Working Group 2: Cardiac and Skeletal Muscle Physiology

Working Group Lead: Dan Beard,

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.

Working Group 2 Participants

Current Discussion

March, 2010

We are discussing Directions and Initiatives for WG2.


Resent Presentation

Friday March 13, 2009 3-4pm EST - Dan Beard, Medical College of Wisconsin

Audio: 877-601-3553, passcode: 31207

Adobe Connect:

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

Model Repository

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 [1] 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.


Relevant Papers

  • (September 2008) From mitochondrial ion channels to arrhythmias in the heart: computational techniques to bridge the spatio-temporal scales.
Plank G, Zhou L, Greenstein JL, Cortassa S, Winslow RL, O'Rourke B, Trayanova NA
Philos Transact A Math Phys Eng Sci. 2008 Sep 28;366(1879):3381-409 Pubmed link
ABSTRACT - Computer simulations of electrical behaviour in the whole ventricles have become commonplace during the last few years. The goals of this article are (i) to review the techniques that are currently employed to model cardiac electrical activity in the heart, discussing the strengths and weaknesses of the various approaches, and (ii) to implement a novel modelling approach, based on physiological reasoning, that lifts some of the restrictions imposed by current state-of-the-art ionic models... 


  • (November 2008) Systems biology of vascular endothelial growth factors.
Mac Gabhann F, Popel AS.
Microcirculation. 2008 Nov;15(8):715-38 Pubmed link
ABSTRACT - Several cytokine families have roles in the development, maintenance, and remodeling of the microcirculation. Of these, the vascular endothelial growth factor (VEGF) family is one of the best studied and one of the most complex. Five VEGF ligand genes and five cell-surface receptor genes are known in the human, and each of these may be transcribed as multiple splice isoforms to generate an extensive family of proteins, many of which are subject to further proteolytic processing. Using the VEGF family as an example, we describe the current knowledge of growth-factor expression, processing, and transport in vivo....


  • (November 2008) A molecular signaling model of platelet phosphoinositide and calcium regulation during homeostasis and P2Y activation
Purvis JE, Chatterjee MS, Brass LF, Diamond SL.
Blood. 2008 Nov 15;112(10):4069-79 Pubmed link
ABSTRACT - To quantify how various molecular mechanisms are integrated to maintain platelet homeostasis and allow responsiveness to adenosine diphosphate (ADP), we developed a computational model of the human platelet. Existing kinetic information for 77 reactions, 132 fixed kinetic rate constants, and 70 species was combined with electrochemical calculations, measurements of platelet ultrastructure, novel experimental results, and published single-cell data...
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