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The making of the virtual heart 143

relaxing between beats, which impedes the filling of the cardiac chambers
and prevents effective pumping function.
Might this be reversed by pharmacological interventions? Figure 8.3(c)
illustrates the application of a (virtual) drug that specifically activates one
type of the potassium channels in the heart (the so-called ATP-modulated
potassium channel, whose activity is increased in the model from 0 to
0.0002). This intervention leads to termination of the dangerous depola-
risations at the cellular level and allows the whole heart to regain a stable
resting state (compare last frames of the sequences in Figure 8.3(b) and (c).
Thus, while the pattern of impulse conduction in the heart has not entirely
normalised, the development of fatal re-entry is terminated.
Thus, the virtual heart may be used to simulate cardiac pathologies,
their effect on the ECG, and the consequences of drug administration. It
can be seen that drug discovery and assessment will be among the first
fields where in silico technologies could reform research and development
in a whole industry.

8.4.5 Summary: The virtual heart
Analytical models of the heart are a reality. They are based on detailed
descriptions of cardiac tissue architecture and anatomy, including the cor-
onary vasculature. In silico cardiac tissues possess realistic passive
mechanical properties, and both electrical and mechanical activity can be
simulated with high accuracy. Descriptions of key components of cellular
metabolism have been introduced, as have models of drug–receptor
interactions.
The individual modules of the in situ heart can be coupled together to
compute a whole sequence from ventricular pressure development, coro-
nary perfusion, tissue supply of metabolites, cell energy consumption, and
electrophysiology, to contractile activity and ventricular pressure develop-
ment in the subsequent beat. The ‘starting point’ (here chosen as ventric-
ular pressure development) can be freely selected, and drug effects on the
system can be simulated. ‘Inserted’ into a virtual torso, these models allow
one to compute the spread of excitation, its cellular basis, and the conse-
quences for an ECG under normal and pathological conditions.
Ongoing work is devoted to the accurate description of the origin and
spread of excitation from the natural pacemaker to the rest of the heart.
Computations of ventricular pressure development are being extended
to account for blood flow dynamics in adjacent blood vessels. The thorax