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4.3 The Ionic Current Basis of Electrocardiographic Waveforms

In this section, we provide examples of how the field-theory formalism presented in the

previous section can be used to relate ECG waveforms to ionic processes at the cellular level. The
electrocardiogram has been used for over 100 years to detect and diagnose rhythm disorders
of the heart, yet its interpretation remains mostly empirical. With the major recent advances in
our understanding of the molecular and cellular basis of cardiac arrhythmias, establishing a link
between cellular processes and the ECG is needed for specific diagnosis of electrophysiological

disorders.

During sinus-rhythm excitation of the heart (the normal excitation sequence), broad planar

wave fronts are formed by the Purkinje network that propagate from endocardium to epicardium
across the ventricular wall . Propagation of this planar wave front can be simulated as conduction
1
in a 1-dimensional fiber model. 247 Such model also represents action potential propagation in the
arterially perfused transmural wedge preparation, used in experimental studies of ECG wave-
forms. 248

The model used here represents a 1.65cm long transmural segment, composed of 165 LRd
model cells interconnected through gap junctions. Transmural heterogeneities of ion channel

expression are incorporated to represent the three cell types: endocardial, mid-myocardial (M),
and epicardial cells. The cell types differ in expression levels of I (lowest in M cells) and I
Ks
to
(highest in epicardial cells; zero in endocardial cells) as previously described. 133,247,249 The fiber is
paced endocardially, to generate endocardium to epicardium action potential propagation. Once
V is computed along the fiber, equations (4.16) or (4.17) of the previous section can be used to
m
compute the extracellular potential ϕ . In the following example, ϕ computed at an “electrode”
0
0
site 2.0cm away from the epicardium along the fiber axis is presented as the ECG wave-
form (“pseudo-ECG”). Pseudo-ECGs have been used extensively in many experimental
preparations and in computer models. They have proven extremely useful in relating

ECG waveforms to the action potential and its underlying ionic processes.

The ECG Reflection of Heterogeneities in Ion Channel Expression

In Figure 4.4, the relationship between the ECG waveform and the transmural
heterogeneity of I and I is established. In normal myocardium, I expression is lower in the
to
Ks
Ks
mid-myocardium (M cells) than in either the endocardium or epicardium. I expression increases
to
monotonically from endocardium to epicardium. This is the control situation simulated in the left
column of Figure 4.4. The small I in M cells prolongs their action potential duration (APD)
Ks
relative to that of epicardial or endocardial cells (APD =187ms; APD =148ms). The outward I
epi
to
M
current produces a notch in the action potential during phase-1 repolarization in epicardial and M
cells (arrows) but not in endocardial cells where I is absent . Importantly, the peak of the T-wave
to