PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASMS

慢性脑血管痉挛的病理生理学

• 批准号: 3411516
• 负责人: BRYCE K WEIR
• 金额: $ 12.32万
• 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 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3411516
• 关键词: Macaca; aneurysm; angiography; antithrombin III; aspirin; calcium channel blockers; cardiovascular pharmacology; cerebral ischemia /hypoxia; cerebrovascular disorder diagnosis; disease /disorder model; drug metabolism; electrical potential; free radicals; glucose metabolism; heparin; hyperoxia; magnetic resonance imaging; pathologic process; prostacyclins; ultrasound blood flow measurement; vascular smooth muscle; vasospasm

About 10 new cases of ruptured aneurysm per 100,000 population may be anticipated each year. The average age of such patients is just over 50 years. While 15 or 20 % of sufferers die instantly the majority now survive to be hospitalized. If these patients do not die of the initial disruptive effects of their hemorrhage they then have to face a variety of life threatening delayed hazards including most importantly delayed ischemia from chronic vasospasm as well as rebleeding. It has been estimated that an effective therapy for vasospasm could save 5,000 lives in North America per year. In the past decade there has been progress in the medical management of the low blood flow resulting from the spasm of the larger basal conducting arteries consequent to the surrounding clot. Firstly, regional flow is increased by ensuring optimal circulating blood volume, hematocrit, pressure, viscosity and cardiac output. Secondly, neurological outcome has been improved by the use of calcium antagonists which operate by a mechanism other than the prevention of vasospasm in the large conducting arteries-they may dilate smaller vessels or provide an element of direct neuronal protection. These developments have not however directly attacked the basic problem of cerebral vasospasm. The pathophysiological chain of events and its biochemical correlates are largely unknown so that rational, direct therapy or prophylaxis is difficult. While complete removal of the inciting blood clot wihin 48 hours prevents vasospasm from developing in the primate model, total removal is not possible in patients and vigorous attempts at this carries additional surgical risks. A pharmacological intervention to halt the chemical reactions which ultimately lead to a spastic arterial segment would be preferable to the surgical prophylaxis if it were without significant side effects such as systemic hypotension. It is proposed to characterize the chemical, pharmacological and physiological changes associated with the development of chronic vasospasm in a primate model using direct clot application to the surgically exposed basal vessels sand sequential sampling of arteries and brain tissue. Treatment strategies will be applied as the mechanism is elucidated and as new and promising drugs and delivery techniques are introduced.

每 10 万人中约有 10 例新发动脉瘤破裂病例 每年都可以预期。 此类患者的平均年龄 才50多年。 而 15% 或 20% 的患者会立即死亡 大多数人现在都存活下来并住院治疗。 如果这些患者这样做 他们并没有死于失血的最初破坏性影响 然后还要面对各种威胁生命的迟来的危险 包括最重要的慢性迟发性缺血 血管痉挛以及再出血。 据估计，一个 有效治疗血管痉挛可以挽救北方 5,000 人的生命 美国每年。 近十年来，医学取得了长足的进步 治疗痉挛引起的低血流量 周围较大的基底传导动脉 凝块。 首先，通过确保最优来增加区域流量 循环血量、血细胞比容、压力、粘度和 心输出量。 其次，神经系统结果 通过使用钙拮抗剂来改善，钙拮抗剂的作用是 除了预防大血管痉挛以外的机制 传导动脉——它们可以扩张较小的血管或提供 直接神经元保护的要素。 然而，这些发展并没有直接攻击基本的 脑血管痉挛的问题。 病理生理链 事件及其生化相关性在很大程度上是未知的，因此 合理、直接的治疗或预防是困难的。 尽管 48小时内完全清除刺激性血凝块 防止灵长类动物模型中发生血管痉挛，总计 在患者身上不可能去除，并且对此进行了大力尝试 会带来额外的手术风险。 药物干预 停止最终导致痉挛的化学反应 如果出现以下情况，动脉段治疗优于手术预防 它没有明显的副作用，例如系统性的 低血压。 建议对化学、药理学和 与慢性病发展相关的生理变化 使用直接将凝块应用到灵长类动物模型中的血管痉挛 手术暴露的基底血管和连续取样 动脉和脑组织。 治疗策略将应用为 该机制已被阐明，并作为新的有前途的药物和 介绍了交付技术。