Page 117 - YORAM RUDY BOOK FINAL

P. 117
in the electrocardiographic waveform (bottom panel) corresponds to complete repolarization

of the epicardium (top panel), while end of the T-wave reflects complete repolarization of the
mid-myocardium. Thus, the peak-to-end interval of the T-wave provides a measure of repolariza-
tion dispersion (transmural dispersion of repolarization, TDR). These theoretical observations are
consistent with experimental results in the arterially perfused transmural wedge. 248, 250,251,252 The

sequence of repolarization does not follow the endocardial to epicardial sequence of activation; in
fact, epicardial cells repolarize first followed by endocardial cells, and M cells repolarize last. This is
because conduction time between heterogeneous regions (e.g., midmyocardium to epicardium)
is much shorter than intrinsic differences in APD between these regions. As a result, the spatial V
m
gradient (∂V /∂Z in equation 4.16) during repolarization is determined largely by the intrinsic APD
m
heterogeneity (local repolarization properties), rather than by the sequence of activation. During
activation, V gradient is from epicardium (at rest) to mid-myocardium (depolarized). Due to the
m
heterogeneity of intrinsic APD, the V gradient during repolarization is also from epicardium
m
(repolarized) to mid-myocardium (not yet repolarized due to longer APD). Consequently, the QRS
and T-wave are both positive (upright; left bottom panel of Figure 4.4), despite the opposite
polarity of depolarization and repolarization.

In Figure 4.4, middle column, the role of transmural I heterogeneity in determining the
Ks
ECG waveform, and in particular the T-wave morphology, is explored. Comparison to a simulation
where I expression is made homogeneous in the entire fiber, equal to that in endocardial cells
Ks
under control conditions, reveals the effect of I heterogeneity. Under this homogeneous
Ks
condition, the sequence of repolarization follows the sequence of activation with the epicardium
(rather than mid-myocardium) repolarizing last, determining the end of the T-wave and inverting
the V gradient direction relative to the control (physiological) heterogeneous case. The inversion
m
of the V gradient is reflected in the ECG waveform as inversion of the T-wave (middle column,
m
bottom panel).

Another characteristic of ECG waveforms is the J-wave (Osborn wave) . We explore its
253
ionic basis in the right column of Figure 4.4. The J-wave coincides in time with the notch in the

epicardial action potential. This notch is caused by the transient outward (repolarizing) current,
I . To verify that I underlies the ECG J-wave, we eliminated I from the cell model (making its
to
to
to
conductance zero in all cell types). The resulting action potentials and ECG waveform are shown
in gray (control, with physiological I heterogeneous expression is shown in black). In the absence
to
of I , the phase-1 action potential notch and the J-wave disappear, confirming that I is the ionic
to
to
current underlying the J-wave in ECG waveforms.