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

电子烟

• 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
• 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

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.

怀孕期间子宫中的电子香烟蒸发和血管后遗症 尽管怀孕严重并发症，使用烟草产品的女性中有50％继续进行 因此在怀孕期间。 2017年最近的一项研究估计，许多妇女使用电子烟（E-cigs）作为 怀孕期间的常规香烟。这种令人震惊的数据的主要原因是传统烟草 用户将怀孕期间的VAP视为“更安全”的替代方案。但是，e-cig蒸气揭示了无数的 可能对母亲和胎儿有害的化学物质。 使用我们成熟的怀孕大鼠模型，我们获得了最先进的初步数据 定制设计的电子烟雾化器提供了翻译的吸入输送方法并产生的蒸气 剖面直接与人类烟相媲美。初步数据证明了电子烟引起的主要胎儿 生长不足，并为妊娠电路适应受损提供了第一个证据 血流，天然气和养分从母亲到胎儿的主要调节因子。 AIM＃1将测试是否蒸发电子烟 单独的碱（丙二醇：甘油的变化比）或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。此外，我们将测试是否有电子烟 怀孕期间诱导全身性心血管适应。我们将评估材料生殖 血管和电子烟引起的胎儿心血管适应，通过对肺系统的影响完成 利用高频超声检查，弹性，TTE，ECG，Luminex Xmap技术和手术 血压和基于微球的流动评估的导管插入术。 AIM＃2将测试Vaping E-cig是否会 通过内皮衍生的NO vs. EDHF与PGI2途径，子宫动脉放松受损（这三个） 血管扩张剂完全调节妊娠中原发子宫动脉血流）。我们将使用药品 使用压力动脉造影的内皮衍生的血管扩张途径的块组合，并剖析 使用HPLC，组织学方法，免疫印迹和其他分子工具受损的细胞信号传导受损。 我们的建议探讨了妊娠研究的新领域，开发了第一个机械框架 用于E-CIG蒸发引起的子宫回路适应，以提供转化吸入输送 和蒸气曲线可与人类雾化相提并论。提出的关于电子烟的健康影响的研究 怀孕将促进这些设备对公众构成潜在风险的适用政策实施。 拟议的研究直接介绍了最新的NIH/NHLBI研讨会的关键共识建议 关于心血管疾病和电子烟的出现，即研究电子烟气溶胶的作用 孕妇的暴露。