A foundation study of the effects of postnatal enalapril on maternal cardiac function following early-onset pre-eclampsia.

背景：先兆子痫（PE）是妊娠期的一种疾病，由高血压和尿液中的蛋白质共同引起。它影响3-5%的怀孕，对母亲和婴儿都有重大风险。早发性PE （EPE；发病于8个月前）的女性经常出现心功能异常，这增加了她们晚年患心脏病的风险。心脏功能的细微变化也被证明会增加女性下次怀孕时再次患PE的几率。尽管如此，迄今为止的研究都集中在怀孕上，对怀孕后会发生什么以及治疗是否能改善结果知之甚少。sFlt是一种阻止血管生长并导致血管收缩的蛋白质。在EPE中，sFlt水平升高，并与心功能异常程度相关。在动物研究中，sFlt已被证明直接导致心脏损伤，因此sFlt可能介导EPE相关的心脏损伤。血管紧张素转换酶（ACE）抑制剂通常用于防止心肌梗死后的心脏损伤，但从未对EPE后的使用进行过测试。Aims1。确定sFlt引起epe患者心脏损伤的机制。确定出生后服用ACE抑制剂是否可以逆转这种情况。目标1。目的探讨EPE后心功能异常的特征，并确定是否可以通过依那那治疗来改善。探讨sflt介导的pe样综合征动物模型心脏损伤的机制，并确定PN依那普利治疗是否能改善其作用。研究设计：人体研究。患有EPE的妇女将在分娩后6个月内随机分配依那普利或安慰剂。心脏功能将通过血液检查和超声扫描（超声心动图）来评估。这将使我们更多地了解EPE如何影响心脏（从安慰剂组），并测量依那普利对心脏的保护作用。动物模型研究。sFlt对怀孕大鼠心脏功能的影响将通过比较治疗和未治疗动物的心脏损伤标志物来测试。在此之后，我将测试依那普利在sFlt治疗动物出生后的疾病改善作用，使用一系列血液检查，心脏超声扫描和使用显微镜检查心脏。如果成功，这将是第一个为EPE引起的心脏损伤建立有效治疗方法的研究，并将在未来进行更长期的研究。这项研究也将为测试epe诱发的心脏病的替代疗法提供基础。妊娠后的早期干预可以减少PE的复发，并显著减少这一高危妇女群体心脏病的长期后果。

BackgroundPre-eclampsia (PE) is a condition in pregnancy, identified by a combination of high blood pressure and protein in the urine. It affects 3-5% of pregnancies and is associated with significant risks to mother and baby. Women with early-onset PE (EPE; onset before 8 months) frequently develop abnormal heart function, which increases their risk of heart disease in later life. Subtle changes in heart function have also been shown to increase the chance of a woman getting PE again in her next pregnancy. Despite this, research to date has focused on the pregnancy and relatively little is known about what happens after pregnancy and whether outcomes can be improved with treatment. sFlt is a protein that prevents blood vessel growth and causes blood vessel constriction. sFlt levels are raised in EPE and correlate with the degree of abnormal heart function. In animal studies, sFlt has been shown to directly cause injury to the heart and it is therefore possible that sFlt mediates EPE associated heart damage. Angiotensin converting enzyme (ACE) inhibitors are commonly used to protect against heart damage following myocardial infarction, but their use has never been tested following EPE. Aims1. Determine the mechanism by which sFlt causes heart injury in EPE.2. Determine whether this can be reversed with ACE inhibitors taken after birth. Objectives 1. To characterise abnormal heart function following EPE and determine if this can be modified by treatment with enalapril.2. To explore the mechanism of sFlt-mediated heart damage in an animal model of PE-like syndrome and determine if it can be ameliorated by PN enalapril treatment. Study designEPE (human) study. Women who have had EPE, will be randomly allocated to enalapril or placebo from delivery for 6 months. Heart function will be assessed using blood tests and ultrasound scans (echocardiography). This will allow us to learn more about how EPE affects the heart (from the placebo group) and measure the protective effect of enalapril on the heart. Animal model study. The effect of sFlt on the heart function of pregnant rats will be tested by comparing markers of heart damage in treated and untreated animals. Following this I will test the disease modifying effects of enalapril after birth in sFlt treated animals using serial blood tests, ultrasound scans of the heart and examination heart using microscopy.ImpactIf successful, this will be the first study to establish an effective treatment for the heart damage caused by EPE and will enable longer term studies in the future. This research will also provide foundations to test alternative treatments in EPE-induced heart disease. Early intervention after pregnancy could serve to reduce PE recurrence and dramatically reduce the long-term consequences of heart disease in this high-risk group of women.