FEEDING, ISCHEMIA, AND OXYGENATION IN DEVELOPING INTESTINE

坏死性小肠结肠炎的发病机制尚不清楚，但 感染性因素、肠内营养和肠系膜缺血 被作为疾病的主要发起者而被援引。尽管盛行 认为喂食在小肠结肠炎的发病机制中确实起到了作用， 鲜为人知的是1)餐后血液流动和 发育中的肠道中的氧合作用，2) 缺血时的血流动力学、氧合作用和粘膜损伤 腔内营养素存在时的再灌流，以及3)贡献 不同营养成分对肠缺血损伤的影响 再灌流。因此，这项建议的总体目标是 系统地描述肠道血流的变化， 摄食过程中的氧合作用、粘膜损伤和发育中的缺血 仔猪肠道。 拟议的研究将涉及以下具体问题：1) 喂食过程中的血流动力学和氧合反应是什么？ 肠子发育吗？这些反应是否随着年龄和营养的变化而变化？ 试餐的成分是什么？对于母亲的反应是否有所不同 牛奶和配方奶相比吗？2)粘膜的氧分压和粘膜发生了什么变化 在发育中的肠道，腔内营养素灌流时的血流？ 在喂养过程中，绒毛PO2的下降幅度是否显著 新生儿与年龄较大的群体相比，或作为卢米纳的函数 营养成分？3)氧气之间有什么关系？ 消耗、组织氧分压、血流量和粘膜通透性 发育中存在管腔营养素的缺血再灌流 肠子？新生儿的肠道能调节它的血液流动吗 当组织中的PO2下降时？大鼠胃粘膜损伤程度能不能 缺血再灌注与绒毛PO2？如果是这样，那么 新生儿肠道黏膜损伤程度较高的绒毛状PO2 与年长的年龄段相比？ 在1日龄、3日龄、2日龄仔猪身上形成一个孤立的、自灌流的回肠 周和1个月将被用来测量总血液和部分血液 血流量、动静脉血氧差、静脉压和毛细血管 压力。摄氧量、总摄氧量、毛细血管前和毛细血管后 电阻将根据测量的变量计算出来。绒毛状PO2 将用氧气微电极测量和粘膜血流量通过 氢气清除。51铬EDTA的血液到管腔清除将 用于测量粘膜通透性的变化。组织学损伤会 用光学显微镜进行评估。 这些研究的结果应该会大大扩展现有的知识 关于发育中的肠道对摄食和血流动力学的反应 并且还可以提供关于相互作用的有用信息 肠道喂养、血流和坏死性小肠结肠炎。

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.