MATERNAL DEHYDRATION--FETAL/AMNIOTIC FLUID HOMEOSTASIS

母体脱水--胎儿/羊水稳态

• 批准号: 6086773
• 负责人: Michael Glenn Ross
• 金额: $ 2.28万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6086773
• 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

There is significant perinatal morbidity and mortality associated with polyhydramnios and oligohydramnios because currently available therapies have limited efficacy. Yet, effective reduction of amniotic fluid (AF) volume and prevention of preterm delivery in pregnancies with polyhydramnios reduces neonatal morbidity and mortality. Similarly, increasing AF volume in laboring patients with reduced AF improves fetal outcome. The proposed studies will ask a number of questions about strategies to alter AF volume which potentially may be applied clinically for treatment of poly- or oligohydramnios. Our previous studies provided valuable insight into physiologic mechanisms of maternal-fetal-AF water and electrolyte exchange. Whereas AF is maintained by a balance of sites of fluid production and resorption, fetal urine flow is the single most important site influencing AF volume. Thus, alterations in urine flow and perhaps other fluid exchange sites may be utilized to modulate AF volume. We have developed two novel, ovine experimental models to alter AF volume, each utilizing the selective arginine vasopressin (AVP) antidiuretic agonist [desamino, D-Arg8]-AVP (dDAVP). Preliminary ovine and human studies have supported the potential clinical utility of these interventions. Firstly, we hypothesize that intraamniotic dDAVP administration will result in increased fetal plasma dDAVP levels, reduced fetal urine and lung fluid production and decreased AF volume. Intraamniotic dDAVP represents a promising treatment for patients with polyhydramnios. Secondly, as the antithesis of dehydration we hypothesize that maternal intravenous dDAVP will induce maternal and fetal plasma hypo-osmolality, marked increases in fetal urine flow rates, and expansion of AF volume. Thus maternal dDAVP represents a potential therapy for patients with oligohydramnios. We will explore acute and chronic effects of intraamniotic (fetal) dDAVP and maternal dDAVP-induced hypo-osmolality. Physiologic assessments will focus on measurements of fetal fluid exchange (urine flow, lung liquid, swallowing, placenta diffusion permeabilities) and fetal plasma and AF volume and composition in normal pregnancies and models of poly- and oligohydramnios. We also will measure the effects of elevated dDAVP on fetal and maternal renal AVP receptor populations and on other fluid regulatory hormones (atrial natriuretic factor, renin- angiotensin). The goal of this project is to identify safe and effective treatments which can reliably alter AF volume in cases of poly- or oligohydramnios.

与以下因素相关的围产期发病率和死亡率显着 羊水过多和羊水过少，因为目前可用的治疗方法 功效有限。然而，有效减少羊水（AF） 孕妇早产的数量和预防 羊水过多可降低新生儿发病率和死亡率。相似地， 增加 AF 减少的临产患者的 AF 体积可改善胎儿 结果。拟议的研究将提出一些关于 改变 AF 体积的策略可能会应用于临床 用于治疗羊水过多或羊水过少。我们之前的研究提供了 对母胎 AF 水生理机制的宝贵见解 和电解质交换。而 AF 是通过站点平衡来维持的 在液体产生和吸收过程中，胎儿尿流量是最大的 影响 AF 体积的重要部位。因此，尿流量和 也许其他液体交换位点可用于调节 AF 容量。 我们开发了两种新颖的绵羊实验模型来改变 AF 体积， 每种药物都使用选择性精氨酸加压素 (AVP) 抗利尿剂 激动剂[去氨基，D-Arg8]-AVP (dDAVP)。初步的绵羊和人类 研究支持了这些药物的潜在临床效用 干预措施。首先，我们假设羊膜内 dDAVP 给药会导致胎儿血浆 dDAVP 水平升高，降低 胎儿尿液和肺液的产生以及房颤体积的减少。 羊膜腔内 dDAVP 对于患有以下疾病的患者来说是一种有前景的治疗方法 羊水过多。其次，作为脱水的对立面，我们假设 母体静脉注射 dDAVP 会诱导母体和胎儿血浆 低渗透压、胎儿尿流量显着增加和扩张 AF 音量。因此，母体 dDAVP 代表了一种潜在的治疗方法 羊水过少的患者。我们将探讨急性和慢性影响 羊膜内（胎儿）dDAVP 和母体 dDAVP 引起的低渗透压的影响。 生理评估将重点关注胎儿液体交换的测量 （尿流量、肺液体、吞咽、胎盘扩散渗透性） 正常妊娠时胎儿血浆和 AF 的体积和成分 羊水过多和羊水过少的模型。我们还将衡量以下因素的影响 胎儿和母体肾脏 AVP 受体群体的 dDAVP 升高 其他体液调节激素（心房钠尿因子、肾素 血管紧张素）。该项目的目标是确定安全有效的 在多发或多发情况下，可以可靠地改变 AF 体积的治疗方法 羊水过少。