Biomedical Engineering Reference
In-Depth Information
Fig. 8.12.
The multi-scale cardiac physiome modelling hierarchy from genes to the whole organ-
ism. Parameters used in a model at one scale can often be derived from a more detailed model at a
lower spatial scale
the coronary vasculature, and provides the moving domain for solving the reaction-
diffusion equations that determine the propagating myocardial activation wavefront.
The current that drives the activation processes, however, is generated by membrane
ion channels and these in turn are linked at the sub-cellular level to many biophysi-
cal processes, including calcium transport, myofilament mechanics, metabolic path-
ways, signal transduction pathways, proton and bicarbonate control and gene regu-
latory pathways.
The process of linking multiple biophysical processes across these scales is il-
lustrated in Fig. 8.13. At the organ level the processes are myocardial activation
(Hooks et al., 2002), ventricular wall mechanics (Nash & Hunter, 2001), ventricu-
lar blood flow and heart valve mechanics (Nordsletten et al., 2007), coronary blood
flow (Smith et al., 2002; 2004) and neural control. All of these processes must be
modelled within an integrated framework to capture the substantial interactions, and
all have the same requirement to link down to tissue (LeGrice et al., 1995; 1997)
and cell properties. At the cell level the various cellular processes such as electro-
physiology, calcium transport, myofilament mechanics, metabolic pathways and sig-
nalling networks, also need to be modelled together and these are described using
the CellML framework. In some cases the cellular level models, such as ion channel
electrophysiology, have parameters that are derived from lower level processes, such
as Markov models and these in turn will at some future stage be formed by coarse
