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The making of the virtual heart 137

These detailed cell models can be used to study the development in
time of processes like myocardial ischaemia (a reduction in coronary blood
flow that causes under-supply of oxygen to the cardiac muscle), or effects
of genetic mutations on cellular electrophysiology. They allow to predict
the outcome of changes in the cell’s environment, and may even be used
to assess drug actions.

8.4.3 Organ models
Clearly, cardiac function may not be addressed exclusively on the basis of
describing the working mechanisms of single cells. Both normal and dis-
turbed heart rhythms are based on a spreading wave of electrical excita-
tion, the meaningful investigation of which requires conduction pathways
of at least hundreds if not thousands of cells in length.
These may be produced by grouping together multiple cell models to
form virtual tissue segments, or even the whole organ. The validity of such
multi-cellular constructs crucially depends on whether or not they take
into account the heart’s fine architecture, as cardiac structure and function
are tightly interrelated.
Modern representations of the virtual heart, therefore, describe struc-
tural aspects like fibre orientation in cardiac muscle, together with the dis-
tribution of various cell types, active and passive electrical and mechanical
properties, as well as the coupling between cells. This then allows accurate
reproduction of the spread of the electrical wave, subsequent contraction
of the heart, and effects on blood pressure, coronary perfusion, etc. It is
important to point out, here, that all these parameters are closely interre-
lated, and changes in any one of them influence the behaviour of all others.
This makes for an exceedingly complex system.
The example in Figure 8.2 illustrates a combination of ‘only’ two sub-
systems to study the effects of cardiac contraction on coronary tree archi-
tecture and function. Models like this allow one to determine changes in
coronary blood pressure during the cardiac cycle of contraction and relax-
ation. Like in the real heart, the coronary tree moves with the cardiac
tissue, into which it is embedded, and the pressure inside the vessels
changes with the external compression by the contracting muscle. This
external pressure is calculated and shown with the deforming coronary
vessel tree in Figure 8.2. Thus, current electro-mechanical models of ven-
tricular anatomy and function allow one to describe coronary perfusion
during the cardiac cycle. By linking this to the models of cell metabolism