MECHANISM AND THERAPY OF CEREBROVASCULAR SPASM

脑血管痉挛（CVS）是一种危及生命的后遗症， 患有蛛网膜下腔出血（SAH）。 CVS是一种延迟现象 包括脑动脉严重狭窄， 脑缺血或梗塞的风险。 尽管深入研究 尽管努力，CVS的原因仍然未知，没有有效的治疗方法， 确立了习 本研究的目的是测试以下内容 假设：IA。CVS是由血红蛋白的血管收缩作用引起的 (Hb)以及从红细胞释放的额外溶血产物; 1B.这些 血液中的试剂或其它物质也产生CVS的第二阶段， 以显著的病理变化为特征，包括 动脉壁CVS，在其深刻的初始阶段， 血管收缩，可以使用校准泄漏，流动导向逆转 将药物直接输送到管腔内的球囊导管 涉及的血管;和IIB。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的作用与 溶血产物对猫完整基底动脉直径的影响， 恒河猴 在脑桥前形成凝块的血红蛋白量 还将测量水箱。 关于假设B，我们将 确定各种血液成分对维持的血管的影响 在灌注室中持续长达9天的时间。 我们将量化 在整个灌注期间，这些血管的顺应性;然后， 通过电子显微镜和功能检查评估形态学变化 收缩室测量的变化。 我们对球囊导管的使用受到以下需求的刺激： 将有效的治疗剂递送到受限的血管区域中 以及需要开发方法来扩张已经成为 对血管扩张物质有抵抗力。 使用恒河猴，导管将 将其插入股动脉，并将其尖端放置在远端 椎动脉或近端基底动脉。 在第一组实验中， 脑池内注射 5-羟色胺;血管扩张剂腔内给药的作用 将通过血管造影术测定物质。 的第二集合中 实验中，将CVS通过蛛网膜下腔注射血液诱导;这些 将持续观察动物的CVS体征，此时 将研究血管扩张剂和血管成形术的作用。

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.