Page 95 - YORAM RUDY BOOK FINAL

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3.4 Propagation in the Wake of a Cardiac Action Potential

We concluded the previous section with a discussion of unidirectional block, an important

ingredient of reentrant arrhythmias, caused by structural inhomogeneities of tissue architecture.
However, structural inhomogeneities are not necessary for the development of unidirectional
block; in fact, it can occur in tissue with completely homogeneous structure and uniform intrinsic
electrical properties. Under such circumstances, the asymmetry of source-sink properties that
underlies directional differences of conduction is introduced by the functional electric asymmetry

of the cardiac action potential itself.

A unidirectional block can develop when local cardiac excitation occurs during the

repolarization phase (tail) of a preceding action potential. 222,223,224 In the heart, this can occur due
to spontaneous premature excitation. There is a critical window during which unidirectional block
can be induced. This “vulnerable window” 222,224,225 can be characterized as time interval in the time
domain (TW), spatial distance in the space domain (SW) and a range of voltages in the voltage
domain (VW). Figure 3.15 is a schematic of the vulnerable window during the repolarization phase

of a propagating action potential (shaded). Outside this window, unidirectional block (or
equivalently, unidirectional conduction) cannot be induced; propagation either fails or succeeds
in both directions when a stimulus is applied to the left or right of the vulnerable window,

respectively (Figure 3.15). In the time domain this translates to too early or too late during the
action potential repolarization phase. For a stimulus in the vulnerable window, the action
potential propagates in the retrograde direction (to the right in Figure 3.15) but blocks in the
antegrade direction (left in Figure 3.15). Because in the retrograde direction the tissue is progres-
sively more recovered from refractoriness as the distance increases, propagation is incremental in

this direction. Conversely, in the antegrade direction the membrane is progressively less excitable
with distance and propagation in this direction is decremental.

Figure 3.16 shows a simulation of propagation induced by a premature stimulus in the
vulnerable window, in the wake of a propagating action potential. In the retrograde direction, the
action potential propagated a distance of 40 cells before reaching the region of fully excitable
membrane. The conduction velocity was only 19.5 cm/sec along the first 10 cells. As the distance
increased, the velocity gradually increased, reaching 38.2 cm/sec along cells 30 to 40. In the

antegrade direction, propagation gradually diminished as membrane excitability decreased in
this direction. The action potential gradually decreased in amplitude and its velocity slowed
gradually as well (17.5 cm/sec in the first 5 cells; 9.7 cm/sec in the next 5 cells). The graded nature of

electrical excitability for an action potential induced in the vulnerable window is clearly depicted
in Figure 3.16. In the retrograde direction, sodium channel availability (g ) recovers slowly from
Na
curve 1 to curve 5, reflecting the time course of recovery of the sodium channel inactivation gate,
h (the activation gate, m, is practically fully recovered and does not determine the behavior of g ).
Na
In the antegrade direction, there is a sharp decrease in g from curve 3 to curve 4. This decre-
Na
mental behavior reflects the sharp decrease in the activation parameter, m.