Objective
"Understanding of normal and abnormal cardiac excitation and contraction requires the integration of knowledge of myocyte electrophysiology and mechanics with knowledge of dynamic myocardial architecture.
The myocardium is structured as stacked 4-6 cells thick (~100 µm) laminae of myocytes, which have a complex architectural arrangement throughout the cardiac wall and have localised regions of abrupt change in orientation.
Ventricular structure is not an esoteric consideration of form. Along with other functional and structural properties of the myocardium, fibre and laminar architecture determine i) the spread of myocardial activation and ii) the deformation of the wall in contraction. My hypothesis is that: (i) myocardial systolic thickening is enabled by the sliding of sheets over each other, with the laminar architecture serving to limit shear stress; 2) that sheet sliding will have a role in electromechanical feedback which will influence the initiation, propagation and termination of arrhythmias; 3) that myolaminar sliding will be absent in infarct scars, with consequent large strain in the peri-infarct region and that this will have consequences for structural re-organisation, the propagation of activation and arrhythmogenesis in the surrounding myocardium.
These hypotheses will be investigated using ex vivo and in vivo MRI of laminar structure with concurrent electrophysiological (EP) epicardial/endocardial recordings. The study has two phases: (Year 1) preclinical method development in isolated and in situ mouse hearts using high-field strength MRI spectrometers; (Year 2) a translational MRI and EP-mapping in a sheep chronic infarction model. Results will have implications for the fundamental understanding of myocardial architectural dynamics (between systole and diastole) and the role of this in electromechanical feedback, and furthermore, the results will have potential clinical applications."
Fields of science
Topic(s)
Call for proposal
FP7-PEOPLE-2010-IEF
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Funding Scheme
MC-IEF - Intra-European Fellowships (IEF)Coordinator
33404 Talence
France