GUT ISCHEMIA: OXYGEN DELIVERY AND SUPEROXIDE RADICALS

肠道缺血：氧气输送和超氧自由基

• 批准号: 3232673
• 负责人: RONALD W MILLARD
• 金额: $ 12.24万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-16 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232673
• 关键词: adenosine triphosphate; beta glucuronidase; citrate synthase; electron microscopy; free radicals; gastrointestinal circulation; glutamates; hypoxanthines; hypoxia; lactates; malonaldehyde; oxoacid lyase; oxygen transport; phosphates; pyruvates; superoxides; urate; xanthines

The mortality rate from intestinal ischemia is near 100% and accounts for 3% of the deaths in this country. Considerable attention has been directed to improvement of intestinal blood flow with vasodilator drugs. However, the contribution of low flow, per se, as distinct from hypoxia to mucosal injury has not been clearly demonstrated. Accordingly, we propose to investigate the roles of oxygen delivery and blood flow in the genesis of mucosal injury in isolated segments of canine ileum. Four series of experiments will be conducted. Perfusion with venous blood with high and low oxygen content will be contrasted with arterial blood perfusion at normal flow levels. Low flow perfusion with arterial blood will be combined with luminal perfusion with normal physiological saline, with a glucose load to stimulate metabolism and with a fluorocarbon emulsion to enhance oxygen delivery. Low flow perfusion effects of arterial blood containing either fluorocarbon emulsion or inositol hexaphosphate treated erythrocytes to enhance vascular oxygen delivery will be determined. The effects of added intrarterial vasodilators will be determined during low pressure and low flow perfusion. Vascular resistance will be used as an index of the local circulatory responses. Blood flow distribution between mucosal/submucosal and muscularis regions of each intestinal segment will be determined by radionuclide microspheres. Serial tissue samples will be analyzed for ATP, xanthine, hypoxanthine, uric acid, inorganic phosphate, lactate/pyruvate ratio, glutamate-oxaloacetate transaminase, citrate synthase, Beta-glucuronidase and malondialdehyde to estimate the involvement of cytotoxic oxygen radicals in the morphologic alterations associated with ischemia. Light, scanning, and transmission electron microscopy will document morphologic changes and scanning, and transmission electron microscopy will document morphologic changes and scanning, and transmission electron microscopy will document morphologic changes and the time course of the cellular events. The results of these studies will provide new insights of the causative factors which precipitate the fatal consequences of circulatory insufficiency in the intestine.

肠缺血的死亡率接近100%， 占这个国家死亡人数的3%。 相当多的注意力已经集中在 用血管扩张药物改善肠血流量。 然而，在这方面， 与缺氧不同，低流量本身对粘膜损伤的贡献 伤害没有得到明确证明。 因此，我们建议 研究氧气输送和血流在肺动脉高压发生中的作用， 犬离体回肠段粘膜损伤。 四大系列 将进行实验。 静脉血灌注， 低氧含量将与动脉血液灌注形成对比， 正常流量水平。 动脉血低流量灌注将是 结合生理盐水管腔灌注， 葡萄糖负荷以刺激新陈代谢，并使用氟碳乳剂， 增强氧气输送。 动脉血的低流量灌注效应 含有碳氟乳液或经肌醇六磷酸处理的 将确定红细胞增强血管氧输送。 的 将在低血糖期间确定添加动脉内血管扩张剂的效果。 压力和低流量灌注。 血管阻力将用作 局部循环反应指数。 血流分布 每个肠段的粘膜/粘膜下和肌层区域将 用放射性核素微球测定。 连续组织样本将 分析ATP、黄嘌呤、次黄嘌呤、尿酸、无机磷酸盐， 乳酸/丙酮酸比值，谷草转氨酶，柠檬酸 合成酶，β-葡萄糖醛酸酶和丙二醛，以估计 细胞毒性氧自由基参与形态学改变 与局部缺血有关。 光、扫描和透射电子 显微镜将记录形态变化，扫描和透射 电子显微镜将记录形态学变化和扫描， 透射电子显微镜将记录形态学变化， 细胞活动的时间进程。 这些研究的结果将 提供了新的见解的致病因素，沉淀的致命 肠循环功能不全的后果。