid hemorrhage;
(2) the successful treatment of established vasospasm.
The specific aims of the project are to determine:
(1) time course of cytoskeletal changes in arterial walls of cerebral
arteries after subarachnoid hemorrhage in monkeys; (2) pathogenesis and
prevention of oxyhemoglobin-induced cerebral vasospasm in monkeys; (3)
biochemical changes in arterial vessel wall as vasospasm develops and
abates; (4) time course of intracellular free calcium concentration
changes in cultured vascular smooth muscle cells following prolonged
exposure to oxyhemoglobin and if the mechanism of calcium entry is
sensitive to normal antagonists of calcium channels; (5) role of
activation of protein kinase C in production of cerebrovascular spasm;
(6) the source of increased intracellular calcium correlated with damage
by oxyhemoglobin; (7) if free radicals damage isolated cerebrovascular
smooth muscle cells primarily from the inside or outside; (8) whether
free radicals damage lipid components of surface membrane or ion
channels; (9) if transluminal balloon dilatation of spastic primate
cerebral arteries results in immediate and enduring improvement in vessel
caliber and whether there is any adverse structural change in the
arterial wall; (10) if intrathecal urokinase can prevent chronic cerebral
vasospasm in a primate model.
大约 30,000 名北美人患有颅内动脉瘤破裂
每年。 因为动脉瘤破裂是所有形式的颅内动脉瘤中
出血,几乎是唯一一种在皮肤上沉积大量血凝块的情况
基底传导动脉的外膜侧,通常是
延迟发作、持久的动脉收缩的原因,称为
血管痉挛。 血管痉挛可能非常严重,以至于血管实际上可能
闭塞性和远端缺血可导致迟发性梗塞
- 第二次中风。 大约三分之二的动脉瘤破裂患者会
如果接受血管造影,显示中度至重度血管痉挛
初次出血后一周左右进行血管造影。 大约一半
这些患者会出现迟发性缺血的临床症状。 这
近年来,这种现象造成的死亡率稳步下降
普遍避免脱水和抗纤溶药物。 在
此外,钙拮抗剂、高血压和血容量过多可能会导致
发挥了有益的作用。 但目前约有 15% 的患者
仍然会死亡或因血管痉挛而严重受损。 缺血的证据
脑梗死占死亡病例的 30%
如果动脉瘤破裂在最初几天内存活下来。
我们的长期目标是:
(1)预防蛛网膜下腔出血后血管痉挛;
(2)成功治疗既定的血管痉挛。
该项目的具体目标是确定:
(1)脑动脉壁细胞骨架变化的时间过程
猴子蛛网膜下腔出血后的动脉; (2)发病机制及
预防猴氧合血红蛋白引起的脑血管痉挛; (3)
随着血管痉挛的发展,动脉血管壁发生生化变化
减弱; (4)细胞内游离钙浓度的时程
长时间培养后血管平滑肌细胞发生变化
暴露于氧合血红蛋白以及钙进入的机制是否
对钙通道的正常拮抗剂敏感; (5)作用
蛋白激酶C的激活导致脑血管痉挛;
(6)与损伤相关的细胞内钙增加的来源
通过氧合血红蛋白; (7)自由基是否损伤离体脑血管
平滑肌细胞主要来自内部或外部; (8) 是否
自由基破坏表面膜或离子的脂质成分
渠道; (9)痉挛灵长类动物腔内球囊扩张术
脑动脉导致血管立即和持久的改善
口径以及是否存在不利的结构变化
动脉壁; (10)鞘内注射尿激酶能否预防慢性脑病
灵长类动物模型中的血管痉挛。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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