CO POISIONING IN THE CONTEXT OF A REPERFUSION INJURY

本研究项目的目的是阐明 一氧化碳介导的脑脂质过氧化， 在一氧化碳中毒的大鼠模型中发现。 CO是导致 在美国，12%或更多的人死于中毒， 幸存者在急性脑梗死后出现延迟性神经功能恶化， 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 被描述为“缺血-再灌注”现象。 我们建议 更详细地研究脂质过氧化的时间过程， CO暴露后的天数，并与脂质过氧化反应相关 使用（14 C）2-脱氧葡萄糖成像进行功能改变， 磷NMR光谱。 脑脂质的机制 将使用各种技术研究过氧化作用。 我们将 通过评估黄嘌呤氧化酶的作用， 酶抑制，使用钨，对脂质的发展 一氧化碳中毒后的过氧化反应 黄质的时程 CO中毒后脱氢酶向黄嘌呤氧化酶的转化 也将被衡量。 我们将评估 通过在CO氧化后的不同时间测量脑H2 O2， 暴露;并通过确定输注的影响， 二甲基硫脲，H2 O2清除剂，去铁胺，铁 螯合剂和脂质体包封的抗氧化酶（超氧化物 歧化酶和/或过氧化氢酶）对CO介导的脂质过氧化作用的影响。 我们 我还建议更详细地研究我们的观察， 高压氧（HBO）对CO介导脂质拮抗作用 过氧化作用 这些研究将涉及进一步的体内 实验中，CO后不同时间给予HBO 中毒;以及使用黄嘌呤氧化酶的进一步体外实验 产生自由基以评估O2浓度和PH的影响 对亚油酸过氧化的影响

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.