MATERNAL DEHYDRATION--FETAL/AMNIOTIC FLUID HOMEOSTASIS

有显着的围产期发病率和死亡率与 羊水过多和羊水过少，因为目前可用的治疗 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。同样地， 增加AF减少的分娩患者的AF体积可改善胎儿 结果。拟议的研究将提出一些问题， 改变AF体积的策略，可能在临床上应用 用于治疗羊水过多或过少。我们之前的研究提供了 对母胎AF水生理机制的有价值的见解 和电解质交换。而AF是由网站的平衡来维持的 胎儿尿流是液体产生和吸收的唯一最重要的因素， 影响AF体积的重要部位。因此，尿流的改变和 也许可以利用其它流体交换部位来调节AF体积。 我们已经开发了两种新颖的绵羊实验模型来改变AF体积， 每种都利用选择性精氨酸加压素（AVP）抗利尿剂 激动剂[脱氨基，D-Arg 8]-AVP（dDAVP）。初步绵羊和人 研究已经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 给药将导致胎儿血浆dDAVP水平升高， 胎儿尿液和肺液生成以及AF体积减少。 羊膜腔内dDAVP代表了一种有希望的治疗方法， 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将诱导母体和胎儿血浆 低渗透压，胎儿尿流率显著增加，以及扩张 AF的体积。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诱导的低渗透压。 生理评估将侧重于测量胎儿液体交换 （尿流量、肺液、吞咽、胎盘扩散渗透性） 和正常妊娠中的胎儿血浆和AF体积和组成， 羊水过多和过少的模型。我们还将测量 胎儿和母体肾脏AVP受体群体的dDAVP升高， 其他液体调节激素（心房利钠因子，肾素- 血管紧张素）。该项目的目标是确定安全有效的 治疗可以可靠地改变房颤体积， 羊水过少

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.