Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties

Figures

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  Figure 1. (A) The schematics of global analysis. Spatiotemporally processed signals recorded from multiple points on a line, showing staggered action potentials upstrokes consistent with wavefront propagation. (B) Same signals as A shifted to align the upstrokes. (C) The first principle component ( W1) displays alternans. (D) Spectrogram of C, showing a 1:2 peak of alternans. The second principle component ( W2) displays more pronounced alternans larger than C (E). Spectrogram of E, shows a prominent 1:2 peak of alternans (F). The bar in A depicts 200 ms.

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  Figure 2. The schematic of composite restitution-curve generation. An exponential curve fits a set of (DI, APD) data points for one pixel. (A) The 95% confidence-interval curves are also shown. (B) The restitution curves for all the pixels in a region of interest (say, with Period-2 on the local analysis) are calculated (only 100 curves are shown here). (C) Monte Carlo sampling is performed to generate a composite restitution curve (the thick central line) and the confidence interval (shown as a continuum). APD, action potential duration; DI, diastolic interval.

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  Figure 3. Comparison of baseline and pre-VF spectrograms using global analysis. The lower spectrograms are the baseline (stimulation cycle length of 500 ms except for H4 at 800 ms) and the upper spectrograms are obtained just before VF induction. (A and B) H1, H2 exhibit prominent 1:4 peaks, while no discernable 1:4 peak is seen for (D) H6. H4 has a ∼0.18 peak, corresponding to mainly (C) Period-6 activity. The baseline signals are multiplied by 0.1 to offset the signals for better visualization.

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  Figure 4. The pacing frequency dependence of 1:2 and 1:4 peaks. In both panels, the 1:2 peak (the classic APD alternans) starts when the cycle length decreases to ∼400 ms. On the other hand, the 1:4 peak only rises above the baseline once the cycle length decreases to 300–350 ms. Also, note the different scaling of the 1:4 peak compared with the 1:2 peak, which is 2–3 orders of magnitude smaller than the 1:2 peak. These results significantly reduce the chance that the observed 1:4 peaks are processing artefacts and point to their dynamical origin.

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  Figure 5. Examples of signals with different periodicities. Representative pixel-level optical-mapping signals with (A and B) Period-2, (C and D) Period-4, (E and F) Period-6, (G and H) Period-8, and (I and J) higher-order/chaotic are shown. Note the intermittency of Period-8. APD, action potential duration.

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  Figure 6. The distribution of higher-order areas. (A) In H1, there are multiple Period-4 areas in a sea of classic alternans. (B) H2 shows both 1:4 and 1:6 areas. (C) H5 has large areas of Period-6 without significant Period-4. (D) The main feature of H6 is a large area of Period-8 without significant 1:2 or 1:4 regions . The background images represent anatomy. The pixels are colored based on their periodicitiy according to the colorbar on the right. Atr, atrial; El, pacing electrode; Ven, ventricles.

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  Figure 7. The relative frequency of different periodicities. Each histogram shows the relative proportions of pixels with a given period (in the range of 1–8) for each of the six hearts.

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  Figure 8. The electrophysiological characteristics of areas with different periodicities. The top row (A and B) shows the overlapped restitution curves for two hearts. The curves depict regions of Periods 1 and 2 (low) and areas of Periods 3–8 (high). The restitution curves are so similar that it is difficult to separate the two curves. (C–H) The electrophysiological properties (restitution-curve parameters and conduction velocity) between each heart’s low and high periods regions. Restitution curves are parameterized by APD∞, DI0, and τ (see the Methods section). The ratio of conduction velocity at fast pacing rates (the last three recordings before fibrillation) to the conduction velocity during slow pacing (remaining recordings) is denoted ρ.