Biomedical Engineering Reference
In-Depth Information
excitability of cardiac cells because the action potential is heavily influenced by Ca
movements across the membrane, and these in turn are influenced by the mechan-
ical shortening of the cell. Further coupling occurs through stretch-dependent ion
channels (Kohl et al., 2006).
The CellML versions of each of these models are available as follows:
•
Pandit electrophysiology model
www.cellml.org/models/pandit clark giles demir 2001 version07;
•
Hinch calcium dynamics model
www.cellml.org/models/hinch greenstein tanskanen xu winslow 2004 version01;
•
Niederer active contraction model
www.cellml.org/models/niederer hunter smith 2006 version01.
The process of coupling these models in an integrated cell model using the CellML
1.1 import mechanism is shown in Fig. 8.14, where A includes only the Pandit elec-
trophysiology model, B includes the Hinch calcium dynamics and C includes the
Niederer active contraction model. D is the resulting composite model (Terkildsen
et al., 2008). The mathematical components of these separately developed models
are identified with standard biological terms from an ontology such as GO (www.
geneontology.org).
The composite model shown in Fig. 8.14 includes the basic cellular processes
needed to support coupled electro-mechanics in the heart. There are, however, many
other cellular processes that influence these ones and are needed in more compre-
hensive studies of whole heart function. For example, the aerobic metabolic pathway
that controls ATP production has been modelled (Beard, 2005) and is available in
the CellML model repository. The control of key proteins involved in excitatory,
calcium and mechanical function in cardiac cells via
-adrenergic (Saucerman &
McCulloch, 2000; Saucerman et al., 2003), CaM-kinase (Livshitz & Rudy, 2007)
and IP
3
(Cooling et al., 2007) pathways have also been modelled and are available
in CellML. The CellML models for these processes are:
β
•
metabolic pathways
www.cellml.org/models/beard 2005 version01;
•
β
-adrenergic signalling
www.cellml.org/models/saucerman mcculloch 2004 version01;
•
CaM-kinase
www.cellml.org/models/livshitz rudy 2007 version01;
•
IP
3
signalling
www.cellml.org/models/cooling hunter crampin 2007 version01.
Clinical applications of heart modelling
An application of the ML-encoded models and data to clinical diagnostics and treat-
ment planning is illustrated in Fig. 8.15. A 3D stack of DICOM-encoded images
of the patient's heart are loaded into a software environment where they are seg-
