The Role of E-cigarette Characteristics and Constituents in Cardiac Dysfunction--Diversity Supplement

电子烟特性和成分在心脏功能障碍中的作用--多样性补充

• 批准号: 10005694
• 负责人: Alex Perrow Carll
• 金额: $ 1.87万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-05 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005694
• 关键词: Acute; Adverse effects; Aerosols; Affect; Aldehydes; Animals; Area; Arrhythmia; Biochemical; Biochemistry; Biological Assay; Biological Markers; Blood Pressure; Cardiac; Cardiac Electrophysiologic Techniques; Cardiac health; Cardiotoxicity; Cardiovascular system; Characteristics; Chronic; Data; Devices; Echocardiography; Electric Stimulation; Electrocardiogram; Electrodes; Electronic cigarette; Electrophysiology (science); Exposure to; Failure; Female; Functional disorder; Gap Junctions; Gene Expression; Generations; Glycerol; Goals; Harm Reduction; Health; Health Policy; Heart; Heart Atrium; Histologic; Histopathology; Human; Inhalation; Ion Channel; Mainstreaming; Measures; Mission; Molecular; Monitor; Mus; Myocardial dysfunction; Nicotine; Outcome; Particulate Matter; Pattern; Periodicity; Physiology; Policies; Predisposition; Production; Propylene Glycols; Public Health; Refractory; Regimen; Research; Research Personnel; Research Priority; Risk; Role; Safety; Smoking; Solvents; Stimulus; Structure; Telemetry; Testing; Time; Tissues; Toxic effect; United States National Institutes of Health; Vegetables; Ventricular; Western Blotting; Work; aerosolized; air filter; atrioventricular node; authority; cardiovascular health; cigarette smoke; cigarette smoking; combustible cigarette; design; disability; e-cigarette aerosols; electronic cigarette use; heart function; heart rate variability; hemodynamics; insight; interest; male; novel; sex; urinary

ABSTRACT E-cigarettes (e-cigs) have become increasingly popular, but their acute and chronic health effects are mostly unknown. Conventional cigarette smoking increases the risk of cardiac arrhythmia by slowing ventricular repolarization and inducing QT interval prolongation on the electrocardiogram (ECG). E-cigs produce several of the harmful and potentially harmful constituents (HPHCs) found in cigarette smoke. When aerosolized, the e-cig solvents propylene glycol (PG) and vegetable glycerin (VG), may similarly affect repolarization. Our preliminary data indicate exposure to e-cig solvent aerosols of equal-ratio PG and VG (PG:VG) prolongs QT and alters gene expression of ion channels key for repolarization in the mouse heart, suggesting inhalation of e-cig solvent aerosols may convert the heart into an arrhythmogenic substrate. However, e-cigs produce HPHCs at levels that vary markedly according to device characteristics, operating conditions, and use patterns. Thus, the full spectrum of their health impacts remains unclear. This project is designed to identify specific device characteristics and e-cig constituents associated with cardiac toxicity. It will apply both ECG and programmed stimulus electrophysiology (EP) studies to test the hypothesis that e-cigs induce electrical disturbances in the heart and that these effects depend upon e-cig characteristics and constituents. The studies will 1: Determine how device characteristics influence the acute electrophysiologic effects of e-cigs in mice, and 2: Assess the impacts of chronic e-cig exposure on cardiac electrophysiology and hemodynamics. Real-time cardiac physiology will be monitored through ECG telemetry during and after acute exposures to PG:VG aerosols from e-cigs of various characteristics (device type, user settings, nicotine levels), to delineate how they affect both HPHC production and ECG measures of cardiac dysfunction. The device characteristics with the greatest and slightest acute cardiac effects will then be selected for chronic exposure studies, in which cardiac EP and hemodynamics will be comprehensively assessed through telemetry, echocardiography, programmed electrical stimulation of the heart, molecular and histologic assays, aerosol assessments of HPHCs, and analyses of biomarkers of HPHC exposures. All exposure groups will be simultaneously compared to cigarette smoke and filtered-air exposure groups. Our research plan is responsive to the research priorities of the FDA/CTP, especially the interest area of toxicity. We expect that our results will elucidate the relative toxicity of different e-cig devices, constituents, and settings, and provide novel and significant insights into how each influences the arrhythmogenic potential of e-cig aerosols. We believe the outcome of our project would provide comprehensive and rigorous data to guide policies on e-cig product standards and to inform regulatory authorities of the cardiac risks associated with specific e-cig constituents and characteristics.

抽象的 电子烟（e-cigs）越来越受欢迎，但其急性和慢性健康影响 大多不为人知。传统吸烟会减慢心律失常的风险 心室复极和诱导心电图 (ECG) 上的 QT 间期延长。电子烟 产生香烟烟雾中发现的多种有害和潜在有害成分 (HPHC)。 当雾化时，电子烟溶剂丙二醇（PG）和植物甘油（VG）同样可以 影响复极化。我们的初步数据表明暴露于等比例 PG 的电子烟溶剂气溶胶 VG (PG:VG) 延长 QT 并改变离子通道的基因表达，这些离子通道对于复极至关重要 小鼠心脏，表明吸入电子烟溶剂气溶胶可能会将心脏转变为致心律失常的 基材。然而，电子烟产生的 HPHC 水平因设备而异 特性、操作条件和使用模式。因此，它们对健康的全方位影响 仍不清楚。该项目旨在识别特定的设备特征和电子烟成分 与心脏毒性有关。它将应用心电图和程序刺激电生理学 (EP) 研究检验电子烟引起心脏电干扰的假设，以及这些影响 取决于电子烟的特性和成分。研究将 1：确定设备如何 特征影响电子烟对小鼠的急性电生理效应，2：评估 长期接触电子烟对心脏电生理学和血流动力学的影响。即时的 在急性暴露于 PG:VG 期间和之后，将通过心电图遥测监测心脏生理机能 具有各种特征（设备类型、用户设置、尼古丁含量）的电子烟中的气溶胶，以描述如何 它们影响 HPHC 的产生和心功能障碍的心电图测量。设备特点 然后将选择具有最大和最轻微急性心脏影响的慢性暴露研究， 通过遥测技术对心脏EP和血流动力学进行综合评估， 超声心动图、心脏程序电刺激、分子和组织学检测、 HPHC 的气溶胶评估以及 HPHC 暴露的生物标志物分析。所有暴露组 将同时与香烟烟雾和过滤空气暴露组进行比较。我们的研究计划是 响应 FDA/CTP 的研究重点，特别是毒性的兴趣领域。我们期望 我们的结果将阐明不同电子烟设备、成分和设置的相对毒性，以及 提供关于每种因素如何影响电子烟致心律失常潜力的新颖且重要的见解 气溶胶。我们相信我们的项目成果将提供全面而严格的数据来指导 电子烟产品标准政策，并向监管机构通报与电子烟相关的心脏风险 具体的电子烟成分和特征。