MECHANISM AND THERAPY OF CEREBROVASCULAR SPASM

脑血管痉挛(CVS)是威胁生命的后遗症 患有蛛网膜下腔出血(SAH)。CVS是一种延迟现象 包括严重的脑动脉狭窄，导致高 有脑缺血或脑梗塞的风险。尽管进行了密集的研究 经过努力，CVS的原因仍不清楚，目前还没有有效的治疗方法 已经建立了。这项研究的目标是测试以下内容 假设：IA。血管痉挛是由血红蛋白的血管收缩作用引起的 (Hb)和从红细胞释放的额外溶血物；IB。这些 血液中的试剂或其他物质也会产生第二阶段的CVS， 以明显的病理变化为特征的，包括增生 动脉壁；IIA。CVS，在其深刻的初始阶段 血管收缩，可使用校准泄漏、流动导向逆转 气囊导管将药物直接输送到管腔内 所涉船只的数目；以及国际投资参考协会。CVS，在血管病变的后期， 可以通过使用动脉内、血管成形术导管来缓解。 我们将通过比较HB和HB的影响来研究假设IA 溶血素对猫完整基底动脉内径的影响 恒河猴。桥前区血栓中形成的Hb的量 蓄水池也将被测量。关于假设IB，我们将 确定各种血液成分对维持的血管的影响 在灌注室中持续时间长达9天。我们将量化 这些血管在整个灌注期内的顺应性；届时我们将 通过电子显微镜和功能性检查评估形态变化 通过收缩腔测量的变化。 我们对气囊导管的使用是因为需要 将有效的治疗剂输送到受限的血管区域 以及需要开发方法来扩展已经成为 对血管扩张物质有抵抗性。利用恒河猴，导尿管将 将其插入股动脉，并将其末端放置在远端 椎动脉或近端基底动脉。在第一组实验中， 脑池内注射可引起血管狭窄 5-羟色胺；血管扩张血管腔内给药的作用 物质将通过血管造影术确定。在第二组 实验中，蛛网膜下腔注射血液会诱发脑血管痉挛；这些 动物将被持续观察是否有CVS的迹象，届时 将研究血管扩张剂和血管成形术的效果。

Cerebrovascular spasm (CVS) is a life-threatening sequela for those who suffer subarachnoid hemorrhage (SAH). CVS occurs as a delayed phenomenon and consists of severe narrowing of cerebral arteries, resulting in high risk of cerebral ischemia or infarction. Despite intensive research effort, the cause of CVS remains unknown, and no effective treatment has been established. The objectives of this study are to test the following hypotheses: IA. CVS is induced by vasoconstrictive action of hemoglobin (Hb) and of additional hemolysates released from red blood cells; IB. these agents or other substances in blood also produce a second stage of CVS, characterized by marked pathological changes, including hyperplasia, of the arterial wall; IIA. CVS, during its initial stage of profound vasoconstriction, can be reversed using calibrated-leak, flow-directed balloon catheters to deliver pharmacological agents directly into the lumen of involved vessels; and IIB. CVS, during the later stage of vasculopathy, can be relieved through the use of intra-arterial, angioplasty catheters. We will investigate Hypothesis IA by comparing the effect of Hb with that of hemolysate upon the diameter of the intact basilar artery in cats and rhesus monkeys. The amounts of Hb which develop in clots in the prepontine cistern will also be measured. With regard to Hypothesis IB, we will determine the effects of various blood components upon vessels maintained in perfusion chambers for periods up to 9 days. We will quantitate the compliance of these vessels throughout the perfusion period; we will then assess both morphological changes by electron microscopy and functional changes by contraction chamber measurements. Our utilization of balloon-tipped catheters is stimulated by the need for delivering potent therapeutic agents into restricted vascular territories and by the need for developing methods to expand vessels which have become resistant to vasodilating substances. Using rhesus monkeys, catheters will be inserted into a femoral artery and their tips placed within the distal vertebral or proximal basilar arteries. In the first set of experiments, vascular narrowing will be induced by intra-cisternal injection of serotonin; the effects of intraluminal administration of vasodilating substances will be determined by angiography. In the second set of experiments, CVS will be induced by subarachnoid injection of blood; these animals will be continuously observed for signs of CVS, at which time the effects of vasodilating agents and of angioplasty will be studied.