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

电子烟

基本信息

批准号：
10540752
负责人：
Jayanth Ramadoss
金额：
$ 38.84万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-05 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10540752
关键词：
Address Arteries Arteriographies Atomizer Birth Weight Blood Pressure Blood Vessels Blood flow Cardiac Output Cardiovascular Diseases Cardiovascular system Catheterization Chemicals Consensus Custom Data Devices Dose Educational workshop Electrocardiogram Electronic cigarette Endothelium Engineering Enzymes Epoprostenol Fetal Development Fetal Growth Fetal Growth Retardation Fetal health Fetus Frequencies Gases General Population Glycerol Health High Pressure Liquid Chromatography Histologic Human Impairment Inhalation Knowledge Liquid substance Lung Maternal Health Methods Microspheres Modeling Molecular Mothers NOS3 gene National Heart, Lung, and Blood Institute Neonatal Nicotine Nitric Oxide Nutrient Operative Surgical Procedures Outcome Oxygen Pathway interactions Policies Positioning Attribute Pregnancy Pregnancy Complications Pregnant Women Production Propylene Glycols Public Health Rattus Recommendation Relaxation Research Risk Signal Transduction Smoking Surgeon System Technology Testing Tobacco use Ultrasonography United States National Institutes of Health Uterus Vascular Diseases Vasodilator Agents Western Blotting Woman base combustible cigarette commercialization design e-cigarette aerosols electronic cigarette use exposed human population fetal frontier hemodynamics indexing pharmacologic pregnant pressure protein expression public education reproductive response tobacco user tool transcriptome vaping vapor vascular injury

项目摘要

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.

怀孕期间使用电子烟和子宫血管后遗症尽管存在严重的妊娠并发症，但 50% 使用烟草制品的女性仍会继续这样做 2017 年最近的一项研究估计，在怀孕期间使用电子烟的女性数量与怀孕期间吸烟的一个主要原因是传统烟草。用户认为怀孕期间吸电子烟是一种“更安全”的选择，然而，电子烟蒸汽揭示了无数的秘密。可能对母亲和胎儿都有害的化学物质。使用我们完善的怀孕大鼠模型，我们利用最先进的方法获得了初步数据定制设计的电子烟雾化器，提供平移吸入输送方法并产生蒸汽初步数据表明电子烟对胎儿有直接影响。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流是母亲向胎儿输送气体和营养的主要调节器，Aim#1 将测试是否吸电子烟。单独使用碱（不同比例的丙二醇：甘油）或与增加剂量的尼古丁一起产生剂量- 对子宫血流量（UBF）和胎儿生长反应的依赖性影响此外，我们将测试是否存在电子烟- 我们将评估孕产妇的生殖能力。血管和电子烟引起的胎儿心血管适应，并伴有对肺系统的影响利用高频超声检查、flexiVent、TTE、ECG、Luminex xMAP 技术和手术血压插管和基于微球的流量评估将测试电子烟是否有效。通过内皮源性 NO、EDHF 和 PGI2 途径（三种途径）损害子宫动脉舒张我们将在药理学上完全调节妊娠期子宫动脉血流的血管扩张剂）。使用压力动脉造影阻断内皮源性血管舒张途径的组合，并解剖利用 HPLC、组织学方法、免疫印迹和其他分子工具检测细胞信号传导受损。我们的提案探索了妊娠研究的新领域，开发了第一个机械框架在提供平移吸入输送的模型中研究电子烟引起的子宫循环适应和与人类吸电子烟相当的蒸汽分布。拟议的关于电子烟对健康影响的研究。怀孕将有助于针对这些设备对公众造成的潜在风险实施适用政策。拟议的研究直接针对最近 NIH/NHLBI 研讨会的关键共识建议对心血管疾病和电子烟的出现，即研究电子烟气溶胶的影响孕妇的暴露。