FEEDING, ISCHEMIA, AND OXYGENATION IN DEVELOPING INTESTINE

肠道发育过程中的进食、缺血和氧合

• 批准号: 3733198
• 负责人: KAREN D CRISSINGER
• 金额: --
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3733198
• 关键词: animal age group; baby food; blood flow measurement; breast feeding; chromium; colitis; developmental nutrition; dietary control; disease /disorder model; ethylenediaminetetraacetate; gastrointestinal circulation; gastrointestinal nutrient absorption; gastrointestinal surgery; hemodynamics; histology; hypoxia neonatorum; ileum; intestinal villi; intestines; ischemia; jejunum; light microscopy; membrane permeability; milk; nutrition related tag; oxygen consumption; oxygen microelectrode; oxygen tension; oxygen transport; radionuclides; radiotracer; reperfusion; swine; tube feeding

The pathogenesis of necrotizing enterocolitis remains unknown but infectious agents, enteral alimentation, and mesenteric ischemia have often been invoked as primary initiators of the disease. Despite the prevailing opinion that feeding does play a role in the pathogenesis of enterocolitis, little is known about 1) postprandial responses of blood flow and oxygenation in the developing intestine, 2) the relationships among hemodynamics, oxygenation, and mucosal injury during ischemia and reperfusion in the presence of luminal nutrients, and 3) the contribution of individual nutrient components to intestinal injury during ischemia and reperfusion. Therefore, the overall objective of this proposal is to systemically characterize the changes in intestinal blood flow, oxygenation, and mucosal injury during feeding and ischemia in developing piglet intestine. The proposed studies will address the following specific questions: 1) What are the hemodynamic and oxygenation responses during feeding in developing intestine? Do these responses change with age and with nutrient composition of the test meal? Are the responses different for mother's milk compared to formula? 2) What changes occur in mucosal pO2 and mucosal blood flow during perfusion with luminal nutrients in developing intestine? Is there a significantly greater decrease in villous pO2 during feeding in newborn as compared to older age groups or as a function of luminal nutrient composition? 3) What are the relationships among oxygen consumption, tissue pO2, blood flow, and mucosal permeability during ischemia and reperfusion in the presence of luminal nutrients in developing intestine? Is the newborn intestine capable of regulating its blood flow as tissue pO2 decreases? Can the magnitude of mucosal injury induced by ischemia and reperfusion be correlated with villous pO2? If so, is the villous pO2 at which mucosal injury is detected higher in newborn intestine compared to older age groups? An isolated, autoperfused loop of ileum in piglets of ages 1 day, 3 days, 2 weeks, and 1 month will be utilized to measure total and fractionated blood flow, arteriovenous oxygen difference, venous pressure, and capillary pressure. Oxygen uptake, and total, pre-capillary, and post-capillary resistances will be calculated from the measured variables. Villous pO2 will be measured with an oxygen micro-electrode and mucosal blood flow by hydrogen gas clearance. Blood-to-lumen clearance of 51 chromium EDTA will be used to measure changes in mucosal permeability. Histologic damage will be assessed with light microscopy. The results of these studies should significantly extend current knowledge about the responses of the developing intestine to feeding and hemodynamic stress and may also provide useful information regarding the interactions of enteral feeding, blood flow, and necrotizing enterocolitis.

坏死性小肠结肠炎的发病机理仍然未知，但 传染性剂，肠饮食和肠系膜缺血经常有 被称为该疾病的主要发起者。 尽管有盛行 认为喂养确实在小肠结肠炎的发病机理中起作用， 关于1）血流的餐后反应知之甚少 发育中的肠中充氧，2） 缺血期间的血液动力学，氧合和粘膜损伤 在腔内营养的存在下再灌注，3）贡献 缺血期间肠道损伤的个体营养成分 再灌注。 因此，该提议的总体目标是 从系统地表征肠血流的变化， 进食期间的氧合和粘膜损伤 小猪肠。 拟议的研究将解决以下特定问题：1） 进食过程中的血液动力和氧合反应是什么 发展肠？ 这些反应会随着年龄的增长而随着营养而变化吗 测试餐的组成？ 母亲的回应有所不同吗 牛奶与配方奶相比？ 2）粘膜PO2和粘膜中发生了什么变化 发育中的肠道营养素灌注过程中的血液流动？ 进食期间绒毛PO2的减少明显更大 新生儿与老年人组相比或腔的函数 营养成分？ 3）氧之间的关系是什么 消耗，组织PO2，血流和粘膜渗透性 在发育中腔内营养的存在下，缺血和再灌注 肠？ 是能够调节血液流动的新生肠 随着组织PO2的减少？ 粘膜损伤的幅度可以 缺血和再灌注与绒毛PO2相关吗？ 如果是这样，就是 在新生儿肠中发现粘膜损伤更高的绒毛PO2 与老年人组相比？ 1天，3天，2岁的小猪中的孤立的，自动灌注的回肠环 几周和1个月将用于测量总血液和分数 流动，动氧差，静脉压力和毛细管 压力。 氧气吸收，总含量，毛细血管前和毛细血管后 电阻将根据测量变量计算。 绒毛PO2 将用氧微电极和粘膜血流测量 氢气清除。 51铬EDTA的血液至肺清除将 用于测量粘膜渗透性的变化。 组织学损害将 用光学显微镜评估。 这些研究的结果应显着扩展当前知识 关于发育中的肠对喂养和血液动力学的反应 压力，还可能提供有关相互作用的有用信息 肠内喂养，血流和坏死性小肠结肠炎。