A compact multi-functional model of the rabbit atrioventricular node with dual pathways

Figures

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  FIGURE 1. (A) Conduction system of the mammalian heart. SN—sinus node, AVN—atrioventricular node, RA and LA—right and left atria, PB—penetrating bundle, HB—His bundle, TV—tricuspid valve, RV and LV—right and left ventricles. (B) Anatomic drawing of the rabbit atrioventricular node and surrounding tissues with excitation wave latency (from (de Carvalho et al., 1959)). CT—crista terminalis, CS—coronary sinus, TZ—transitional zone, and INE—inferior nodal extension. The numbers in milliseconds are given with respect to the sinus node pacemaker. The fast and slow pathways are indicated by red and blue lines, respectively.

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  FIGURE 2. Schematic representation of the rabbit cardiac conduction model with dual pathways. SN - sinus node cell, PS1–PS3 - peripheral sinus node cells, AM1–AM3 - right atrial muscle cells, FP1–FP8 - fast pathway cells, SP1–SP10 - slow pathway cells, PB - penetrating bundle cell, HB1–HB6 - His bundle cells. Arrows Antero and Retro denote the points for anterograde and retrograde S1S2 stimuli application, arrow AF indicates the point of stimuli application for random pacing (atrial fibrillation) and regular pacing (atrial flutter), and AM* is an additional intermediate atrial muscle cell. The gray-shaded cells indicate primary and subsidiary pacemaker cells.

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  FIGURE 3. Distributions of refractory period for uncoupled model cells, coupling coefficient d, and coefficient of coupling asymmetry α. Opaque and filled circles denote excitable and pacemaking cells, respectively. For d and α plots, the data in SP with indexes 6.5 and 15.5 correspond to “verical” coupling between the rows of the AVN model.

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  FIGURE 4. Primary and subsidiary pacemaking. Here and after top scheme illustrates propagation conduction sequences of interacting fast (FP, red arrows) and slow (SP, blue arrows) pathways. Top panel: the laddergram (Lewis ladder diagram) with the exact timing of each model cell excitation. Smaller circles denote quiescent excitable model cells, and larger circles - natural pacemaker cells. Red and blue traces correspond to the propagation through the FP and SP, respectively. The trace color in the HB part corresponds to the leading pathway. Dark red arrowhead markers on the right side and the adjacent lines denote the points of latency time measurements. Middle panel: the sequence of action potentials passing through the FP between the SN and HB. Bottom panel: the sequence of action potentials passing through the SP between the SN and HB. Action potentials in red correspond to the latency time measurement points, and in black color - to the pacemaking cells. Time scale is common for all three panels. (A) Rabbit’s normal sinus rhythm of 166 bpm (361 ms interval). The numbers on the traces indicate excitation wave latency with respect to the SN in milliseconds. (B) In the case of a silent…

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  FIGURE 5. Atrial pacing in the control case with S1S2 interval of 140 ms and 130 ms. (A) At 140 ms interval, the excitation wave arrives via the FP and SP to the PB almost simultaneously with a slight advance of the FP. (B) The conduction in the FP is stopped due to a functional conduction block. In the top panel, arrowhead markers indicate points of stimulation. Upper (between the markers) and lower numbers correspond to the S1S2 and H1H2 intervals, respectively. Short stimulation impulses are shown at the top of the middle panel.

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  FIGURE 6. (A) Atrial pacing in the control case with S1S2 interval of 110 ms. Perpetual SP–FP AVNRT. (B) Atrial pacing for the control case with S1S2 interval of 94 ms. Full nodal conduction block.

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  FIGURE 7. SP and FP ablations. (A) Atrial pacing with S1S2 interval of 110 ms after SP ablation. See Figure 6A for comparison. (B) Atrial pacing with S1S2 interval of 140 ms after FP ablation. See Figure 5A for comparison.

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  FIGURE 8. Retrograde AVN conduction, HB pacing with 175 ms S1S2 interval. (A) Control case. (B) After FP ablation. (C) After SP ablation. Upper and lower numbers correspond to A1A2 and S1S2 (H1H2) intervals. Short stimulation impulses are shown at the bottom of the middle panel.

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  FIGURE 9. Comparison of experimental (Reid et al., 2003) (left panels) and simulated (right panels) anterograde and retrograde recovery curves in the control case and after FP and SP ablations. (A) Experimental recovery curves in the control case and after FP ablation and simulated recovery curves. (B) Experimental recovery curves in the control case and after SP ablation and simulated recovery curves. Dashed lines correspond to the simulated retrograde conduction in the control case without coupling asymmetry.

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  FIGURE 10. Comparison of experimental (left panels) and simulated (right panels) conduction curves. (A) Experimental (Tadros and Billette, 2012) and simulated AVN refractory, His-atrial, and recovery curves. (B) Experimental (Xu et al., 2006) and simulated refractory curves before and after SP ablation. The simulated control refractory curves (H1H2) in the right panels are the same.

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  FIGURE 11. Filtering of atrial rhythm during atrial fibrillation stimulated by random impulse sequence in 75–125 ms range applied to AM* model cell. The short stimulation impulses and resulting AM* cell action potentials are shown in the top part of the middle panel.

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  FIGURE 12. Impact of ablation on AVN filtering function. (A) Laddergrams of atrial fibrillation stimulated by the same random impulse sequence as in Figure 11 after SP ablation (top panel) and after FP ablation (bottom panel). (B) Distribution of consecutive HH intervals for intact AVN and after ablations. Random atrial pacing in the 75–125 ms range was applied for 350 s. Control case (left panel), after SP ablation (middle panel), and after FP ablation (right panel). Mean HH intervals and HB rates for each case are shown at the bottom.