MECHANISM AND THERAPY OF CEREBROVASCULAR SPASM

脑血管痉挛(CVS)是威胁生命的后遗症 他们患有蛛网膜下腔出血(SAH)。严格意义上的 CVS包括严重的、持续的管腔狭窄 脑动脉，通常在5至10天后发病 萨哈。形态研究显示主要的退行性变 影响动脉壁各层的变化。因为我们的 初步研究表明，胆红素起主要作用 在简历开发中的作用，我们建议研究 以下假设：1.血管收缩和病理 胆红素对脑动脉的影响有剂量、时间和pH效应。 依附的。这些影响可以通过以下方式来减少 白蛋白。II.血管收缩和病理效应 来自10天孵化血液的血清遵循相同的模式 与胆红素一样，具有剂量、时间和pH依赖性。这些 白蛋白的存在也会降低这种影响。三. 胆红素和血清10日起的血管收缩作用 在平滑肌细胞上孵化的血液主要是由于 诱导钙离子内流增加。血管收缩可以是 被低钙介质减少，但内流不能减少 钙通道阻滞剂。四、血红素的分解代谢 在凝结的血液中会导致IXα胆红素的形成， 而不是形成大致相等的百分比 IX阿尔法、IX BATA、IX伽马和IX增量异构体。 假说V。血管的狭窄和病理改变。 蛛网膜下腔出血后的基底动脉可通过交付 通过动脉导管注射白蛋白。我们会调查的 通过测量猫的超微结构变化提出假设I和II 胆红素和胆红素在体应用对基底动脉的影响 从培养的血液中提取的血清。假设III将由以下人员检验 收缩腔法测量介质中的收缩力 同时具有生理和低钙水平，并由45Ca2+ 猫基底动脉浸浴节段摄取的研究 胆红素和来自孵化血液的血清中。假设四将是 经高效液相色谱仪检测胆红素异构体的形成 蛛网膜下腔血和孵化血中。假设V将是 通过量化血管内注射后的血管造影变化进行研究 动脉注射白蛋白给以前的动物 到蛛网膜下腔出血。

Cerebral vasospasm (CVS) is a life-threatening sequela for those who suffer subarachnoid hemorrhage (SAH). In its strict sense CVS consists of severe, sustained narrowing of the lumen of cerebral arteries and usually has its onset five to ten days after SAH. Morphological studies have shown major degenerative changes affecting all layers of the arterial wall. Because our preliminary studies have suggested that bilirubin plays a principal role in the development of CVs, we propose to investigate the following hypotheses: I. The vasoconstrictive and pathological effects of bilirubin on cerebral arteries are dose-, time-, and ph- dependent. These effects can be decreased by the presence of albumin. II. The vasoconstrictive and pathological effects of serum from 10 day incubated blood follow the same patterns of dose-, time-, and ph-dependence as those of bilirubin. These effects can also be decreased by the presence of albumin. III. The vasoconstrictive effect of bilirubin and of serum from 10 day incubated blood on smooth muscle cells is principally due to the induction of increased Ca2+ influx. The vasoconstriction can be decreased by low Ca2+ media, but the influx cannot be decreased by calcium channel blocking agents. IV. The catabolism of heme in clotted blood leads to the formation of IX alpha bilirubin, rather than to the formation of approximately equal percentages of the IX alpha, IX bata, IX gamma and IX delta isomers. Hypothesis V. The constrictive and pathological changes in basilar arteries following SAH can be reduced by delivery of albumin via an intra-arterial catheter. We will investigate Hypotheses I and II by measuring ultrastructural changes of cat basilar artery following in vivo application of bilirubin and of serum from incubated blood. Hypothesis III will be examined by contraction chamber measurement of contractile forces in media with both physiological and low levels of Ca2+ and by 45Ca2+ uptake studies on segments of cat basilar artery bathed in bilirubin and in serum from incubated blood. Hypothesis IV will be tested by HPLC analyst of bilirubin isomers formed in subarachnoid blood and in incubated blood. Hypothesis V will be investigated by quantitating angiographic changes following intra- arterial administration of albumin to animals previously subjected to subarachnoid hemorrhage.