MATERNAL DEHYDRATION--FETAL/AMNIOTIC FLUID HOMEOSTASIS
母体脱水--胎儿/羊水稳态
基本信息
- 批准号:6536928
- 负责人:
- 金额:$ 36.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1989
- 资助国家:美国
- 起止时间:1989-04-01 至 2004-03-31
- 项目状态:已结题
- 来源:
- 关键词:RNase protection assay amniotic fluid arginine vasopressin blood volume body water dehydration drug screening /evaluation electrolyte balance embryo /fetus homeostasis hormone receptor hormone regulation /control mechanism hyponatremia in situ hybridization laboratory rat nonhuman therapy evaluation northern blottings placental transfer pregnancy pregnancy disorder chemotherapy prenatal stress radioimmunoassay scintillation counter sheep swallowing ultrasound blood flow measurement urinalysis
项目摘要
Amniotic fluid (AF) is an essential accompaniment of normal pregnancy,
necessary for fetal movement, growth and development. Oligohydramnios,
or reduced AF volume, occurs in 8 to 38 percent of all pregnancies. The
majority of oligohydramnios patients have no identifiable medical or
antepartum complication and only 7 percent of cases have associated
fetal malformations. However, oligohydramnios is often associated with
conditions of chronic fetal stress, such as intrauterine growth
retardation, preeclampsia and postterm pregnancy. These conditions,
together with the direct effect of reduced AF volume, results in
significant perinatal morbidity and mortality. Increasing AF volume in
laboring patients with oligohydramnios improves fetal outcome, though
this generally requires rupture of fetal membranes. However, our
studies demonstrate that modulation of AF production (fetal urine flow)
and AF resorption (fetal swallowing and intramembranous flow) may be
utilized to increase AF volume in patients with intact membranes. We
have developed a novel model to increase AF volume utilizing maternal
administration of the arginine vasopressin (AVP) antidiuretic agonist
[desamino, D-Arg8]-AVP (DDAVP). Our studies in the ovine model indicate
that maternal hydration and DDAVP induces maternal and fetal plasma
hyponatremia, marked increases in fetal urine flow, reduced fetal
swallowing and expansion of AF volume. Our human studies have supported
the clinical utility of these interventions. Despite these promising
results, critical issues of efficacy and safety of DDAVP therapy for
both the mother and fetus must be resolved prior to clinical use.
Firstly, in studies of efficacy, we will determine the minimum level of
maternal hyponatremia which induces and maintains fetal fluid responses,
and examine the effects of alterations in placental osmolality
gradients. Long term studies will examine the effects of hyponatremia
on ovine AF volume, maternal plasma volume and umbilical and uterine
blood flows in both normal and oligohydramnios ovine pregnancies.
Secondly, in studies of fetal safety, we will determine if fetal brain
edema and/or loss of brain electrolytes are induced by hyponatremia.
As AVP has important fetal fluid and cardiovascular regulatory roles,
we will determine the effect of hyponatremia on fetal osmotic and non-
osmotic stimulated AVP secretion. Finally, as permanent imprinting of
AVP synthesis and secretion regulatory systems may occur in response
chronic tonicity alterations in newborn rats, we will examine the
effects of chronic tonicity alterations on fetal AVP transcription and
translation. Physiologic assessments will focus on measurements of
fetal fluid exchange and fetal plasma and AF volume and composition.
Endocrine and molecular assessments will include determination of fluid
regulatory hormones and hypothalamic AVP mRNA and pituitary AVP
contents, utilizing our newly developed ovine 130 bp cDNA probe and
solution and in situ hybridization techniques. The goal of this project
is to determine critical efficacy and fetal safety issues central to
maternal DDAVP treatment, prior to widespread clinical use in human
pregnancies with oligohydramnios.
羊水(AF)是正常妊娠的基本伴随物,
对胎儿的运动、生长和发育是必要的。羊水过少,
或房颤体积减少,发生在所有怀孕的8%至38%。 的
大多数羊水过少患者没有可识别的医疗或
产前并发症,只有7%的病例
胎儿畸形 然而,羊水过少往往与
慢性胎儿应激的条件,如宫内生长
发育迟缓、先兆子痫和过期妊娠。 这些条件,
与AF体积减少的直接效果一起,导致
围产期发病率和死亡率很高。 增加AF音量
尽管羊水过少的分娩患者可以改善胎儿结局,
这通常需要胎膜破裂。 但我们的
研究表明调节AF产生(胎儿尿流)
和AF再吸收(胎儿吞咽和膜内血流)可能是
用于增加膜完整患者的AF体积。 我们
开发了一种新的模型,利用母体
精氨酸加压素(AVP)抗利尿剂激动剂的施用
[脱氨基,D-Arg 8]-AVP(DDAVP)。 我们对绵羊模型的研究表明,
母体水合作用和DDAVP诱导母体和胎儿血浆
低钠血症,胎儿尿流量明显增加,胎儿尿量减少
吞咽和AF体积扩大。 我们的人体研究支持了
这些干预措施的临床效用。 尽管有这些有希望
结果,DDAVP治疗的有效性和安全性的关键问题
在临床使用之前,必须解决母亲和胎儿的问题。
首先,在疗效研究中,我们将确定最低水平的
母体低钠血症诱导并维持胎儿体液反应,
并检测胎盘渗透压的改变
梯度。 长期研究将检查低钠血症的影响
对绵羊AF体积、母体血浆体积以及脐带和子宫的影响
正常和羊水过少绵羊妊娠期间的血液流动。
其次,在胎儿安全的研究中,我们将确定胎儿大脑是否
水肿和/或脑电解质损失由低钠血症引起。
由于AVP具有重要的胎儿体液和心血管调节作用,
我们将确定低钠血症对胎儿渗透压和非渗透压的影响,
渗透压刺激AVP分泌。 最后,作为永久的印记,
AVP的合成和分泌调节系统可能发生反应
新生大鼠的慢性张力改变,我们将研究
慢性张力改变对胎儿AVP转录的影响
翻译. 生理评估将侧重于测量
胎儿液体交换和胎儿血浆以及AF体积和组成。
内分泌和分子评估将包括测定液体
调节激素与下丘脑AVP mRNA和垂体AVP
内容,利用我们新开发的绵羊130 bp cDNA探针,
溶液和原位杂交技术。 这个项目的目标
是确定关键的疗效和胎儿安全问题,
母体DDAVP治疗,在人类临床广泛使用之前
妊娠合并羊水过少。
项目成果
期刊论文数量(67)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Osmotic threshold and sensitivity for vasopressin release and fos expression by hypertonic NaCl in ovine fetus.
- DOI:10.1152/ajpendo.2000.279.6.e1207
- 发表时间:2000-12
- 期刊:
- 影响因子:0
- 作者:Zhice Xu;Calvario Glenda;L. Day;Jiaming Yao;M. Ross
- 通讯作者:Zhice Xu;Calvario Glenda;L. Day;Jiaming Yao;M. Ross
A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulations.
具有脉动动脉循环的双胞胎输血综合征的数学模型。
- DOI:10.1152/ajpregu.00534.2006
- 发表时间:2007
- 期刊:
- 影响因子:0
- 作者:vandenWijngaard,JeroenPHM;Westerhof,BerendE;Ross,MichaelG;vanGemert,MartinJC
- 通讯作者:vanGemert,MartinJC
Twin-twin transfusion syndrome modeling.
双胎输血综合征模型。
- DOI:10.1196/annals.1389.010
- 发表时间:2007
- 期刊:
- 影响因子:5.2
- 作者:VANDENWijngaard,JeroenPHM;Ross,MichaelG;VANGemert,MartinJC
- 通讯作者:VANGemert,MartinJC
Fetal renal response to atrial natriuretic factor decreases with maturation.
胎儿肾脏对心房钠尿因子的反应随着成熟而降低。
- DOI:10.1152/ajpregu.1991.260.2.r346
- 发表时间:1991
- 期刊:
- 影响因子:0
- 作者:Castro,R;Ervin,MG;Leake,RD;Ross,MG;Sherman,DJ;Fisher,DA
- 通讯作者:Fisher,DA
Maternal dehydration: impact on ovine amniotic fluid volume and composition.
母体脱水:对绵羊羊水量和成分的影响。
- DOI:
- 发表时间:1990
- 期刊:
- 影响因子:0
- 作者:Schreyer,P;Sherman,DJ;Ervin,MG;Day,L;Ross,MG
- 通讯作者:Ross,MG
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Michael Glenn Ross其他文献
Michael Glenn Ross的其他文献
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{{ truncateString('Michael Glenn Ross', 18)}}的其他基金
Mechanisms of Programmed Gestational Hyperphagia
程序性妊娠期食欲过盛的机制
- 批准号:
7614207 - 财政年份:2008
- 资助金额:
$ 36.23万 - 项目类别:
Mechanisms of Programmed Gestational Hyperphagia
程序性妊娠期食欲过盛的机制
- 批准号:
7467418 - 财政年份:2008
- 资助金额:
$ 36.23万 - 项目类别:
Mechanisms of Programmed Gestational Hyperphagia
程序性妊娠期食欲过盛的机制
- 批准号:
7799747 - 财政年份:2008
- 资助金额:
$ 36.23万 - 项目类别:
Mechanisms of Programmed Gestational Hyperphagia
程序性妊娠期食欲过盛的机制
- 批准号:
8250374 - 财政年份:2008
- 资助金额:
$ 36.23万 - 项目类别:
Mechanisms of Programmed Gestational Hyperphagia
程序性妊娠期食欲过盛的机制
- 批准号:
8052762 - 财政年份:2008
- 资助金额:
$ 36.23万 - 项目类别:
DO IONIZED MAGNESIUM LEVELS PREDICT CLINICAL EFFECTS BETTER THAN TOTAL MAGNESIS
离子镁水平比总镁水平更能预测临床效果吗
- 批准号:
7606211 - 财政年份:2007
- 资助金额:
$ 36.23万 - 项目类别:
AQUAPORIN GENE EXPRESSION IN HUMAN FETAL MEMBRANE
人胎膜中水通道蛋白基因的表达
- 批准号:
7606210 - 财政年份:2007
- 资助金额:
$ 36.23万 - 项目类别:
AQUAPORIN GENE EXPRESSION IN HUMAN FETAL MEMBRANE
人胎膜中水通道蛋白基因的表达
- 批准号:
7376108 - 财政年份:2005
- 资助金额:
$ 36.23万 - 项目类别:
THE COMPARISON OF PLACENTAL AND UMBILICAL NUCLEATED RED BLOOD CELL COUNT
胎盘和脐带有核红细胞计数的比较
- 批准号:
7376109 - 财政年份:2005
- 资助金额:
$ 36.23万 - 项目类别:
THE COMPARISON OF PLACENTAL AND UMBILICAL NUCLEATED RED BLOOD CELL COUNT
胎盘和脐带有核红细胞计数的比较
- 批准号:
7206410 - 财政年份:2004
- 资助金额:
$ 36.23万 - 项目类别:
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