Seminars People Information Computing Research
Project I: Mechano-Electric Feedback in the Heart
P.I.s: Trayanova (Biomedical Engineering) and Fauci (Mathematics)
Despite the large body of research over the previous several decades, the mechanisms that underlie the initiation and maintenance of life-threatening cardiac arrhythmias are incompletely understood. For example, investigation into arrhythmogenesis has primarily focused into the electrical sources of excitation, such as ectopic foci and reentrant circuits. However, recent studies have demonstrated the contribution of mechano-electric feedback initiated by the abnormal mechanical loading of the heart. During ventricular fibrillation passive flow of blood from the left side of the heart into the right causes the right ventricular free wall to extend. Increased ventricular loading and the ensuing ventricular volume increase can engage stretch- activated ionic channels in the cardiac membrane. Opening of the stretch activated channels can cause shortening of the action potential and change in the velocity of propagation. Stretch can also be associated with a decrease in the refractory period, thus reducing the wavelength and making arrhythmias more likely to take place and be maintained. Clearly, the electrophysiological changes associated with tissue stretch will affect the dynamics of arrhythmia and fibrillation by modifying molecular transport mechanisms. Thus, the specific aim of this project is to further extend the scope of cardiac arrhythmogenisis and defibrillation by incorporating the contribution of mechano-electrical feedback into cardiac electrical behavior.
The hypothesis for this project is that passive mechanical loading of the heart during tachycardia and fibrillation engages stretch-activated channels in the cardiac membrane that leads to further proliferation of fibrillation and increases the fibrillation threshold. The proposed study will develop a sophisticated model of cardiac arrhythmogenic behavior and mechano-electric feedback that incorporates realistic geometry and fiber orientation in the heart, and membrane ionic mechanisms that integrate the engagement of stretch- activated channels and relate this to membrane stretch. The model will allow the investigation of the cross-talk between mechanical and electrical events that affects the initiation and maintenance of lethal arrhythmias in the heart. In this investigation, molecular transport through ionic channels is thus interrelated with macroscale (continuum) electrical conduction behavior and mechanical strain of cardiac tissue. Developing computational models of this multiscale phenomena will thus allow us to develop a quantitative link between fibrillation behavior and mechano-electrical responses of the heart due to mechanically mediated molecular transport behavior. For this project, we will develop links with research cardiologists and heart ion-transport cell biologists, as specified in the Development Project description. Thus, this collaboration between mathematicians, engineers and biomedical researchers will help to develop an understand fundamental cardiac disease mechanisms.
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Tulane Tulane University
201 Lindy Boggs Center
Computational Science
6823 St. Charles Ave.
New Orleans, LA 70118
(504)862-8391 ccs@tulane.edu