CAREER: The Effect of Physiological Pacing on Cardiac Dynamics

在这个项目中，PI将(1)通过模拟HRV将电恢复的概念扩展到真实的生理刺激的情况，以及(2)确定反馈调制对心脏从正常心律到异常心律转变的影响。主要的假设是，反馈的调节和消除导致了正常窦性心律的稳定，从而防止了心脏中异常心律的形成。修订后的电恢复概念将更准确地预测心脏向心律失常的转变。具体地说，PI建议：(1)通过包括生理性HRV来开发新的恢复概念，并测试在分离的心肌细胞中对这一新概念的预测；(2)通过对生理离子模型的数值模拟和全心光学映射实验来验证心脏组织中对新的恢复概念的预测；以及(3)使用在体大鼠模型来证明反馈调制对异常节律发展的有益效果。拟议的计划将在多学科环境中培训研究生和本科生，并将使学生接触到非线性思维方式。建议的活动将帮助学生获得使用非线性分析来理解工程和生物系统中的复杂性的能力。拟议的研究旨在最大限度地利用数值模拟和实验相结合的方法。不同水平的数值模拟和实验技术将有助于培训学生在不同的领域，并鼓励他们作为一个团队工作，以实现赠款的总体目标。作为教育计划的一部分，PI将开发一门适合科学与工程学院研究生和本科生的新课程，以加强他们对非线性动力学的接触。本课程将基于多层次的方法描述心脏的动力学，从单个离子电流到孤立的心肌细胞，再到整个心脏。研究项目的成果将被用来促进实践。在演示和实验室实验中学习。在研究生和本科生的帮助下，PI将设计一门心脏电生理学暑期实验室课程，帮助学生掌握几项技术，包括光学成像、数据采集、非线性信号分析和反馈控制。在接下来的几年里，PI将组织一个适合高中生的心脏动力学教育夏令营，在夏令营中，讲座和实验室课程都将根据他们的需求进行调整。

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.