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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 在怀孕期间，流向子宫（子宫）和胎盘的血液必须增加很多，以支持正常怀孕。 这是通过血管生长、新血管的产生和现有血管开放能力的提高来实现的。 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，目前还没有可以选择性改善子宫血流的治疗方法。 特别是，没有药物只会增加流向子宫的血流量;因为大多数增加血流量的药物都是相对非特异性的，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，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（因此其用于改善勃起功能障碍）。 其相对特异性来自其抑制酶磷酸二酯酶5（PDE 5）的能力，磷酸二酯酶5并不存在于身体的各处，而是定位于生殖器官的血管和肺的血管中。 后一种效应已被认为是肺动脉高压的潜在治疗方法。 最近的几项研究表明，西地那非也能够诱导从人子宫分离的动脉扩张（见下文参考文献），尽管其对子宫血流的血液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妊娠妇女的子宫血流来明确回答这个问题。 如果观察到显著和特异性的影响，我们将考虑将这些研究扩展到妊娠妇女，并最终扩展到子宫血流量临床显著减少的妇女，这在先兆子痫中有时很明显。 试验方案将招募30名非妊娠女性，其中2/3将接受西地那非（平均分配至2种不同的标准临床剂量），其中1/3将不接受药物治疗，这是对临床研究者设盲的方式。

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.