Working Group Lead: Dan Beard, email@example.com
Goals and Objectives: The main objective of this working group is to share strategies, databases, and programs to facilitate collaborations leading to the development of integrated multi-scale models of skeletal/cardiac muscle physiology.
Given the small size of the working group and the relatively close topics of investigation by each project, our focus centers mainly around developing collaborations among WG members and projects.
We are discussing Directions and Initiatives for WG2.
Friday March 13, 2009 3-4pm EST - Dan Beard, Medical College of Wisconsin
Audio: 877-601-3553, passcode: 31207
Adobe Connect: https://webmeeting.nih.gov/r93134274/
Experimentally observed phenomena on cardiac energetics in heart failure emerge from simulations of cardiac metabolism
The failing heart is hypothesized to suffer from energy supply inadequate for supporting normal cardiac function. We analyzed data from a canine left ventricular hypertrophy (LVH) model to determine how the energy state evolves due to changes in key metabolic pools. Our findings-confirmed by in vivo 31P-magnetic resonance spectroscopy (31P-MRS)-indicate that the transition between the clinically observed early compensatory phase and heart failure and the critical point at which the transition occurs are emergent properties of cardiac energy metabolism. Specifically, analysis reveals a phenomenon in which low and moderate reductions in metabolite pools have no major negative impact on oxidative capacity while reductions beyond a critical tipping point lead to a severely compromised energy state. The transition point corresponds to reductions in the total adenine nucleotide pool (TAN) of approximately 30%, corresponding to the reduction observed in humans in heart failure [Circ Res 95:135-145]. At given values of TAN and the total exchangeable phosphate pool (TEP) during hypertrophic remodeling, the creatine pool (CRtot) attains a value that is associated with optimal ATP hydrolysis potential. Thus, both increases and decreases to the creatine pool are predicted to result in diminished energetic state unless accompanied by appropriate simultaneous changes in the other pools.
Powerpoint presentation: Media: Beard13March2009.ppt
Related article: Media: BeardSISB.pdf
Past Discussions and Working Group 2 Reports
Univ.Washington 2007 Media:AnnReport07.pdf
NSR Physiome Project Model Wiki, University of Washington (Bassingthwaighte)
NSR Physiome Project Modeling Resource Page, University of Washington (Bassingthwaighte)
Understanding the Regulation of Respiration in vivo as a Multiscale Complex System
Pierre Carlier - Institute of Myology, Paris, FRANCE and Marco E. Cabrera - Case Western Reserve University, USA
Central and Peripheral Factors Contributing to the Impaired Oxidative Metabolism in Microgravity: Experimental and theoretical approach.
Bruno Grassi - Universita degli Studi di Udine, ITALY and Nicola Lai - Case Western Reserve University, USA; Marco E. Cabrera - Case Western Reserve University, USA
Multiscale predictive models of insulin resistance and interventions.
Jinwook Seo and Eric Hoffman - Children's National Medical Center; and Marco E. Cabrera - Rainbow Babies and Children's Hospital, CWRU.
Multiscale Computational Modeling of Oxygen Transport and Metabolism.
Ranjan Dash and Dan Beard - Medical College of Wisconsin; and Nicola Lai and Marco E. Cabrera - Case Western Reserve University
Multiscale Model of Cardiac Metabolism during Ischemia
Ranjan Dash - Medical College of Wisconsin; William Stanley - University of Maryland, Baltimore, MD; and Marco E. Cabrera - Case Western Reserve University
Multiscale Model of Muscle Metabolism in Vascular Disease
Bruce Gladden - Auburn University, AL; Kevin McCully - University of Georgia, Athens, GA; and Nicola Lai and Marco E. Cabrera - Case Western Reserve University, OH
The NSR Physiome Project will be holding two five-day simulation and modeling courses on "Cardiovascular and Respiratory Systems Modeling: From Cell to Organ" on June 14-18 2010, and August 23-27, 2010 at the University of Washington, Seattle. These courses are for graduate students, investigators, and clinicians wanting to gain experience in mathematical modeling for the analysis of physiological and pharamcological data. Please see the  webpage for more information.
The course fee is $400/person. There are a small number of scholarships and travel stipends available. Please register using our online form
Courses are funded by NIH/NHLBI 1 T15 HL008516.
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