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

CBET - 1342051

The 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).