Multi-scale Approaches to Mechanical Contraction and Electrical Wave Conduction in A 3D Model of Human Atria during Fibrillation

Lead Research Organisation: Lancaster University
Department Name: Engineering

Abstract

One of the "grand challenges" of integrative biology is to predict the behaviour of an organ that emerges from integrated actions of molecules, ions, cells and tissues operating at multi-physical scales. Cardiac electro-physiology is sufficiently well established for developing a predictive model for the heart. However, successful simulations of cardiac dynamics requires not only well-validated mathematical model of cardiac electro-mechanics and anatomy, but also stable and efficient numerical algorithms for solving these models that are at multiple physical scales, highly complex and non-linear. The aim of this project is to tackle these challenges for human sinoatrial node - atria (SAN-atria) (the upper chambers of the heart), malfunction of that causes morbidity and mortality. We propose to develop a new generation 3D anatomical model of the SAN-atria with coupled electrical and mechanical dynamics, and a new family of numerically stable and efficient algorithms based on discrete element methods. Using the model, we shall quantify the functional impact of pharmacological interventions on atrial electrical and mechanic dynamics. The output of this project will be a family of novel computer models of human SAN-atria and efficient numerical algorithms for cardiac electro-mechanical modelling. The developed model and numerical solvers will be distributed for public access through our local research websites and international depository tools (www.cellML.org and www.fieldML.org).
 
Description Both single-cell and tissue models were developed for the electrical and mechanical behaviour of the human atria. The single-cell model is able to accurately recreate the active force development, cell shortening, action potential & intracellular current densities of a human atrial myocyt, and the tissue model allows us to account for the discrete arrangement of individual cells and fibre direction. Its numerical efficacy permits a significant portion of tissue to be studied, which is able to sustain, eg. contraction and spiral waves. Using our model, we have found that Mechanical-electrical feedback (MEF) slows down cardiac conduction, destabilises re-entrant spiral waves, accelerates excitation rate of spiral waves, increases the average spiral wave tip meandering speed, and increases the size of meandering area. It is also shown that atrial fibrillation induced electrical remodelling (AFER) drastically reduces the mechanical activity of tissue, owing to the lessened cell shortening resulting from reduced calcium transient.
Exploitation Route Through open access publications, software developer and collaborations with local hospitals. Please see the Key Findings of EPSRC Grant:
Sectors Digital/Communication/Information Technologies (including Software),Education,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description We are working with medical professionals and software company (ITASCA) to promote the use of our discrete model.Please see the Impact Summary of EPSRC Grant EP/J00958X/1
Sector Education,Healthcare
Impact Types Societal

 
Title Research Tools 
Description use multiscale modelling strategy to model fibrillation of human atrium 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact The immediate benefit will be for the rapidly growing international community of Computational Biology and Computational Materials that use reaction-diffusion PDEs and micro scale discrete elements. In general, development of stable and efficient methods for the PDE problem of electro-mechanic cardiac models with complex 3D boundaries and discrete cell arrangement is becoming ever more intensive research area for mathematicians and software developers. The ideas and practical solutions stemming from our project will be of further beneficiary to that community. The indirect benefit will be via research outputs of this project. Further long term potential beneficiaries will be outside academia, such as pharmaceutical and biomedical engineering industrials, and hence eventually patients and general public. These benefits would be through the newly developed tools and algorithms that can address more efficiently the mechanisms of cardiac arrhythmias and drug safety test. 
 
Description New collaboration (Industry) 
Organisation Blackpool Victoria Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution New collaboration has been established with Victoria Blackpool Hospital through this project
Collaborator Contribution participate in progress meetings and provide technical advices
Impact This is a multidisciplinary research requiring expertise from Cardiac electrophysiology, mathematics, material science and computational modelling.
Start Year 2014
 
Description Research collaboration (University) -eHeart 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution As the PI at Lancaster contributing to the project leading by Manchester
Collaborator Contribution Leading the project involving Lancaster and Leeds
Impact All the publications were and will be co-authored. This is a multidisciplinary research requiring expertise from Cardiac electrophysiology, mathematics, material science and computational modelling.
Start Year 2013
 
Description Research collaboration (industry)-eHeart 
Organisation ITS United Kingdom
Country United Kingdom 
Sector Private 
PI Contribution PI at Lancaster on DEM modelling of human atrium
Collaborator Contribution Technical support on using software and providing necessary plug-in
Impact The project is multidisciplinary involving Cardiac electrophysiology , mathematics, material and computational modelling. paper have been published and we are working on new proposals.
Start Year 2013
 
Description Engagement (e-Heart) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presentations made to Medical Doctors from Regional hospital to promote the research and request inputs.
Year(s) Of Engagement Activity 2013,2014