ALCOHOL-OXYGEN TENSION INTERACTIONS IN LIVER

酒精性肝损伤领域的一个主要问题与 缺氧在损害组织生存能力中的作用。 我们实验室以前的研究表明，来自 酒精喂养的动物在吸氧时不能保持充足的能量状态 有缺陷。在目前的研究中，我们将确定慢性乙醇是否 食用会使完整的肝脏更容易受到缺氧性损伤。一个 解决这个问题的有效方法是监测肝脏的水平 改变氧含量时能量代谢产物的31P-核磁共振波谱 进入隔离肝脏的灌流液的张力。实验是 建议系统研究低氧、急性剂量的影响 乙醇，以及两者的组合，对灌流的能量状态 来自乙醇喂养和对照动物的肝脏。氧气的利用 由肝脏在所有条件下施加的将由 利用显微技术连续测量进、出水氧分压 氧气电极。 拟议的研究是独一无二的，因为它将允许持续监测 肝脏高能磷代谢产物与氧利用 在养分可利用性和氧分压为 严格控制。这将使我们能够建立关系 氧分压、乙醇代谢、氧利用与能量 在长期食用乙醇的动物的肝脏中存在这种状态。本研究 与人类状况有关，在那里它已经被证明 酒精性肝坏死可见肝组织萎缩 静脉血氧分压。

A major question in the area of ethanol-induced liver damage relates to the role of oxygen deprivation in compromising the viability of the tissue. Previous studies from our laboratory suggest that hepatocytes from ethanol-fed animals cannot maintain an adequate energy state when oxygen deficient. In the present study we will determine whether chronic ethanol consumption makes the intact liver more susceptible to hypoxic damage. A powerful approach to this problem is to monitor the levels of hepatic energy metabolites using 31P-NMR spectroscopy while varying the oxygen tension of the perfusate entering an isolated liver. Experiments are proposed to systematically investigate the effects of hypoxia, acute doses of ethanol, and combinations of the two, on the energy state of perfused livers from both ethanol-fed and control animals. The utilization of oxygen by the liver under all the conditions imposed will be determined by continuous measurements of influent and effluent oxygen tension using micro oxygen electrodes. The study proposed is unique in that it will allow continuous monitoring of high energy phosphorus metabolites and oxygen utilization in the liver under conditions ere nutrient availability and oxygen tension are stringently controlled. This will allow us to establish the relationships between oxygen tension, ethanol metabolism, oxygen utilization and energy state in livers of animals that are chronic ethanol consumers. This study is relevant to the human condition where it has been demonstrated in alcoholics with hepatic necrosis that there can be reductions in hepatic venous oxygen tension.