PREVENTION AND TREATMENT OF HUMAN OLIGOHYDRAMNIOS

人类脑水肿的预防和治疗

基本信息

批准号：
6387892
负责人：
Michael Glenn Ross
金额：
$ 20.38万
依托单位：
LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-05-05 至 2003-04-30
项目状态：
已结题

项目摘要

Early in normal human pregnancy, maternal plasma osmolality decreases and plasma volume increases. A failure to achieve adequate plasma volume expansion is associated with adverse pregnancy outcomes, including reduced amniotic fluid (AF) volume (oligohydramnios). Oligohydramnios occurs in 8 to 38 percent of all pregnancies and is associated with significant perinatal morbidity and mortality. Our recent experiments confirm the central role of placental osmotic gradients in the modulation of fetal fluid acquisition. We have established that maternal DDAVP and oral water administration induces maternal and fetal physiologic responses which increase AF volume. Specifically, ovine maternal and fetal plasma hypo-osmolality expands maternal plasma volume and increases fetal fluid acquisition, fetal urine production and thus AF volume. We have developed a conceptual model based on existing literature and our studies, temporally linking the resetting of maternal plasma osmolality and arginine vasopressin (AVP) secretory thresholds, maternal plasma volume expansion and AF volume. Our preliminary studies indicate that a fasting, morning plasma osmolality/sodium may be utilized as a simplified "index" of the maternal plasma osmolality threshold for AVP secretion, permitting repeated determinations of threshold setpoints throughout gestation. These hypotheses will be addressed in a stepwise series of human investigations. Firstly, we will establish the utility of a simplified index of the plasma osmolality/sodium setpoint for AVP secretion in nonpregnant patients and will confirm this index in a cross- sectional study of pregnant patients throughout gestation. Secondly, gestational changes and population distributions of plasma osmolality setpoint will be correlated with maternal plasma volume, fetal urine flow and AF volume in a longitudinal study of pregnant patients. Thirdly, we will determine the degree of maternal to fetal DDAVP transfer in pregnant subjects. Finally, the effects of DDAVP-induced plasma hypo-osmolality on fetal urine flow, AF volume and maternal plasma volume will be examined in patients with reduced AF volume, while determining the effects of DDAVP on maternal coagulation. These studies will potentially support a future study of chronic DDAVP-induced plasma-osmolality for pregnant patients with evidence of elevated plasma osmolality (i.e., failure to reset osmolality threshold). This proposal will aid in the development of markers of prediction and therapeutic approaches to the prevention and treatment of human oligohydramnios.

在正常人类妊娠早期，母体血浆渗透压降低，血浆容量增加。未能实现足够的血浆容量扩张与不良妊娠结局相关，包括羊水 (AF) 量减少（羊水过少）。羊水过少发生在所有妊娠的 8% 至 38% 中，并且与显着的围产期发病率和死亡率相关。我们最近的实验证实了胎盘渗透梯度在调节胎儿液体获取中的核心作用。我们已经确定，母体 DDAVP 和口服水给药会诱导母体和胎儿的生理反应，从而增加 AF 体积。具体来说，绵羊母体和胎儿血浆的低渗透压会增加母体血浆容量，并增加胎儿液体的获取、胎儿尿液的产生，从而增加 AF 体积。我们根据现有文献和我们的研究开发了一个概念模型，将母体血浆渗透压和精氨酸加压素 (AVP) 分泌阈值的重置、母体血浆容量扩张和 AF 容量暂时联系起来。我们的初步研究表明，空腹、早晨血浆渗透压/钠可用作 AVP 分泌的母体血浆渗透压阈值的简化“指数”，从而允许在整个妊娠期间重复确定阈值设定点。这些假设将在一系列逐步的人体研究中得到解决。首先，我们将建立血浆渗透压/钠设定点的简化指数对于非妊娠患者 AVP 分泌的效用，并将在妊娠期间妊娠患者的横断面研究中确认该指数。其次，在一项针对怀孕患者的纵向研究中，妊娠变化和血浆渗透压设定点的群体分布将与母体血浆容量、胎儿尿流量和房颤容量相关。第三，我们将确定妊娠受试者中 DDAVP 母体向胎儿转移的程度。最后，将在 AF 容量减少的患者中检查 DDAVP 诱导的血浆低渗透压对胎儿尿流量、AF 容量和母体血浆容量的影响，同时确定 DDAVP 对母体凝血的影响。这些研究可能支持未来对有血浆渗透压升高证据（即未能重置渗透压阈值）的妊娠患者进行慢性 DDAVP 诱导血浆渗透压的研究。该提案将有助于开发预防和治疗人类羊水过少的预测标记和治疗方法。