ELECTRONIC CIGARETTE VAPING & VASCULAR SEQUELAE IN THE UTERUS DURING PREGNANCY

电子烟蒸发与妊娠期子宫血管后遗症 尽管有严重的妊娠并发症，50%使用烟草产品的女性仍将继续 所以在怀孕期间。最近2017年的一项研究估计，使用电子烟(电子烟)的女性人数与 怀孕期间的常规香烟。这一令人震惊的数据的一个主要原因是传统烟草 用户认为怀孕期间使用电子烟是一种“更安全”的选择。然而，电子烟蒸气显示出无数的 可能对母亲和胎儿都有害的化学物质。 使用我们建立的怀孕大鼠模型，我们利用最先进的技术获得了初步数据 定制设计的e-cig雾化器，提供平移吸入输送方法并产生蒸汽 可直接与人体蒸发相媲美。初步数据显示，e-cig诱导的主要胎儿 生长缺陷，并为包括子宫在内的妊娠循环适应受损提供了第一个证据 血液流动，从母亲到胎儿的气体和营养输送的主要调节器。目标1将测试蒸发电子烟是否 基础(丙二醇：甘油的不同比例)单独或随着尼古丁剂量的增加而产生剂量- 对子宫血流量(UBF)和胎儿生长反应的依赖效应。此外，我们会测试是否有电子烟- 孕期诱导的全身心血管适应。我们将评估母亲的生殖能力 血管和e-CIG诱导的胎儿心血管适应，并伴随着对肺部系统的影响 利用高频超声、FlexiVent、TTE、心电、Luminex xMAP技术和外科 血压导管术和基于微球的血流评估。目标2将测试Vaping e-cig是否 通过内皮来源的NO、EDHF和PGI2途径损害子宫动脉的舒张性(三种途径 完全调节妊娠期间主要子宫动脉血流的血管扩张剂)。我们会在药理学上 使用加压动脉造影术阻断内皮源性血管扩张剂途径的组合，并解剖 利用高效液相色谱、组织学方法、免疫印迹和其他分子工具损害细胞信号。 我们的建议探索了孕育研究的新前沿，开发了第一个机械框架 在提供平移吸入的模型中，用于e-cig汽化诱导的子宫循环适应 以及类似于人体蒸发的蒸气轮廓。关于电子烟对健康影响的拟议研究 怀孕将有助于就这些设备对公众构成的潜在风险执行适用的政策。 拟议的研究直接涉及NIH/NHLBI最近一次研讨会的一项关键共识建议 关于心血管疾病和电子烟的出现，即调查电子烟气雾剂的影响 孕妇暴露在空气中。

ELECTRONIC CIGARETTE VAPING & VASCULAR SEQUELAE IN THE UTERUS DURING PREGNANCY Despite serious pregnancy complications, 50% of women who use tobacco products will continue to do so during pregnancy. A recent 2017 study estimates as many women use electronic-cigarettes (e-cigs) as conventional cigarettes during pregnancy. One major reason for this alarming data is that traditional tobacco users view vaping during pregnancy as a “safer” alternative. However, e-cig vapor reveals a myriad of chemicals which may be harmful to both the mother and the fetus. Using our well-established pregnant rat model, we obtained preliminary data utilizing a state-of-the-art custom-engineered e-cig atomizer that offered a translational inhalation delivery method and generated vapor profiles directly comparable to human vaping. The preliminary data demonstrated e-cig-induced major fetal growth deficit and provides the first evidence for impaired gestational circulatory adaptations including uterine blood flow, the prime regulator of gas and nutrient delivery from mother to fetus. Aim#1 will test if vaping e-cig base (varying ratios of propylene glycol: glycerol) alone or with increasing doses of nicotine produce a dose- dependent effect on uterine blood flow (UBF) and fetal growth response. Further, we will test if there are e-cig- induced systemic cardiovascular adaptations during pregnancy. We will assess maternal reproductive vascular, and e-cig-induced fetal cardiovascular adaptations, accompanied by effects on the pulmonary system utilizing high frequency ultrasonography, flexiVent, TTE, ECG, Luminex xMAP technology, and surgical catheterization for blood pressure and microsphere-based flow assessment. Aim#2 will test if vaping e-cig will impair uterine artery relaxation via the endothelium-derived NO vs. EDHF vs. PGI2 pathways (the three vasodilators that entirely regulate primary uterine artery blood flow in pregnancy). We will pharmacologically block combinations of endothelial-derived vasodilator pathways using pressure arteriography, and dissect impaired cell signaling utilizing HPLC, histological approaches, immunoblotting, and other molecular tools. Our proposal explores a new frontier of gestational research developing the first mechanistic framework for e-cig vaping-induced uterine circulatory adaptations in a model that offers a translational inhalation delivery and vapor profiles comparable to human vaping. The proposed studies on the health effects of e-cigs during pregnancy will facilitate applicable policy implementation on potential risks these devices pose to the public. Proposed studies directly address a key consensus recommendation of the most recent NIH/NHLBI workshop on cardiovascular disease and the emergence of e-cigs, i.e. investigating effects of e-cigarette aerosol exposure in pregnant women.