FEEDING, ISCHEMIA, AND OXYGENATION IN DEVELOPING INTESTINE

坏死性小肠结肠炎的发病机制尚不清楚， 感染因子、肠内营养和肠系膜缺血常常 被认为是该疾病的主要始作俑者。 尽管目前 认为进食在小肠结肠炎的发病机制中确实起作用， 关于1）血流量的餐后反应和 氧合在发育中的肠道，2）之间的关系 血液动力学、氧合和粘膜损伤， 再灌注腔营养物质的存在下，和3）的贡献 个别营养成分的肠损伤缺血和 再灌注 因此，本建议的总体目标是 系统地表征肠血流的变化， 氧合和粘膜损伤在喂养和缺血在发展 猪肠 拟议的研究将针对以下具体问题： 喂养期间的血流动力学和氧合反应如何？ 发育中的肠道 这些反应是否随年龄和营养而变化 测试餐的组成？ 妈妈的反应不同吗 牛奶与配方奶粉相比？ 2)粘膜pO 2和粘膜pO 2 在肠腔营养灌注过程中的血流？ 在喂食过程中， 新生儿与老年组相比或作为管腔功能 营养成分？ 3)氧气和氧气之间的关系是什么 消耗，组织pO 2，血流量和粘膜渗透性， 缺血和再灌注的管腔营养物质的存在下，在发展中国家 肠子？ 新生的肠道能够调节血液流动吗 随着组织pO 2的降低？ 是否可以通过改变胃黏膜的损伤程度 缺血再灌注与绒毛组织pO 2有关？ 如果是这样， 在新生儿肠道中检测到粘膜损伤的绒毛pO 2较高 与老年人相比，？ 本实验采用离体回肠袢，对1日龄、3日龄、2日龄仔猪进行了自体灌流， 将使用1周和1个月测量全血和部分血液 血流、动静脉氧差、静脉压和毛细血管 压力 氧摄取量和总氧摄取量、毛细血管前氧摄取量和毛细血管后氧摄取量 电阻将根据测量的变量计算。 绒毛pO 2 将用氧微电极和粘膜血流量测量， 氢气清除。 51铬EDTA的血液-管腔清除率将 用于测量粘膜渗透性的变化。 组织损伤将 用光学显微镜进行评估。 这些研究的结果应该大大扩展了现有的知识 关于发育中的肠道对进食和血液动力学的反应 强调，也可以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的影响。

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.