FEEDING, ISCHEMIA, AND OXYGENATION IN DEVELOPING INTESTINE

坏死性小肠结肠炎的发病机制仍不清楚，但 感染原、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。 尽管盛行 认为喂养确实在小肠结肠炎的发病机制中发挥作用， 对于 1) 餐后血流反应和 发育中肠道的氧合，2) 之间的关系 缺血期间的血流动力学、氧合和粘膜损伤 在管腔营养物存在的情况下再灌注，以及 3) 的贡献 缺血期间各个营养成分对肠道损伤的影响 再灌注。 因此，本提案的总体目标是 系统地表征肠道血流的变化， 喂养过程中的氧合和粘膜损伤以及发育过程中的缺血 仔猪肠。 拟议的研究将解决以下具体问题：1） 喂养期间的血流动力学和氧合反应是什么 发育中的肠道？ 这些反应会随着年龄和营养的变化而变化吗 测试餐的成分？ 母亲的反应是否不同 牛奶与配方奶粉相比？ 2）粘膜pO2和粘膜氧分压发生什么变化？ 发育中的肠道内灌注管腔营养物质时的血流量？ 喂养期间绒毛 pO2 是否有显着更大的下降？ 新生儿与较大年龄组相比或作为管腔的函数 营养成分？ 3）氧之间有什么关系 消耗量、组织 pO2、血流量和粘膜通透性 发育中存在管腔营养物的情况下的缺血和再灌注 肠？ 新生儿肠道能够调节血流吗 当组织 pO2 降低时？ 是否会引起粘膜损伤的程度 缺血和再灌注与绒毛 pO2 相关吗？ 如果是的话，是 绒毛 pO2 在新生儿肠道中检测到粘膜损伤较高 与年龄较大的群体相比？ 1 日龄、3 日龄、2 日龄仔猪的分离、自灌注回肠环 周和 1 个月将用于测量总血和分级血 流量、动静脉氧差、静脉压和毛细血管 压力。 摄氧量和总摄氧量、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。 绒毛氧分压 将通过氧气微电极和粘膜血流量进行测量 氢气清除。 51 铬 EDTA 的血液至管腔清除率 用于测量粘膜通透性的变化。 组织学损伤将 通过光学显微镜进行评估。 这些研究的结果应该会显着扩展当前的知识 关于发育中的肠道对进食和血流动力学的反应 压力，还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。

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.