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Details of Grant 

EPSRC Reference: EP/F043929/1
Title: Modelling Cardiac Energy Supply during Heart Failure
Principal Investigator: Niederer, Dr SA
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Mayo Clinic and Foundation (Rochester) Medical College of Wisconsin University of Auckland
Department: Computer Science
Organisation: University of Oxford
Scheme: Postdoc Research Fellowship
Starts: 01 April 2009 Ends: 01 September 2010 Value (£): 252,717
EPSRC Research Topic Classifications:
Medical science & disease
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
10 Mar 2008 LSI Postdoctoral Fellowships Interview Panel 2008 Announced
11 Feb 2008 LSI Postdoctoral Research Fellowships 2008 InvitedForInterview
Summary on Grant Application Form
Heart failure is a lethal syndrome representing a common 'final pathway' for sufferers of a multitude of cardiac and respiratory diseases. 1 in 5 people will suffer from heart failure during their life time and once diagnosed ~40% of patients die within one year. Heart failure is caused by the heart's inability to perfuse the organs of the body with blood. The energy starvation hypothesis is a new model of heart failure and proposes that the reduced supply of energy is a fundamental cause of heart failure. The energy starvation hypothesis is the result of genetic studies and new experimental methodologies and provides a unifying mechanism to explain the development of cardiac contractile failure, yet the significance of compromised energy supply is debated. This project will investigate the importance of the energy starvation hypothesis by analysing the extent to which decreases in energy supply during heart failure compromise heart function. The cardiac energy supply chain (CESC) spans from the organ to the sub cellular scale. Energy supply decreases during heart failure due to the compromise of independent compounding links of the CESC at the organ, tissue and cellular scale. At the organ scale, blood flow through the arteries supplying blood to the heart decreases. At the tissue scale, oxygen and metabolite flux from the capillaries to the cells is reduced. At the cellular scale, the conversion of oxygen and metabolites to high energy molecules and the transport of these to the points of utilization are inhibited. I propose to investigate the energy supply to heart cells in the failing heart by developing a series of coupled models representing the cellular scale (metabolism, electrical activity, biochemical, contraction), tissue scale (movement of oxygen and metabolites, capillary circulation) and organ scale (blood supply to the heart, mechanics, electrical activation) components of the CESC. Changing model parameters and geometries will then allow the CESC during heart failure to be simulated. The model will be systematically validated against experimental results at each stage in model development. The final integrated multi-scale model will be used to test the energy starvation hypothesis by quantifying how the individual and integrated changes to the CESC during heart failure affect whole heart function.In order to build these models, we will use sophisticated image processing techniques to build an accurate 3D geometrical representation of the heart, arteries supplying blood to the heart and capillary network from high resolution datasets. Advanced numerical methods will be used to formulate mathematical equations for the transduction of energy within the heart. Cutting edge experimental procedures will provide key information on changes in cellular, tissue and organ structure and function during heart failure. Such combinations of mathematical modelling techniques and experimental investigations are vital for elucidating the mechanisms underlying the causes and progression of heart failure and may ultimately lead to improved treatment and prevention.
Key Findings
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Organisation Website: http://www.ox.ac.uk