ENDOTHELIAL INJURY IN POSTNATAL INTESTINE

描述：调查人员提议研究 血管内皮细胞损伤在肠血流动力学中的作用 坏死性小肠结肠炎。他们提出了与临床相关的 肠道缺血在肠道的局部区域发展，并发生 继发性血管内皮损伤 肠道循环。具体地说，他们提交了内皮细胞 细胞损伤是NEC早期发病的重要部分；这 损伤抑制内皮源性松弛因子的产生 (EDRF)，损害区域血流灌注，最终损害 实质生存能力。为了检验这一假设，建议的 实验设计：(1)确定血管内皮细胞损伤 减少出生后肠系膜动脉产生EDRF的年龄- 依赖方式；(2)检查内皮细胞损伤是否改变 新生儿肠系膜动脉内压-流量关系的研究 年龄依赖的方式；(3)确定结构性损伤是否 内皮细胞以年龄相关的方式出现；以及(4)检查 如果内皮细胞损伤改变了肠道的反应 对外源性收缩和扩张刺激的血液循环- 依附时尚。血管内皮细胞损伤将被诱导 缺血/再灌流的应用，就此方法而言 重复性好，价格低廉，具有临床应用价值。研究将会是 在1日龄、3日龄和35日龄的猪身上进行，这种物种已经证明 成为发育生理学研究的优秀模式。 血管内皮细胞损伤对EDRF产生的影响 将包括体外技术，其中预收缩的松弛 动脉环和cGMP的产生可作为EDRF的标志物 制作。其他研究将探索内皮细胞的作用 活体对肠道血流动力学的损伤。调查人员预计 这项工作的结果可能与内皮损伤有关， 对肠道血管功能有显著的、年龄相关的影响。如果是这样，他们 提出这种伤害可能是许多不同“触发因素”共同之处 导致NEC的事件。

DESCRIPTION: The investigators propose to study the effects of endothelial cell injury on gut hemodynamics in the pathogenesis of necrotizing enterocolitis (NEC). They propose that clinically relevant gut ischemia develops within localized areas of the gut and occurs secondary to antecedent damage to the vascular endothelium which lines the intestinal circulation. Specifically, they submit that endothelial cell damage is an essential part of the early pathogenesis of NEC; this injury attenuates production of endothelium-derived relaxing factor (EDRF), impairs regional perfusion and eventually compromises parenchymal viability. To test this hypothesis, the proposed experiments are designed: (1) to determine if endothelial cell injury attenuates EDRF production by postnatal mesenteric arteries in an age- dependent fashion; (2) to examine if endothelial cell injury alters the pressure-flow relationship within postnatal mesenteric arteries in an age- dependent fashion; (3) to determine if structural injury to endothelial cells occurs in an age-dependent fashion; and (4) to examine if endothelial cell injury alters the response of the intestinal circulation to exogenous constrictor and dilator stimuli in an age- dependent fashion. Endothelial cell injury will be induced by application of ischemia/reperfusion, insofar as this method is reproducible, inexpensive and clinically relevant. Studies will be conducted in 1-, 3- and 35-day old swine, a species which has proven to be an excellent model for the study of developmental physiology. Assessment of the effects of endothelial cell injury on EDRF production will include in vitro techniques, wherein relaxation of precontracted artery rings and production of cGMP are used as markers of EDRF production. Other studies will explore the effects of endothelial cell injury on gut hemodynamics in vivo. The investigators expect that results of this work may implicate endothelial damage in causing significant, age-dependent effects on gut vascular function. If so, they propose that such injury may be common to a number of different "trigger events" leading to NEC.