Modelling Cardiac Energy Supply during Heart Failure
Lead Research Organisation:
University of Oxford
Department Name: Computer Science
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
Land S
(2014)
Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying ß-adrenergic stimulation in the rat left ventricle.
in American journal of physiology. Heart and circulatory physiology
Augustin CM
(2020)
The impact of wall thickness and curvature on wall stress in patient-specific electromechanical models of the left atrium.
in Biomechanics and modeling in mechanobiology
Land S
(2013)
Beta-adrenergic stimulation maintains cardiac function in Serca2 knockout mice.
in Biophysical journal
Tøndel K
(2014)
Insight into model mechanisms through automatic parameter fitting: a new methodological framework for model development.
in BMC systems biology
Sohal M
(2014)
Delayed Trans-Septal Activation Results in Comparable Hemodynamic Effect of Left Ventricular and Biventricular Endocardial Pacing Insights From Electroanatomical Mapping
in Circulation: Arrhythmia and Electrophysiology
Nordbø O
(2014)
A computational pipeline for quantification of mouse myocardial stiffness parameters.
in Computers in biology and medicine
Shetty AK
(2014)
A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study.
in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
Niederer S
(2011)
Simulating human cardiac electrophysiology on clinical time-scales.
in Frontiers in physiology
Roney C
(2021)
Time-Averaged Wavefront Analysis Demonstrates Preferential Pathways of Atrial Fibrillation, Predicting Pulmonary Vein Isolation Acute Response
in Frontiers in Physiology
Land S
(2015)
Improving the stability of cardiac mechanical simulations.
in IEEE transactions on bio-medical engineering
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 |