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University of Auckland

Country: New Zealand
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42 Projects, page 1 of 9
  • Funder: UKRI Project Code: EP/P008690/1
    Funder Contribution: 12,814 GBP
    Partners: University of Auckland, University of Liverpool

    Despite over a century's study, the mechanisms of cardiac arrhythmias are poorly understood. Even modern experimental methods do not provide sufficient temporal and spacial resolution to trace down fine details of fibrillation development in samples of cardiac tissue, not to mention the heart in vivo. Advances in human genetics provide information on the impact of certain genes on cellular activity, but do not explain the resultant mechanisms by which fibrillation arises. Thus, for some genetic cardiac diseases, the first presenting symptom is death. Combination of mathematical modelling and the latest realistic computer simulations of electrical activity in the heart have much advanced our understanding of heart fibrillation and sudden cardiac death, and the impact of in-silico modelling, or indeed in-silico "testing", is expected to increase significantly as we approach the ultimate goal of the whole-heart modelling. Biophysically and anatomically realistic simulation of cardiac action potential propagation through the heart is computationally expensive due to the huge number of equations per cell and the vast spacial and temporal scales required. Therefore any insights that can be obtained through generic mathematical model analysis is very valuable, as it tends to reveal generic mechanisms, unlike direct computer simulations, which provide answers valid only for a specific choice of parameters and initial conditions and depend on the computer model accuracy. Note that despite of the decades of steady progress, computer models still have qualitative rather than quantitative predictive power on the macroscopic scale, e.g. where whole heart or a whole chamber of the heart are concerned. Our recent progress in asymptotic analysis of dissipative vortices dynamics has revealed a new phenomenon of the vortices interaction with sharp variations of thickness in excitable layer. Such interaction of cardiac re-entry with sharp anatomical features, as e.g. pectinate muscles and terminal crest in atria, can cause considerable displacement of established localisation of re-entry compared to where it was first localised. The asymptotic theory prediction of the vortices drift caused by interaction with sharp thickness variations in a layer has been confirmed in experiments with Belousov-Zhabotinski reaction, and verified in computer simulations with a variety of cell excitation models, from extremely simplified "conceptual" models to realistic ionic kinetics models, and for tissue geometries from artificial idealised geometries to a realistic anatomy of human atria. A better underestanding of this phenomenon may have significant implications in clinics, say for chosing an individual ablation strategy for treatment of atrial fibrillation. Validation of the identified new phenomenon has so far been done only on a single model of human atrium, and understanding of to what extent the effect is universal requires extensive testing on a wide variety of cardiac MRI anatomy models, before experimental testing and clinical implications can be considered. The aim of the proposed project is to visit the Auckland Bioengineering Institute (ABI), New Zealand, which is an international leader in the heart and cardiovascular system research that combines instrumentation development, experimental measurements and modelling. ABI cardiovascular magnetic resonance (CMR) imaging group obtains most detail models of heart geometry and tissue microstructure. This visit will forge a closer collaboration than it is feasible from a distance, and provide a possibility of exhaustive testing of the new phenomenon in the most up-to-date anatomically and biophysically realistic models. An extra benefit will be provided by the applicant's participation in Cardiac Physiome Workshop (23 August 2016, Seoul, Korea), which will be a unique opportunity to discuss our recent findings and future directions of research with the world leaders in the field.

  • Funder: EC Project Code: 617060
    Partners: University of Auckland, UM
  • Funder: EC Project Code: 339993
  • Funder: UKRI Project Code: BB/S020616/1
    Funder Contribution: 30,612 GBP
    Partners: The Riddet Institute, University of Auckland, IFR

    Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

  • Funder: UKRI Project Code: EP/F043929/2
    Funder Contribution: 140,221 GBP
    Partners: University of Auckland, Mayo Clinic and Foundation, MCW, KCL

    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.