Mechanism for Amplitude Alternans in Electrocardiograms and the Initiation of Spatiotemporal Chaos

It is widely believed that one major life-threatening transition to chaotic fibrillation occurs via spiral-wave breakup that is preceded by spatiotemporal dispersion of refractoriness due to alternations in the duration of the cardiac action potential (AP). However, recent clinical and experimental evidence suggests that other characteristics of the AP may contribute to, and perhaps drive, this dangerous dynamical instability. To identify the relative roles of AP characteristics, we performed experiments in rabbit hearts under conditions to minimize AP duration dynamics which unmasked pronounced AP amplitude alternans just before the onset of fibrillation. We used a simplified ionic cell model to derive a return map and a stability condition that elucidates a novel underlying mechanism for AP alternans and spiral breakup. We found that inactivation of the sodium current is key to developing amplitude alternans and is directly connected to conduction block and initiation of arrhythmias. Simulations in 2D where AP amplitude alternation led to turbulence confirm our hypothesis.

Figure 1

Action potential alternans. (a) Endocardial microelectrode voltage signals from canine ventricles showing large alternans in APD (32 ms) but no alternans in APA. (b) Optical-mapping voltage signals from a pixel recorded from a rabbit ventricle surface perfused with low-calcium Tyrode’s solution, low flow to simulate ischemia, and paced at a period of 550 ms. Horizontal dotted lines show measurement of DI, solid lines show measurement of APD, and the vertical dashed line APA.

Figure 2

Maps obtained for the numerical cell model. Top: Amplitude restitution curve as a function of the recovery of the $h$ gate (solid line) and period curves (dashed lines) also as a function of $h$ gate for five different periods (320, 340, 360, 380, and 400 ms). Bottom: Cobweb diagram for a period with a stable fixed point (450 ms dashed) and for a period with alternans (368 ms, solid line). Notice that the values for the $h$ gate are bounded between 0 (closed) and 1 (fully open) and the APA alternates between $-8$ and 8 mV.

Figure 3

Pseudo-Electrocardiogram showing pronounced QRS (sharp peaks) alternans from a 1D cable of length 200 cells using the model after pacing four times as in Fig. 1 of the Supplemental Material [11]. Note that since there is little change in APD, $T$-wave alternans is not very pronounced [34].

Figure 4

Top: Optical-mapping voltage signal from one pixel from a rabbit heart with normal Tyrode paced at a fast period showing large APD alternans that is stable. Middle: Similarly, signal from one pixel from rabbit ventricle with low-calcium Tyrode and during APA alternans just before initiation of fibrillation. Bottom: Numerical model’s voltage signal, in 2D, showing APA alternans before conduction block and initiation of arrhythmia.