EAGER: Analysis of cardiac repolarization as a tool for the noninvasive assessment of cardiovascular system exposure to carbon and metallic nanotubes

EAGER：心脏复极分析作为无创评估心血管系统暴露于碳和金属纳米管的工具

• 批准号: 1342051
• 负责人: Joseph Starobin
• 金额: $ 10万
• 依托单位: University of North Carolina Greensboro
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1342051&HistoricalAwards=false
• 关键词: EAGER; Analysis; cardiac; repolarization; tool

CBET - 1342051The research goal of this proposal is to investigate a feasibility of measurements of cardiac repolarization as a tool for the noninvasive assessment of cardiovascular system exposure to carbon and metallic nanotubes. In pursuit of this goal, the specific objectives are to:(a) employ an intensity-controlled dobutamine exercise stress test for the conscious rats after pulmonary exposure to single-wall carbon and TiO2 nanotubes, and determine values of QT/RR hysteresis and the rates of adaptation of QT and RR intervals, (b) use common bio- and immunochemical markers and determine the degree of toxic levels of oxidative stress, myocyte injury and vascular inflammation, and (c) compare the association of toxic outcomes of pulmonary exposure to different nanotubes using electrophysiological and immunochemical markers. The unique aspect of this proposal is the integration of theoretical nonlinear dynamics and experimental electrophysiological measurements to assess toxicological effects of nanostructures on cardiac function. Successful accomplishment of the above objectives will have far-reaching implications in the development of robust noninvasive monitoring of cardio toxicity of nano-systems. The educational goals of this proposal are to integrate new science and technology into formal and informal teaching and outreach programs in an effective manner. We extend a cohesive educational plan with three major themes: Course development, Mentoring, and Outreach activities. (A) Improve two graduate-level courses: NANO785 - Fundamentals of Nanobioelectronics (S. Aravamudhan), NAN740 - Nonlinear Waves in Biological Excitable Media (J. Starobin), through incorporation of research results. (B) Involvement of graduate and undergraduate students (including minority graduate students, currently working with the PI) in the interdisciplinary fields with significant exposure to materials, bioelectronics, biology and computational physics, (C) Current and future outreach programs at NCA&T, UNCG and JSNN will be strengthened (including NanoDay and K-12 Nanotechnology Lego modules).Intellectual Merit :Previous research demonstrated the importance of biochemical and immunological markers for identifying nanotube induced oxidative stress and vascular damage. However, the association of such exposure with noninvasive electrophysiological factors is not understood. Even if monitoring of cardiovascular system using electrophysiological measurements is one of the most robust biomedical tools it is still not adapted for applications in the environmental studies which is of a critical importance for public health. This project will pave the road for the development of novel non-invasive electrographic predictors of toxic effects on human cardiovascular system.Broader Impacts :This research seeks to enhance diversity in the emerging cross-disciplinary areas of nanobioscience by training graduate and undergraduate students, especially minorities and women in both NCA&T and UNCG. In addition to formal education, it will enrich established partnerships with Guilford County schools and technical community colleges. Also, the results of this research will be widely disseminated to the public through both formal modes and on a dedicated YouTube channel (to be launched soon by JSNN).

CBET -1342051本提案的研究目标是研究心脏复极测量作为无创评估心血管系统暴露于碳和金属纳米管的工具的可行性。为了实现这一目标，具体目标是：（a）在肺暴露于单壁碳和TiO 2纳米管后，对清醒大鼠进行强度控制的多巴酚丁胺运动应激试验，并确定QT/RR滞后值以及QT和RR间期的适应率，（B）使用常见的生物和免疫化学标记物，并确定氧化应激、肌细胞损伤和血管炎症的毒性水平的程度，以及（c）使用电生理和免疫化学标记物比较肺暴露于不同纳米管的毒性结果的相关性。该提案的独特之处在于将理论非线性动力学和实验电生理测量相结合，以评估纳米结构对心脏功能的毒理学影响。上述目标的成功实现将对纳米系统心脏毒性的稳健无创监测的发展产生深远的影响。这项建议的教育目标是以有效的方式将新的科学和技术融入正式和非正式的教学和推广计划。我们扩展了一个有三大主题的有凝聚力的教育计划：课程开发，指导和推广活动。(A)改进两个研究生水平的课程：NANO 785-纳米生物电子学基础（S。Aravamudhan），NAN 740-生物可激发介质中的非线性波（J. Starobin），通过结合研究结果。(B)研究生和本科生（包括少数民族研究生，目前与PI合作）参与跨学科领域，大量接触材料，生物电子学，生物学和计算物理学，（C）将加强NCA T，UNCG和JSNN的当前和未来推广计划&（包括NanoDay和K-12纳米技术乐高模块）。智力优点：先前的研究表明，生物化学和免疫学标记物对于识别纳米管诱导的氧化应激和血管损伤的重要性。然而，这种暴露与非侵入性电生理因素的关联尚不清楚。即使使用电生理测量监测心血管系统是最强大的生物医学工具之一，它仍然不适合在环境研究中的应用，这是一个至关重要的公共卫生。该项目将铺平道路，为开发新的非侵入性心电图预测对人体心血管系统的毒性作用。更广泛的影响：这项研究旨在通过培训研究生和本科生，特别是少数民族和妇女在NCA T和UNCG的纳米生物科学的新兴跨学科领域的多样性。除了正规教育外，它还将丰富与吉尔福德县学校和技术社区学院建立的伙伴关系。此外，这项研究的结果将通过正式模式和专门的YouTube频道（不久将由JSNN推出）向公众广泛传播。