PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASMS

每10万人中约有10例新发动脉瘤破裂病例 可能每年都会出现。这类患者的平均年龄 只有50多年了。而15%或20%的患者会当场死亡 现在，大多数人都活了下来，可以住院治疗。如果这些病人这样做了 不会死于他们出血的最初破坏性影响 然后不得不面对各种威胁生命的延迟危险 包括最重要的慢性延迟性脑缺血 血管痉挛和再出血。据估计， 有效的血管痉挛治疗可能挽救北方5000人的生命 每年在美国。 在过去的十年里，在医疗方面取得了进展 股骨头痉挛所致低血流量的处理 较大的基底传导动脉与周围环境相连 血块。首先，通过确保最优来增加区域流量 循环血容量、红细胞压积、血压、粘度和 心输出量。其次，神经结果一直是 通过使用钙拮抗剂进行改进，这种拮抗剂通过 除预防大面积血管痉挛外的其他机制 传导动脉-它们可以扩张较小的血管或提供 具有直接神经元保护作用的元素。 然而，这些发展并没有直接攻击基本的 脑血管痉挛的问题。血管内皮细胞的病理生理链 事件及其生化关联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。而当 在48小时内完全清除刺激性血块 在灵长类动物模型中防止血管痉挛的发展，完全 对于病人来说，切除是不可能的，为此进行了积极的尝试 会带来额外的手术风险。一种药物干预 停止最终导致痉挛的化学反应 如果出现以下情况，动脉节段将比手术预防更可取 它没有明显的副作用，如全身性 低血压。 建议对该化合物的化学、药理和 慢性阻塞性肺疾病发生发展过程中的生理变化 直接应用血栓治疗灵长类动物模型中的血管痉挛 手术暴露的基底血管和序贯采样 动脉和脑组织。治疗策略将应用于 其机制被阐明，并作为新的和有希望的药物和 介绍了递送技术。

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.