Mechano-Electric Coupling and Arrhythmogenic Current Generation in a Computational Model of Coupled Myocytes

Figures

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  Figure 1. Myocyte stretch protocols. Stretch pattern H (light blue) approximates normal isotonic myocyte shortening with a sinusoidal function. Protocol I (red) is sarcomere isometric contraction. Protocol S (dark blue) simulates late systolic stretch by shifting the sine wave upwards. Protocol P (orange) simulates systolic lengthening such as occurs in acutely ischemic regions.

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  Figure 2. Maximal calcium wave amplitude magnitude and calcium wave velocity in cardiomyocyte simulations at different extracellular calcium concentrations for control (no stretch protocol I), and stretch patterns H, S, and P. (A) The magnitude of the measured maximal calcium wave amplitude increased significantly for all stretch patterns from Cao = 2.0 mM (red data points) to the extracellular calcium concentration at which a calcium wave occurred (blue data points), and 4.2 mM (green data points). Red daggers indicate that no calcium waves occurred in the data set, while red asterisks indicate that the calcium waves triggered additional beats. The related numbers specifies the amount of occurrences within the data set. The data points in light colors specify the first spontaneous event and dark colors are used for the following spontaneous event. (B) The calcium wave velocity increased for all simulations from Cao = 2.0 mM (no waves) to 4.2 mM and from control, to stretch patterns H, to S, and to P. **, *** indicate the statistical significance with p < 0.05 and p < 0.1, respectively.

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  Figure 3. (A) Membrane potential for stretch pattern S of myocyte 3 at Cao = 4.0 mM and Cao = 4.2 mM (from left to right). After one stimulated beat, at Cao = 4.0 mM a calcium-mediated suprathreshold DAD occurred and at Cao = 4.2 mM a calcium-mediated additional beat occurred followed by a calcium wave. (B) Associating calcium wave for the supratheshold DAD, and the additional beat followed by a calcium wave (from left to right) at Cao = 4.0 mM and Cao = 4.2 mM, respectively.

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  Figure 4. APD90 for simulations of myocytes with no (red data points), 1 (blue data points), and 3 coupled fibroblast (green data points) compared with control (no coupled fibroblast) for no contraction and stretch patterns H, S, and P. APD90 was significantly reduced for all simulations of myocytes with coupled myocytes for the different stretch patterns.

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  Figure 5. Maximal calcium wave amplitude and calcium wave velocity for simulations for control (red data points), and myocytes with one (blue data points) and two (green data points) coupled fibroblasts. The data points in light colors specify the first spontaneous event and dark colors are used for the following spontaneous event. (A) For stretch patterns I (control), S, and P the maximal calcium wave amplitude significantly (p < 0.01) decreased the more fibroblasts were coupled to the myocyte. (B) The wave velocity significantly (p < 0.01) decreased for stretch patterns I (control), S, and P for no fibroblast coupled to three coupled fibroblasts. *, **, *** indicate the statistical significance with p < 0.01, p < 0.05, and p < 0.1, respectively.

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  Figure 6. Maximal calcium wave amplitude and calcium wave velocity for simulations of three coupled cardiomyocytes. (A) For all stretch patterns but H (from left to right: control, H, S, and P) the maximal calcium wave amplitude significantly (p < 0.01) decreased the more fibroblasts were coupled to the multi-cellular string (control red data points, 1 coupled fibroblast blue data points, and 3 coupled fibroblasts green data points; the data points in light colors specify the first spontaneous event and dark colors are used for the following spontaneous event). (B) The wave velocity significantly (p < 0.01) decreased for all stretch patterns from no coupled fibroblast to three coupled fibroblasts. *, **, *** indicate the statistical significance with p < 0.01, p < 0.05, and p < 0.1, respectively.

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  Figure 7. (A) Examples of three isolated myocyte APs of the last stimulated beat and the calcium mediated DAD (top), a detailed view of the DAD (bottom left), and the calcium waves in three single cardiomyocytes coupled to three fibroblasts each (bottom right). (B) Example of the APs of three coupled myocytes showing the last stimulated beat and the DAD (top), a detailed view of the DAD (bottom left), and the calcium waves in three coupled cardiomyocytes coupled to three fibroblasts each (bottom right).