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  Spatially Discordant Alternans in Cardiac TissueRole of Calcium Cycling

  Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu and Alain Karma

  Circulation Research. 2006;99:520-527, originally published August 31, 2006

  https://doi.org/10.1161/01.RES.0000240542.03986.e7

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  Spatially Discordant Alternans in Cardiac Tissue

  Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu, Alain Karma

  Circulation Research September 2006, 99 (5) 520-527; DOI: https://doi.org/10.1161/01.RES.0000240542.03986.e7

  

  By Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu and Alain Karma

  Figure 1. A, Illustration of the Cai cycling machinery and ionic currents implemented in the ionic model. B, Illustration of graded release coupling....Show More

  Figure 1. A, Illustration of the Cai cycling machinery and ionic currents implemented in the ionic model. B, Illustration of graded release coupling. The peak of the Cai transient at a given beat (lower trace) depends on the DI at the previous beat (upper trace). The DI influences the magnitude of the Ca current and hence the amount of Ca release at the next beat. Here, the peak of the Ca transient on the next beat, denoted by Ca1 and Ca2, corresponds to DI1 and DI2 respectively. C, Illustration of positive and negative Cai→Vm coupling. Positive (negative) coupling refers to the case when a large Cai transient at a given beat tends to prolong (shorten) the APD of that beat. D, Illustration of electromechanically in-phase and out-of-phase alternans during steady-state pacing.Show Less
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  Spatially Discordant Alternans in Cardiac Tissue

  Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu, Alain Karma

  Circulation Research September 2006, 99 (5) 520-527; DOI: https://doi.org/10.1161/01.RES.0000240542.03986.e7

  

  By Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu and Alain Karma

  Figure 2. Alternans dynamics during the dynamic pacing protocol. A, Steady-state normalized amplitude of APD (ΔAPD) and Cai transient (ΔCai) alternans...Show More

  Figure 2. Alternans dynamics during the dynamic pacing protocol. A, Steady-state normalized amplitude of APD (ΔAPD) and Cai transient (ΔCai) alternans as a function of PCL for an isolated cardiac cell paced using the dynamic pacing protocol. Here, the amplitude of alternans is normalized to the maximum value. The cell model is adjusted so that the Cai→Vm coupling is positive. Here, alternans amplitude is measured by subtracting the APD and peak Cai at the 50th and 49th beats at the given PCL. The onset of alternans is denoted by the vertical dashed line. B, Same simulation as in A using cell model parameters with negative Cai→Vm coupling. C, Amplitude of alternans within two electrotonically paced cardiac cells. Here, the cell model used is the same as in A. D, Same simulation as in C, using the same model parameters as in B. Notice that the onset of alternans (vertical green line) occurs at an earlier PCL than in the isolated cell (vertical black line).Show Less
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  Spatially Discordant Alternans in Cardiac Tissue

  Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu, Alain Karma

  Circulation Research September 2006, 99 (5) 520-527; DOI: https://doi.org/10.1161/01.RES.0000240542.03986.e7

  

  By Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu and Alain Karma

  Figure 3. Distribution of Cai transient and APD alternans amplitude along a cable of cells with the same model parameters as in Figure 2A (positive Ca...Show More

  Figure 3. Distribution of Cai transient and APD alternans amplitude along a cable of cells with the same model parameters as in Figure 2A (positive Cai→Vm coupling). During the dynamic pacing protocol alternans amplitude was measured for each cell by computing ΔCai and ΔAPD from the 49th and 50th beats at PCL=400 ms (A), PCL=310 ms (B), and PCL=280 ms (C). D through F, Same simulation using the model parameters used in Figure 2B (negative Cai→Vm coupling) for PCL=400, 358, 340 ms. In all graphs, ΔCai and ΔAPD are normalized to the maximum value observed during the dynamic pacing protocol.Show Less
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  Spatially Discordant Alternans in Cardiac Tissue

  Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu, Alain Karma

  Circulation Research September 2006, 99 (5) 520-527; DOI: https://doi.org/10.1161/01.RES.0000240542.03986.e7

  

  By Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu and Alain Karma

  Figure 4. CV during discordant alternans. A, CV computed for the 49th (dashed line) and 50th (solid line) paced beats at PCL=280 ms, during the same s...Show More

  Figure 4. CV during discordant alternans. A, CV computed for the 49th (dashed line) and 50th (solid line) paced beats at PCL=280 ms, during the same simulation shown in Figure 3C. B, CV restitution curve for the ionic model parameters used in Figure 3C. The vertical dashed lines marks the maximum range of DI engaged along the cable during the 50th beat. C, CV measured along the cable for the 2 beats used to compute Figure 3F. D, CV restitution curve for the model parameters used in Figure 3F. Again, the dashed lines denote the range of DI engaged during the discordant alternans pattern shown in Figure 3F.Show Less
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  Spatially Discordant Alternans in Cardiac Tissue

  Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu, Alain Karma

  Circulation Research September 2006, 99 (5) 520-527; DOI: https://doi.org/10.1161/01.RES.0000240542.03986.e7

  

  By Daisuke Sato, Yohannes Shiferaw, Alan Garfinkel, James N. Weiss, Zhilin Qu and Alain Karma

  Figure 5. Schematic illustration of the desynchronization/synchronization mechanism when single-cell alternans are electromechanically in phase and ou...Show More

  Figure 5. Schematic illustration of the desynchronization/synchronization mechanism when single-cell alternans are electromechanically in phase and out of phase. A, Vm and Cai vs time for neighboring cells 1 and 2 with negative Cai→Vm coupling. The cells are uncoupled before time t1, after which they are coupled electrotonically. The red line denotes the time evolution after electrotonic coupling at time t1. B, Same illustration as A with positive Cai→Vm coupling.Show Less
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  From Pulsus to PulselessThe Saga of Cardiac Alternans

  James N. Weiss, Alain Karma, Yohannes Shiferaw, Peng-Sheng Chen, Alan Garfinkel and Zhilin Qu

  Circulation Research. 2006;98:1244-1253, originally published May 25, 2006

  https://doi.org/10.1161/01.RES.0000224540.97431.f0

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  From Pulsus to Pulseless

  James N. Weiss, Alain Karma, Yohannes Shiferaw, Peng-Sheng Chen, Alan Garfinkel, Zhilin Qu

  Circulation Research May 2006, 98 (10) 1244-1253; DOI: https://doi.org/10.1161/01.RES.0000224540.97431.f0

  

  By James N. Weiss, Alain Karma, Yohannes Shiferaw, Peng-Sheng Chen, Alan Garfinkel and Zhilin Qu

  Figure 1. Spatially concordant (A) and discordant (B) APD alternans in simulated 2D cardiac tissue. A, Top traces show that simulated action potential...Show More

  Figure 1. Spatially concordant (A) and discordant (B) APD alternans in simulated 2D cardiac tissue. A, Top traces show that simulated action potentials from sites a and b both alternate in a long-short pattern during pacing at 220-ms CL. Second panel shows that the spatial APD distribution is either long (blue) or short (red for each beat). Third panel shows that the APD dispersion (gray scale) for either long or short beats is minimal. Bottom panel shows simulated electrocardiogram (ECG), with T wave alternans. B, Top traces show that at a pacing CL of 180 ms, simulated action potentials from site a now alternate short-long, whereas at the same time, action potentials from site b alternate long–short. Second panel shows the spatial APD distribution, with a nodal line (white) with no APD alternation separating the out-of-phase top and bottom regions. Third panel shows that the APD dispersion is markedly enhanced, with the steepest gradient (black) located at the nodal line. Bottom panel shows simulated ECG, with both T wave and QRS alternans (attributable to engagement of CV restitution), as observed experimentally.10 Simulations used a modified Luo–Rudy action potential model described previously.11Show Less
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  From Pulsus to Pulseless

  James N. Weiss, Alain Karma, Yohannes Shiferaw, Peng-Sheng Chen, Alan Garfinkel, Zhilin Qu

  Circulation Research May 2006, 98 (10) 1244-1253; DOI: https://doi.org/10.1161/01.RES.0000224540.97431.f0

  

  By James N. Weiss, Alain Karma, Yohannes Shiferaw, Peng-Sheng Chen, Alan Garfinkel and Zhilin Qu

  Figure 2. Mechanism of initiation of re-entry by a premature ectopic beat during spatially discordant alternans. A premature ectopic beat (asterisk) o...Show More

  Figure 2. Mechanism of initiation of re-entry by a premature ectopic beat during spatially discordant alternans. A premature ectopic beat (asterisk) occurring in the region of short APD blocks (black line) as it propagates across the nodal line into the region with long APD. Meanwhile, the ectopic beat successfully propagates laterally, waiting for the long APD region to repolarize and then re-enters the blocked region to initiate figure-eight re-entry.Show Less
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  From Pulsus to Pulseless

  James N. Weiss, Alain Karma, Yohannes Shiferaw, Peng-Sheng Chen, Alan Garfinkel, Zhilin Qu

  Circulation Research May 2006, 98 (10) 1244-1253; DOI: https://doi.org/10.1161/01.RES.0000224540.97431.f0

  

  By James N. Weiss, Alain Karma, Yohannes Shiferaw, Peng-Sheng Chen, Alan Garfinkel and Zhilin Qu

  Figure 3. Cobweb diagram of APD alternans arising from steep APD restitution slope, after Nolasco and Dahlen.15 Blue line shows the APD restitution cu...Show More

  Figure 3. Cobweb diagram of APD alternans arising from steep APD restitution slope, after Nolasco and Dahlen.15 Blue line shows the APD restitution curve, and red line shows the CL=APD+DI line. The top graph illustrates the effects of a perturbation, which shortens DI (asterisk), displacing the system from its unstable equilibrium point (solid black circle at the intersection of the two lines), resulting in persistent APD alternans, as shown in the bottom trace. See text for details.Show Less

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