ELECTRONIC CIGARETTE VAPING & VASCULAR SEQUELAE IN THE UTERUS DURING PREGNANCY.

电子烟蒸汽和血管后遗症在子宫在怀孕期间 尽管有严重的妊娠并发症，50%的使用烟草产品的妇女将继续这样做， 所以在怀孕期间。2017年的一项研究估计，使用电子烟的女性人数与使用电子烟的女性人数一样多， 在怀孕期间吸烟。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，电子烟蒸汽揭示了无数的 可能对母亲和胎儿都有害的化学物质。 使用我们完善的妊娠大鼠模型，我们利用最先进的 定制设计的电子烟雾化器，其提供平移吸入递送方法并产生蒸汽 与人类吸电子烟的情况直接相当。初步数据表明，电子烟诱导的主要胎儿 生长缺陷，并提供了第一个证据，损害妊娠循环适应，包括子宫 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将测试是否vaping电子烟 碱（不同比例的丙二醇：甘油）单独或与增加剂量的尼古丁产生剂量- 对子宫血流（UBF）和胎儿生长反应的依赖性影响。另外，我们将测试是否有电子烟- 在怀孕期间诱导全身性心血管适应。我们将评估产妇的生殖 血管和电子烟诱导的胎儿心血管适应，伴随着对肺系统的影响 利用高频超声、flexiVent、TTE、ECG、Luminex xMAP技术和外科手术 用于血压和基于微球的血流评估的导管插入术。目标#2将测试电子烟是否会 通过内皮源性NO与EDHF与PGI 2途径损害子宫动脉舒张（这三种途径 在妊娠期完全调节子宫动脉血流的血管扩张剂）。我们将 使用压力动脉造影术阻断内皮源性血管扩张剂通路的组合， 利用HPLC、组织学方法、免疫印迹和其他分子工具检测受损细胞信号传导。 我们的建议探索了一个新的前沿妊娠研究发展的第一个机制框架 对于在提供平移吸入递送的模型中的电子烟蒸汽诱导的子宫循环适应， 和与人类吸电子烟相当的蒸汽特征。建议研究电子烟对健康的影响， 怀孕将有助于实施有关这些设备对公众构成的潜在风险的适用政策。 拟议的研究直接解决了最近NIH/NHLBI研讨会的关键共识建议 心血管疾病和电子烟的出现，即调查电子烟气雾剂的影响 孕妇接触。

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.