The goal of this Core is to create whole-heart models of normal and failing rabbit hearts from Diffusion Tensor Magnetic Resonance Imaging (DTMRI), to serve as a platform for whole-heart model testing of the hypotheses developed by the Projects. Our basic strategy is to take the phenomena being studied in the Projects, and place them into anatomically accurate whole-heart models to ask the critical question: how do these molecular, cellular, and tissue-level effects play out in the anatomically complex failing heart? In order to create these models, we have developed new mathematical methods for creating structural models from DTMRI. The review endorsed the idea that whole heart modeling is a useful strategy. It also endorsed our new methods for creating high-resolution detailed geometric models of particular hearts, using DTMRI raw data. Due to the new restrictions on proposal length, we are omitting a lot of the detailed technical presentation of these methods from the previous proposal. The review also supported our third aim, which is to provide quantitative data analysis tools for the Projects. ("... quantitative data analysis, which is highly important for drawing the correct conclusions from the experimental data.... The ideas related to the interpretation of optical recordings of transmembrane voltage activity are interesting and important) The review of the links to the Projects commented: "...Links to 1 [and] Link to 3 is strong, 2 and 4 less so." In response, we have strengthened the interactions with Projects 2 and 4.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Special Emphasis Panel (ZHL1-PPG-S)
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University of California Los Angeles
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Qu, Zhilin; Weiss, James N (2015) Mechanisms of ventricular arrhythmias: from molecular fluctuations to electrical turbulence. Annu Rev Physiol 77:29-55
Nivala, Michael; Song, Zhen; Weiss, James N et al. (2015) T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling. J Mol Cell Cardiol 79:32-41
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Hoang, Allen; Shen, Changyu; Zheng, James et al. (2014) Utilization rates of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death: a 2012 calculation for a midwestern health referral region. Heart Rhythm 11:849-55
Pezhouman, Arash; Madahian, Sepideh; Stepanyan, Hayk et al. (2014) Selective inhibition of late sodium current suppresses ventricular tachycardia and fibrillation in intact rat hearts. Heart Rhythm 11:492-501
Hellyer, Jessica; George Akingba, A; Rhee, Kyoung-Suk et al. (2014) Autonomic nerve activity and blood pressure in ambulatory dogs. Heart Rhythm 11:307-13
Yu, Chih-Chieh; Ai, Tomohiko; Weiss, James N et al. (2014) Apamin does not inhibit human cardiac Na+ current, L-type Ca2+ current or other major K+ currents. PLoS One 9:e96691
Chen, Peng-Sheng; Chen, Lan S; Fishbein, Michael C et al. (2014) Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circ Res 114:1500-15

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