TY - JOUR
T1 - From mitochondrial ion channels to arrhythmias in the heart
T2 - Computational techniques to bridge the spatio-temporal scales
AU - Plank, Gernot
AU - Zhou, Lufang
AU - Greenstein, Joseph L.
AU - Cortassa, Sonia Carmen
AU - Winslow, Raimond L.
AU - O'Rourke, Brian
AU - Trayanova, Natalia A.
PY - 2008/9/28
Y1 - 2008/9/28
N2 - Computer simulations of electrical behaviour in the whole ventricles have become commonplace during the last few years. The goals of this article are (i) to review the techniques that are currently employed to model cardiac electrical activity in the heart, discussing the strengths and weaknesses of the various approaches, and (ii) to implement a novel modelling approach, based on physiological reasoning, that lifts some of the restrictions imposed by current state-of-the-art ionic models. To illustrate the latter approach, the present study uses a recently developed ionic model of the ventricular myocyte that incorporates an excitation-contraction coupling and mitochondrial energetics model. A paradigm to bridge the vastly disparate spatial and temporal scales, from subcellular processes to the entire organ, and from sub-microseconds to minutes, is presented. Achieving sufficient computational efficiency is the key to success in the quest to develop multiscale realistic models that are expected to lead to better understanding of the mechanisms of arrhythmia induction following failure at the organelle level, and ultimately to the development of novel therapeutic applications.
AB - Computer simulations of electrical behaviour in the whole ventricles have become commonplace during the last few years. The goals of this article are (i) to review the techniques that are currently employed to model cardiac electrical activity in the heart, discussing the strengths and weaknesses of the various approaches, and (ii) to implement a novel modelling approach, based on physiological reasoning, that lifts some of the restrictions imposed by current state-of-the-art ionic models. To illustrate the latter approach, the present study uses a recently developed ionic model of the ventricular myocyte that incorporates an excitation-contraction coupling and mitochondrial energetics model. A paradigm to bridge the vastly disparate spatial and temporal scales, from subcellular processes to the entire organ, and from sub-microseconds to minutes, is presented. Achieving sufficient computational efficiency is the key to success in the quest to develop multiscale realistic models that are expected to lead to better understanding of the mechanisms of arrhythmia induction following failure at the organelle level, and ultimately to the development of novel therapeutic applications.
KW - Bidomain
KW - Cardiac electrical activity
KW - Monodomain
KW - Multiscale modelling
KW - Ordinary differential equation integration
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U2 - 10.1098/rsta.2008.0112
DO - 10.1098/rsta.2008.0112
M3 - Article
C2 - 18603526
AN - SCOPUS:49549084409
SN - 1364-503X
VL - 366
SP - 3381
EP - 3409
JO - Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
JF - Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
IS - 1879
ER -