HYPOXIA EFFECTS ON AMNIOTIC FLUID VOLUME

为了胎儿，必须有正常数量的羊水 正常生长正常生长和发育。羊水过少(羊水过少 体液)发生在大约5%的人类怀孕中，并且 负责许多紧急剖宫产，宫内胎儿死亡 由于脐带受压，以及新生儿因呼吸道死亡 苦恼。尽管人们普遍认为胎儿缺氧会导致 羊水过少，低氧对羊水量的影响 没有经过实验研究。间接证据表明，胎儿 缺氧实际上可能导致羊水过多(羊水过多) 而不是羊水过少。建议的研究将决定 低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 缺氧会导致羊水过多和胎儿缺氧 胎盘功能不全会导致羊水过少。以特定的目标 第一，进行性胎儿贫血会导致胎儿缺氧 (贫血、缺氧)。这个假设是，在 羊水量出现大幅增加，这就是 依赖于胎儿血浆乳酸和精氨酸加压素的升高 级别。在特定的目标2中，胎儿将通过以下方式造成缺氧 减少母亲吸入的氧气含量(缺氧性缺氧)。 假设羊水过多会发展成相关的 其机制与贫血时相同。以特定的目标 第三，重复使用微球会使胎儿缺氧。 脐循环的栓塞术。假设是这样的 胎儿缺氧和胎盘功能不全会产生 羊水过少。对于这些特定目标中的每一个，相关的 机制将通过监测胎儿尿液产生、胎儿 吞咽、肺液分泌和羊水量 通过膜内途径吸收。每一项的具体变化 对于每种创建胎儿的方法都假设了这四种流 缺氧。我们预计羊水量的变化将是 从四个测得的流量中准确预测。整体而言，建议的 研究很重要，因为它们将极大地改善我们的 胎儿期羊水量调节的认识 常氧和低氧条件。这在临床上是相关的，因为 加深对羊水调节机制的了解 容量应该会带来更好的维持正常羊水的治疗方法 人类怀孕期间的液体量，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.