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）的患者。 从严格意义上说 CVS包括严重的，持续的管腔狭窄， 脑动脉，通常发病后5至10天 SAH。 形态学研究表明， 影响动脉壁各层的变化。 因为我们的 初步研究表明，胆红素在 在简历开发中的作用，我们建议调查 以下假设：I. 血管收缩和病理性 胆红素对脑动脉的影响有剂量效应、时间效应和ph效应。 依赖。 这些影响可以通过以下物质的存在来降低： 白蛋白。 二. 血管收缩和病理作用 来自孵育10天的血液的血清遵循相同的模式 剂量依赖性、时间依赖性和pH依赖性。 这些 白蛋白的存在也会降低这种作用。 三. 胆红素和10天后血清的血管收缩作用 在平滑肌细胞上孵育的血液主要是由于 诱导增加的Ca 2+内流。 血管收缩可以是 低Ca ~（2+）培养基可降低细胞内流，但不能降低细胞内流 钙通道阻滞剂的作用 四. 血红素的催化作用 导致IX α胆红素的形成， 而不是形成大致相等的百分比 IX α、IX β、IX γ和IX δ异构体。 假设五： 蛛网膜下腔出血后的基底动脉可以通过输送 通过动脉内导管输注白蛋白。 我们将调查 通过测量猫的超微结构变化来验证假设I和假设II 在体内应用胆红素和 培养血液中的血清。 假设三将由 收缩室测量介质中的收缩力 生理和低水平的Ca 2+和45 Ca 2 + 猫基底动脉血管段的摄取研究 胆红素和来自孵育血液的血清中的胆红素。 假设四： 由HPLC分析员检测形成的胆红素异构体 蛛网膜下腔血液和孵育血液中。 假设V是 通过定量血管造影变化进行研究， 对先前接受过白蛋白给药的动物进行动脉给药 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.