PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASMS

慢性脑血管痉挛的病理生理学

• 批准号: 2265742
• 负责人: BRYCE K WEIR
• 金额: $ 12.54万
• 依托单位: UNIVERSITY OF ALBERTA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265742
• 关键词: PATHOPHYSIOLOGY; CHRONIC; CEREBRAL; VASOSPASMS

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. 因为在所有形式的颅内动脉瘤中， 出血，几乎是唯一的沉积大量的血凝块上的 在基底传导动脉的外膜侧，它经常是 延迟发作的原因，长期持续的动脉收缩称为 血管痉挛 血管痉挛可能非常严重， 闭塞和远端缺血可导致伴随的延迟性梗死 - 第二次中风。 大约三分之二的动脉瘤破裂患者将 显示中度至重度血管造影性血管痉挛，如果 在出血后一周左右进行血管造影。 的一半左右 这些患者将出现延迟性局部缺血的临床体征。 的 近年来，这一现象造成的死亡率稳步下降， 广泛避免脱水和抗纤维蛋白溶解剂。 在 此外，钙拮抗剂、高血压和高血容量症可能 产生了有益的影响。 目前，约有15%的患者 还是会因为血管痉挛而死亡或严重受损 缺血性证据 脑梗塞在约30%的致命病例中被注意到， 如果它们能撑过最初的几天，就会出现巨大的破裂。 我们的长期目标是： (1)预防蛛网膜下腔出血后血管痉挛; (2)血管痉挛的成功治疗 该项目的具体目标是确定： (1)脑动脉壁细胞骨架变化的时程 猴蛛网膜下腔出血后的动脉;（2）发病机制和 预防氧化血红蛋白诱导的猴脑血管痉挛;（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 培养的血管平滑肌细胞在长时间 暴露于氧合血红蛋白，如果钙进入的机制是 对正常钙通道拮抗剂敏感;（5） 蛋白激酶C的激活与脑血管痉挛的发生有关; (6)细胞内钙增加的来源与损伤相关 氧合血红蛋白;（7）如果自由基损伤孤立脑血管 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 通道;（9）如果痉挛灵长类动物的经腔球囊扩张 脑动脉导致血管立即和持久的改善 口径和是否有任何不利的结构性变化， （10）鞘内注射尿激酶是否能预防慢性脑梗死 血管痉挛的灵长类动物模型。