In this project the PI will (1) to extend the concept of electrical restitution to the case of real physiological stimulation by mimicking HRV, and (2) to determine the effect of feedback modulation on the transition from normal to abnormal cardiac rhythms in the heart. The main hypothesis is that modulation and elimination of feedback leads to the stabilization of normal sinus rhythm, and therefore prevents abnormal rhythm formation in the heart. The revised concept of electrical restitution will be more accurate in predicting the transition to arrhythmias in the heart. Specifically, the PI proposes: (1) to develop a novel restitution concept by including a physiological HRV, and to test predictions of this new concept in isolated cardiac myocytes; (2) to validate predictions of the novel restitution concept in cardiac tissue using both numerical simulations of physiological ionic models and whole heart optical mapping experiments; and (3) to demonstrate the beneficial effect of feedback modulation on abnormal rhythm development using an in-vivo rat model. The proposed program will train graduate and undergraduate students in a multidisciplinary environment, and will expose students to nonlinear ways of thinking. The proposed activities will help students gain the ability to use nonlinear analyses to understand complexities in engineering and biological systems. The proposed research is designed to allow maximum use of combined numerical simulations and experimental approaches. Different levels of numerical simulations and experimental techniques will help train students in various areas, and encourage them to work as a team to accomplish the general objectives of the grant. As a part of educational program, the PI will develop a new course suitable for graduate and undergraduate students from the College of Science and Engineering to enhance their exposure to nonlinear dynamics. This course will describe the dynamics of the heart based on a multi-level approach, from single ionic current to isolated cardiac myocytes to the whole heart. The results of the research program will be used to promote ?hand-on? learning through demonstration and laboratory experiments. With the help of graduate and undergraduate students, the PI will design a Summer Lab course on cardiac electrophysiology to help students gasp several techniques, including optical imaging, data acquisition, nonlinear signal analysis, and feedback control. During next several years, the PI will organize an educational summer camp on cardiac dynamics adapted for high-school students, in which both lectures and lab course will be adapted for their needs.
