Modelling Cardiac Energy Supply during Heart Failure

Lead Research Organisation: King's College London
Department Name: Imaging & Biomedical Engineering

Abstract

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.

Publications

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De Oliveira B (2016) Computational models of doxorubicin mitochondria cardiotoxicity in Journal of Pharmacological and Toxicological Methods

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Lamata P (2014) Images as drivers of progress in cardiac computational modelling. in Progress in biophysics and molecular biology

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Land S (2018) Influence of atrial contraction dynamics on cardiac function. in International journal for numerical methods in biomedical engineering

Related Projects

Project Reference Relationship Related To Start End Award Value
EP/F043929/1 01/04/2009 01/09/2010 £252,717
EP/F043929/2 Transfer EP/F043929/1 01/09/2010 30/09/2012 £140,222
 
Description Code verification standard included in FDA recommendation paper on verifying models
Geographic Reach North America 
Policy Influence Type Citation in other policy documents
URL http://onlinelibrary.wiley.com/doi/10.1002/cnm.2615/abstract;jsessionid=E893A41DF0E1EAAEC7B9C02E20E0...
 
Description Conference Presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I presented my results at an international conference. there were on the order of 100 people in the session

Attendee was recruited into my lab.
Year(s) Of Engagement Activity 2013
URL http://cardiacphysiome.org/
 
Description Glasgow Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited seminar talk

improved awareness of my work
Year(s) Of Engagement Activity 2013
 
Description Leeds Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact invited seminar series

Improved awareness of my work
Year(s) Of Engagement Activity 2012
 
Description School visits 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Schools
Results and Impact I have promoted the field of biomedical engineering at schools in London, Surrey and Manchester. Audience size ranges from 15-40 pupils.

We continue to analyse feedback data to see if promotion of bio medical engineering leads to an increase in enrollments but this has yet to materialize.
Year(s) Of Engagement Activity 2012,2013
 
Description Sheffield Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar series a university of Shefield

none
Year(s) Of Engagement Activity 2013
 
Description University of Oxford Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited speaker Oxford seminar series

Improved awareness of my work
Year(s) Of Engagement Activity 2012