CO POISIONING IN THE CONTEXT OF A REPERFUSION INJURY

本研究的目的是阐明黄褐斑的发病机制。 一氧化碳介导的大脑脂质过氧化，我们有 在一氧化碳中毒的大鼠模型中被鉴定。CO是主要原因 在美国，有12%或更多的人死于中毒 幸存者在急性脑出血后神经功能延缓恶化 侮辱。这种延迟过程的机制尚不清楚，但它 被认为是氧化损伤。我们的假设是 我们模型中的脂质过氧化反应代表了流行的 被描述为“缺血-再灌流”现象。我们建议 更详细地研究脂质过氧化的时间进程 一氧化碳暴露后的天数，并与脂质过氧化相关 使用(14C)2-脱氧葡萄糖显像和 磷核磁共振光谱学。脑部脂肪的作用机制 过氧化作用将使用各种技术进行研究。我们会 通过评估黄嘌呤氧化酶的影响来评估黄嘌呤氧化酶的作用 酶抑制，使用钨，对脂肪的发育 一氧化碳中毒后的过氧化反应。黄嘌呤的时间进程 一氧化碳中毒后脱氢酶向黄嘌呤氧化酶的转化 也将被测量。我们将评估 一氧化碳后不同时间测定脑内H202氧化剂 以及还通过确定输注 二甲基硫脲，H202清除剂，去铁胺，铁 螯合剂和脂质体包裹的抗氧化酶(超氧化物 对CO介导的脂质过氧化的影响。我们 还建议更详细地研究我们的观察结果，包括 高压氧对CO介导的脂质的拮抗作用 过氧化。这些研究将涉及进一步的活体研究。 高压氧在CO术后不同时间给药的实验研究 使用黄嘌呤氧化物酶进行进一步的体外实验 生成自由基以评估02浓度和PH值的影响 关于亚油酸过氧化。

The aim of this research project is to elucidate the mechanism of carbon mon-oxide-mediated brain lipid peroxidation, which we have identified in a rat model of CO poisoning. CO is the leading cause of death by poisoning in the United States, and 12% or more of survivors suffer delay neurologic deterioration after the acute insult. The mechanism for this delayed process is unknown, but it is hypothesized to be an oxidative injury. Our hypothesis is that lipid peroxidation in our model represents what is popularly described as an "ischemia-reperfusion" phenomenon. We propose to study the time course for lipid peroxidation in greater detail over the days following CO exposure, and to correlate lipid peroxidation with functional changes using (14C) 2-deoxyglucose imaging and phosphorous NMR spectroscopy. The mechanism for brain lipid peroxidation will be studied using various techniques. We will evaluate the role of xanthine oxidase by assessing the impact of enzyme inhibition, using tungsten, on the development of lipid peroxidation after CO poisoning. The time course of xanthin dehydrogenase to xanthine oxidase conversion after CO poisoning will also be measured. We will evaluate the involvement of oxidants by measuring brain H202 at various times subsequent to CO exposure; and also by determining the impact of infusion of dimethylthiourea, an H202 scavenger, desferrioxamine, an iron chelator, and liposome-encapsulated antioxidant enzymes (superoxide dismutase and/or catalase) on CO-mediated lipid peroxidation. We also propose to study in greater detail our observation involving hyperbaric oxygen (HBO) antagonism of CO-mediated lipid peroxidation. These studies will involve further in vivo experiments, administration of HBO at different times after CO poisoning; and further in vitro experiments using xanthine oxidase generated radicals to assess the impact of 02 concentration and PH on linoleic acid peroxidation.