EFFECT OF SILDENAFIL ON UTERINE BLOOD FLOW IN NON-PREGNANT WOMEN

西地那非对非孕妇子宫血流的影响

• 批准号: 7605823
• 负责人: IRA MARK BERNSTEIN
• 金额: $ 0.38万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605823
• 关键词: Arteries; Blinded; Blood Vessels; Blood flow; Clinical; Clinical Investigator; Computer Retrieval of Information on Scientific Projects Database; Disease; Dose; Enzymes; Erectile dysfunction; Fetal Growth Retardation; Funding; Grant; Growth; Human; Institution; Localized; Lung; Measures; Organ; Patient currently pregnant; Pharmaceutical Preparations; Placenta; Pre-Eclampsia; Pregnancy; Pregnant Women; Protocols documentation; Pulmonary Hypertension; Purpose; Recruitment Activity; Relative (related person); Research; Research Personnel; Resources; Septic Toxemia; Source; Specificity; Standards of Weights and Measures; Transvaginal Ultrasound; United States National Institutes of Health; Uterus; Viagra; Woman; clinically significant; hemodynamics; improved; men; penis; phosphodiesterase V; reproductive; sildenafil

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During pregnancy, blood flow to the uterus (womb) and placenta must increase a lot to support a normal pregnancy. This is accomplished by a combination of blood vessel growth, the creation of new blood vessels, and an increased ability of existing blood vessels to open up. Several diseases of pregnancy such as preeclampsia (toxemia) and fetal growth restriction are associated with insufficient uterine blood flow, and there are no current therapies that can selectively improved uterine blood flow. In particular, there are no drugs that will increase blood flow to the uterus only; as most drugs that increase blood flow are relatively nonspecific and result in widespread increase in blood flow to all organs that ultimately results in a vascular redistribution that reduces blood flow to the uterus. Sildenafil (Viagra) has been used to increase blood flow to the penis in men (hence its use in improving erectile dysfunction). Its relative specificity derives from its ability to inhibit an enzyme, phosphodiesterase 5 (PDE5), which is not present everywhere in the body, but has been localized in the blood vessels of the reproductive organs, and in the vessels of the lung. The latter effect has been recognized as a potential therapy for pulmonary hypertension. Several recent studies have shown that sildenafil is also able to induce dilation of arteries isolated from the human uterus (see references, below), although it's hemodynamic effects on uterine blood flow have yet to be defined. The purpose of this study is to definitively answer this question by measuring uterine blood flow in nonpregnant women with transvaginal ultrasound. If a significant and specific effect is observed, we will consider extending these studies to women who are pregnant and, eventually, to those that have clinically significant reductions in uterine blood flow as are sometimes evident in preeclamptics. The pilot protocol will involve recruiting 30 nonpregnant women, 2/3 of whom will receive Sildenafil (split evenly among 2 different standard clinical doses), and 1/3 of whom will receive no medication is a manner that is blinded to the clinical investigator.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 怀孕期间，流向子宫和胎盘的血流量必须大量增加才能支持正常怀孕。 这是通过血管生长、新血管的产生以及现有血管开放能力的增强相结合来实现的。 一些妊娠疾病，如先兆子痫（毒血症）和胎儿生长受限与子宫血流不足有关，目前没有可以选择性改善子宫血流的治疗方法。 特别是，没有任何药物可以只增加子宫的血流量。因为大多数增加血流量的药物相对非特异性，会导致流向所有器官的血流量广泛增加，最终导致血管重新分布，从而减少流向子宫的血流量。 西地那非（伟哥）已被用于增加男性阴茎的血流量（因此可用于改善勃起功能障碍）。 其相对特异性源自其抑制磷酸二酯酶 5 (PDE5) 的能力，这种酶并不存在于体内各处，但只存在于生殖器官的血管和肺血管中。 后一种作用已被认为是肺动脉高压的潜在疗法。 最近的几项研究表明，西地那非还能够引起从人类子宫分离出来的动脉扩张（见下文参考文献），尽管它对子宫血流的血流动力学影响尚未确定。 本研究的目的是通过经阴道超声测量非孕妇的子宫血流量来明确回答这个问题。 如果观察到显着且具体的效果，我们将考虑将这些研究扩展到怀孕妇女，并最终扩展到那些临床上子宫血流量显着减少的妇女（有时在先兆子痫中很明显）。 试点方案将招募 30 名非孕妇，其中 2/3 将接受西地那非（平均分配为 2 种不同的标准临床剂量），其中 1/3 将不接受任何药物治疗，这种方式对临床研究人员是不知情的。