MATERNAL DEHYDRATION--FETAL/AMNIOTIC FLUID HOMEOSTASIS

母体脱水--胎儿/羊水稳态

• 批准号: 6182321
• 负责人: Michael Glenn Ross
• 金额: $ 21.14万
• 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/6182321
• 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.

与以下疾病相关的围产期发病率和死亡率显著 羊水过多和羊水过少是因为目前可用的治疗方法 疗效有限。然而，有效地减少羊水(AF) 早产儿早产的量和预防 羊水过多可降低新生儿发病率和死亡率。同样， 房颤减少的分娩患者增加房颤容量可改善胎儿 结果。拟议的研究将提出一些问题，包括 可能应用于临床的房颤容量改变策略 用于治疗羊水过多或过少。我们之前的研究提供了 母胎房水生理机制的有益认识 和电解液交换。而房颤是由多个站点的平衡来维持的 在液体的产生和吸收中，胎儿的尿流量是最多的 影响房颤量的重要部位。因此，尿流和尿量的改变 也许可以利用其他液体交换部位来调节房颤量。 我们开发了两个新颖的绵羊实验模型来改变房颤的体积， 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)。绵羊与人的初步研究 研究已经支持了这些潜在的临床应用。 干预措施。首先，我们假设羊水中的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及房颤量的减少。 羊膜腔内DDAVP是一种很有前途的治疗方法 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，胎儿尿流率显著增加，并扩张 房颤音量。因此，母体DDAVP是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 羊水(胎儿)DDAVP和母体DDAVP引起的低渗透压的关系。 生理学评估将重点放在胎儿液体交换的测量上 (尿流量、肺液、吞咽、胎盘扩散通透性) 和胎儿血浆和房颤的体积和组成在正常妊娠和 羊水过多和羊水过少的模型。我们还将衡量 胎儿和母体肾脏AVP受体亚群的DDAVP升高及其机制 其他体液调节激素(心钠素、肾素- 血管紧张素)。该项目的目标是确定安全和有效的 在多发性或多发性心脏病的情况下可以可靠地改变房颤容量的治疗方法 羊水过少。