This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. (A) OBJECTIVES In ventricular fibrillation (VF), the leading cause of sudden cardiac death, the wave of electrical activation breaks up into a multi-wave chaotic state. Our research has focused on the question: what are the causes of this wavebreak? The traditional view was that the wave was broken up by anatomic heterogeneity, such as the curved ventricular and septal walls with their varying thicknesses, and the systematically varying anisotropy that is seen as one proceeds transmurally across the myocardial walls. The objective of our earlier research was to answer the questions: how important are anatomical heterogeneities as opposed to purely dynamical instabilities in generating and sustaining fibrillation? How do they interact? We have now shown that while the anatomic factors above can play contributory roles, the decisive role is played by the dynamical stability of conduction, which is determined by the electrophysiologic properties of the cells and tissue. We now propose to extend this research to consider the anatomic and electrophysiologic changes that are seen in heart failure.
Our Specific Aims are to study arrhythmias in heart failure, and especially to tease apart the contributions to arrhythmia generation made by abnormal anatomy, on the one hand, and abnormal cell electrophysiology, on the other. To study this, we will study the normal cell in the abnormal structural heart, the abnormal cell in the normal heart and then the two pathologies, cell and tissue, together. We will use the three-dimensional ventricular anatomic models and tools developed by the NBCR investigators, and by us in conjunction with NBCR researchers, to study these questions.
Specific Aim 1 : To use the rabbit Virtual Heart to test the effects on cardiac wave conduction produced by adding such pathological factors as fibrosis, infarct scars, and loss of cell-to-cell electrical coupling.
Specific Aim 2 : To use the NBCR modeling environment to study the effects of alterations in intracellular calcium handling on the genesis and maintenance of VF. The UCSD cell systems modeling environment, coupled to the geometry models, are the ideal platforms on which to test our hypotheses that altered intracellular calcium handling is a key to the genesis of fibrillation in heart failure.
Specific Aim 3 : To develop anatomically realistic models of several forms of heart failure in the rabbit, and use those models together with our cell models for normal and heart failure rabbit, to test the relative contributions of altered tissue structure vs. altered cell electrophysiology, in the genesis of arrhythmias in heart failure. The proposed collaborative research will provide a driving application for the new developments in software and computational methods in Specific Aims 1 of Core [4A.2B], and the resulting new anatomic and electrophysiological meshes and models will be shared with the community via the database to be developed in Specific Aim 2. It will serve as a platform for testing and developing new bidomain models and coupled ODE solvers in Specific Aim 2.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR008605-18
Application #
8362803
Study Section
Special Emphasis Panel (ZRG1-SBIB-C (40))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
18
Fiscal Year
2011
Total Cost
$29,990
Indirect Cost
Name
University of California San Diego
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Zhang, Qin; Cha, Deukhyun; Bajaj, Chandrajit (2015) Quality Partitioned Meshing of Multi-Material Objects. Procedia Eng 124:187-199

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