CONTRAST MEDIA REDUCE CSF PRODUCTION MECHANISM/TOXICITY

造影剂不良反应的原因尚不清楚 可以理解，但可能涉及CM诱导的中枢神经系统的改变， 系统（CNS）。 血脑屏障（BBB）严格控制着 物质进入CNS。 脑脊液（CSF）的产生率为 这是从中枢神经系统中清除物质的关键因素。 这两个因素 从而维持和控制CNS的化学环境。 如果任何一 因子被破坏，可能出现中毒表现。 这两个因素都可能是 被CM改变 造影剂的毒性是普通造影剂的几百倍 在CNS中比在全身中更有效，并且能够破坏BBB。 实验 在来自该实验室的狗中显示，中等剂量的离子和 非离子静脉内CM显著降低CSF产生。 因此，我们认为， CM可能会改变CNS的环境，并导致 毒性 对CM影响CSF产生的机制进行了探讨 在拟议的工作中研究。 清醒和麻醉的实验动物 模型和体外制剂将用于确定： CM诱导的CSF产生增加的机制; CNS CM的这种作用导致的毒性;浓度的变化， 由CM引起的CNS中物质的保留和动力学;增强 通过额外降低CM诱导毒性的某些风险因素， CSF产生或通过使BBB易受CM的破坏性影响;以及 可以保护免受CM的这些影响。

The causes of the adverse responses to contrast media (CM) are not well understood but may involve CM-induced alterations of the central nervous system (CNS). The blood brain barrier (BBB) strictly controls access of substance to the CNS. The rate of cerebrospinal fluid (CSF) production is a key factor in eliminating substances from the CNS. These two factors thus maintain and control the chemical environment of the CNS. If either factor is disrupted, toxic manifestations could occur. Both factors can be altered by CM. Contrast media are up to several hundred times more toxic in the CNS than systemically, and are able to disrupt the BBB. Experiments in dogs from this laboratory show that moderate doses of both ionic and non-ionic intravenous CM substantially decrease CSF production. Therefore, CM might be expected to alter the environment of the CNS and result in toxicity. The mechanisms of CM effects on the production of CSF will be studied in the proposed work. Conscious and anesthetized laboratory animal models and in vitro preparations will be employed to determine: the mechanisms of CM-induced ecreased CSF production; the extent of CNS toxicity resulting from this action of CM; changes in the concentration, retention and kinetics of substances in the CNS caused by CM; enhancement by certain risk factors of CM-induced toxicity by additionally decreasing CSF production or by predisposing the BBB to damaging effects of CM; and if it is possible to protect from these effects of CM pharmacologically.