PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASM

慢性脑血管痉挛的病理生理学

• 批准号: 2265745
• 负责人: BRYCE K WEIR
• 金额: $ 32.63万
• 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/2265745
• 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（研究者摘要）：大约30，000名北美人 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，几乎唯一的沉积物是 基底动脉外膜侧有大量血凝块 这是一种慢性病，是慢性病的一种表现。 持续的动脉收缩称为血管痉挛。 血管痉挛可能是如此 严重的是，血管实际上可能被闭塞，远端缺血可 导致第二次卒中时伴随延迟性梗死。大约两个- 三分之一的破裂动脉瘤患者将显示中度至重度 血管造影性血管痉挛程度，如果接受血管造影一周，或 在最初的出血之后这些患者中约有一半将 出现迟发性缺血的临床体征。这类疾病的死亡率 近年来，随着广泛的 避免脱水和抗纤维蛋白溶解剂。此外，本发明还提供了一种方法， 钙拮抗剂、高血压和高血容量症可能会产生 然而，目前仍有约15%的患者会死亡， 要么就是血管痉挛严重受损脑缺血证据 在约30%的致死性脑梗死病例中， 如果它们能存活几天就会破裂 我们的长期目标是： (I)蛛网膜下腔出血后血管痉挛的预防 (2)成功治疗血管痉挛。 具体目标是： 1）确定氧合血红蛋白的哪种或哪些成分导致 血管痉挛 (2)为了确定内皮素拮抗剂在 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酶联合溶栓疗效观察 和预防血管痉挛。(4)探讨 钙稳态在血管痉挛细胞机制中的作用 监测Ca？+依赖性K+通道(5)为了表征钙 脑血管平滑肌细胞中的通道，并确定它们如何 都受到血液成分的影响(6)为了研究血液的作用 脑血管平滑肌细胞钾通道的活性成分。 (7)检测血液成分对脑离子通道的作用 内皮细胞