PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASM

慢性脑血管痉挛的病理生理学

• 批准号: 2265744
• 负责人: BRYCE K WEIR
• 金额: $ 26.54万
• 依托单位: UNIVERSITY OF CHICAGO
• 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 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265744
• 关键词: Mammalia; antispasmodic agents; calcium channel; calcium flux; cardiovascular disorder prevention; cerebral aneurysm; cerebral hemorrhage; cerebral ischemia /hypoxia; cerebroangiography; disease /disorder model; immunocytochemistry; neuroprotectants; oxyhemoglobin; plasminogen activator; potassium channel; urokinase; vascular endothelium; vascular smooth muscle; vasospasm; voltage /patch clamp

DESCRIPTION (Investigator's Abstract): About 30,000 North Americans have rupture of an intracranial aneurysm each year. Because aneurysm 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 frequency 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 he 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: (I) The prevention of vasospasm after subarachnoid hemorrhage (2) The successful treatment of established vasospasm. The specific aims are: 1)To determine which component or components of oxyhemoglobin cause vasospasm. (2) To determine the efficacy of endothelia antagonists in treatment of vasospasm after subarachnoid hemorrhage. (3) To compare the efficacy of tissue-type plasminogen activator and urokinase for lysis of subarachnoid clot and prevention of vasospasm. (4) To investigate calcium homeostasis in the cellular mechanisms of vasospasm by monitoring Ca?+ dependent K+ channels. (5) To characterize the calcium channels in cerebral vascular smooth muscle cells and determine how they are affected by blood components. (6) To study the effect of blood components on potassium channels of cerebrovascular smooth muscle cells. (7) To test the actions of blood components on ion channels of cerebral endothelium.

描述(调查人员摘要)：大约30,000名北美人 每年都会有一个颅内动脉瘤破裂。因为动脉瘤破裂， 在所有形式的颅内出血中，几乎唯一的一种是 基底部外膜一侧有大量血块。 传导动脉，它经常是起病延迟的原因，长期- 持续性动脉收缩称为血管痉挛。血管痉挛可以是这样的 严重的是血管实际上可能闭塞，远端缺血可以 结果伴发迟发性脑梗塞二次卒中。大约两个人- 3/3的破裂动脉瘤患者将表现为中到重度 血管造影术后一周或以上血管痉挛程度 所以在最初的出血之后。这些患者中约有一半会 出现延迟性脑缺血的临床症状。由此产生的死亡率 这一现象近年来稳步下降，普遍存在 避免脱水和抗纤溶药物。此外, 钙拮抗剂、高血压和高容量血症可能对 然而，目前约有15%的患者仍将死亡 或者他因血管痉挛而严重受损。脑缺血的证据 在动脉瘤的致死病例中，约有30%出现梗塞。 如果在最初的几天内存活下来，就会破裂。 我们的长远目标是： (一)蛛网膜下腔出血后血管痉挛的预防 (2)已建立的血管痉挛的成功治疗。 具体目标是： 1)确定引起氧合血红蛋白的一个或多个成分 血管痉挛。(2)测定血管紧张素转换酶拮抗剂的疗效。 蛛网膜下腔出血后血管痉挛的治疗。(3)比较 组织型纤溶酶原激活剂与尿激活剂联合应用的疗效观察 治疗蛛网膜下腔凝块和预防血管痉挛。(四)调查研究 钙稳态在血管痉挛细胞机制中的作用 监测钙依赖的K+通道。(5)钙的表征 在脑血管平滑肌细胞中的通道并确定它们是如何 会受到血液成分的影响。(6)研究补血的作用。 脑血管平滑肌细胞钾通道的组成成分。 (7)检测血液成分对大脑皮层离子通道的作用 内皮细胞。