HYPOXIA EFFECTS ON AMNIOTIC FLUID VOLUME

正常量的羊水必须存在，以便胎儿 正常生长发育 羊水过少（羊水过少 液体）发生在大约5%的人类妊娠中， 导致许多紧急剖腹产，子宫内胎儿死亡 由于脐带压迫，以及由于呼吸道感染 痛苦 尽管人们普遍认为胎儿缺氧会导致 羊水过少，缺氧对羊水量的影响， 没有被实验研究过。 间接证据表明，胎儿 缺氧实际上可能导致羊水过多（过多的羊水） 而不是羊水过少 拟议的研究将确定 缺氧对胎羊羊水量的影响及探讨 这些影响的机制。总体假设是胎儿 缺氧引起羊水过多和胎儿缺氧 胎盘功能不全导致羊水过少 具体目标 第一，胎儿缺氧会产生进行性胎儿贫血 （贫血性缺氧）。 假设会有一个阈值， 羊水量会大量增加， 依赖于胎儿血浆乳酸和精氨酸加压素升高 程度. 在具体目标2中，胎儿将通过以下方式缺氧： 减少母亲的吸入氧含量（缺氧性缺氧）。 假设羊水过多会发展， 其机制与贫血性缺氧时发生的机制相同。 具体目标 第三，胎儿会被反复的微球 脐循环栓塞 假设是， 胎儿缺氧和胎盘功能不全的结合会产生 羊水过少对于每一个具体目标，相关的 将通过监测胎儿尿的产生、胎儿发育和胎儿发育来研究其机制。 吞咽、肺液体分泌和羊水量 通过膜内途径吸收。 每项具体变化 这四种流动对于每种产生胎儿的方法都是假设的。 缺氧 我们认为羊水量的变化 从四个测量的流量中准确预测。总体而言，拟议 这些研究很重要，因为它们将极大地改善我们的 了解胎儿羊水量的调节， 常氧和缺氧条件下。这是临床相关的，因为 增加对调节羊水的机制的理解 量应导致更好的治疗，以维持正常的羊膜 在人类怀孕期间，这将有助于减少胎儿 以及新生儿发病率和死亡率。

Normal amounts of amniotic fluid must be present in order for the fetus to grow and develop normally. Oligohydramnios (too little amniotic fluid) occurs in approximately 5 percent of human pregnancies and is responsible for many emergency cesarean sections, in utero fetal deaths due to cord compression, and neonatal deaths due to respiratory distress. Although it is widely assumed that fetal hypoxia causes oligohydramnios, the effects of hypoxia on amniotic fluid volume have not been studied experimentally. Indirect evidence suggests that fetal hypoxia may actually cause polyhydramnios (too much amniotic fluid) rather than oligohydramnios. The proposed studies will determine the effects of hypoxia on amniotic fluid volume in fetal sheep and explore the mechanisms of these effects. The overall hypothesis is that fetal hypoxia produces polyhydramnios and that fetal hypoxia in combination with placental insufficiency causes oligohydramnios. In Specific Aim number 1, fetal hypoxia will be produced by progressive fetal anemia (anemic hypoxia). The hypothesis is that there will be a threshold at which a large increase in amniotic fluid volume occurs and this is dependent upon elevated fetal plasma lactate and arginine vasopressin levels. In Specific Aim number 2, the fetus will be made hypoxic by reducing the inspired oxygen content of the mother (hypoxic hypoxia). The hypothesis is that polyhydramnios will develop and the associated mechanisms are the same as occur during anemic hypoxia. In Specific Aim number 3, the fetus will be made hypoxic by repeated microsphere embolizations of the umbilical circulation. The hypothesis is that this combination of fetal hypoxia and placental insufficiency will produce oligohydramnios. For each of these Specific Aims, the associated mechanisms will be studied by monitoring fetal urine production, fetal swallowing, lung liquid secretion, and the volume of amniotic fluid absorbed via the intramembranous pathway. Specific changes in each of these four flows are hypothesized for each method of creating fetal hypoxia. We expect the changes in amniotic fluid volume to be accurately predicted from the four measured flows. Overall, the proposed studies are important because they will dramatically improve our understanding of amniotic fluid volume regulation in the fetus under normoxic and hypoxic conditions. This is relevant clinically because an increased understanding of the mechanisms which regulate amniotic fluid volume should lead to better therapies for maintaining normal amniotic fluid volumes during human pregnancy and this would help reduce fetal and neonatal morbidity and mortality.