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It was found via the mathematical simulation of the effect of fibroblasts on the electrical activity of the sinoatrial node cells that the interaction with fibroblasts through gap junctions increases the oscillation frequency of pacemakers. Under the effect of fibroblasts, the oscillation amplitude of a true pacemaker decreases until the end of the spontaneous activity. The oscillation amplitude of a latent pacemaker decreases considerably less.

We have studied the dynamics of reentry inside the sinoatrial node (SAN). We have found that reentry is unstable at high intercellular conductance. Rotating reentry induces a slow migrating crescent-shaped functional block near the SAN boundary. Abnormal conduction from atrial tissue into the SAN occurs after decay of the reentry. Acetylcholine increases the lifespan of reentry in the SAN.

The initiation and propagation of electrical pulses in the sinoatrial node under normal conditions and after application of acetylcholine have been simulated. It has been found that normally a single or a few leading centers are formed in the tissue. When acetylcholine is applied, a temporary functional block of conduction may appear; the leading center migrates under these conditions.

The duration of the preautomatic pause as a function of sinoatrial node, the type of pacemaker cells, acetylcholine concentration, the duration of high-frequency stimulation, and the conductivity of gap junctions has been studied. It was found that the preautomatic pause in peripheral pacemakers occurs at a higher concentration of acetylcholine as compared with central pacemakers. The dependence of the duration of the preautomatic pause on the gap junction conductivity is a nonlinear one.

While the sinoatrial node (SAN) is structurally heterogeneous, most computer simulations of electrical activity take into account SAN pacemaker cells only. Our aim was to investigate how fibroblasts affect the SAN activity. We simulated the rabbit sinoatrial node accounting for differences between central and peripheral pacemaker cells, and for fibroblast-myocyte electrical coupling. We have observed that only if fibroblast-myocyte coupling is taken into account, (1) action potential is initiated in the central part of the SAN (within 1.2 mm of the center of simulated tissue); otherwise, leading centers are located on the periphery; (2) few (1 to 6) leading centers initiate action potential in the SAN; otherwise, we observed more than 8 leading centers; (3) acetylcholine superfusion results in a shift of leading centers toward the SAN periphery; and (4) sinus pauses up to 1.9 second follow acetylcholine superfusion. We observed negligible effect of fibroblast-myocyte coupling on the period of SAN activation. We conclude that fibroblast-myocyte coupling may explain action potential initiation and propagation from the center of the SAN observed in experimental studies, while atrial load on the peripheral SAN fails to explain this fact.

The effect of fluctuations of the transmembrane potential on the generation of the action potential is studied by simulating the rabbit sinoatrial node (SAN) pacemaker. It is shown that the effect of fluctuations is enhanced with an increase in the concentration of acetylcholine and becomes most pronounced at the border of spontaneous activity loss and after it. When applying and washing off acetylcholine, the hysteretic effect is observed.

With the aid of detailed computer simulations, we have estimated distributions of membrane potential and ionic currents in the core region of a sinoatrial node reentry. We observe reduced amplitudes of the measured quantities in the core; the core sizes for potential and currents did not always coincide. Simulations revealed that acetylcholine, when applied in the vicinity of unstable reentry, attracted the reentry to become the core and to stabilize its rotation. Anatomically detailed simulations of sinoatrial node and surrounding atrial tissue revealed that reentry always rotated around small strips of connective tissue. Acetylcholine superfusion over superior part of the sinoatrial node resulted in a drift of reentry in the cranial direction. Under the latter conditions, reentry may coexist with the pacemaker in the caudal part of the sinoatrial node. Copyright © 2016 John WileySons, Ltd.

Mathematical modeling of the electric activity of pairs of true (central) and latent (peripheral) sinoatrial pacemaker cells coupled through gap junctions revealed that attenuation of coupling conductance increases the beat phase shift; below a critical conductance there is no synchronization. The phase difference also depends on the type of interacting cells, being maximal for a “central”-“peripheral” cell pair.

The effect of periodic stimulation of the vagus nerve on the activity of the central cell of the sinoatrial node has been simulated. The regions of synchronization and desynchronization have been revealed, and the phase shift at different stimulation frequencies has been estimated. The positive chronotropic effect has been shown to occur at some frequencies of stimulation.

With the aid of detailed computer simulations, we have estimated distributions of membrane potential and ionic currents in the core region of a sinoatrial node reentry. We observe reduced amplitudes of the measured quantities in the core; the core sizes for potential and currents did not always coincide. Simulations revealed that acetylcholine, when applied in the vicinity of unstable reentry, attracted the reentry to become the core and to stabilize its rotation. Anatomically detailed simulations of sinoatrial node and surrounding atrial tissue revealed that reentry always rotated around small strips of connective tissue. Acetylcholine superfusion over superior part of the sinoatrial node resulted in a drift of reentry in the cranial direction. Under the latter conditions, reentry may coexist with the pacemaker in the caudal part of the sinoatrial node. Copyright © 2016 John Wiley & Sons, Ltd.

We have simulated 3D propagation of the action potential in the sinoatrial node to study the dynamics of the heart rhythm initiation. We have found that the leading center inside the sinoatrial node is formed by a group of cells, appears spontaneously under normal conditions, and migrates as acetylcholine is applied. The leading center drifts toward the center of the sinoatrial node, if we consider the effect of the surrounding atrial tissue. Abnormal electrical activity, rotating waves of action potential are observed in the sinoatrial node.