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Biomedical subjects

Roman M Zaritski

Publications and source records attributed to Roman M Zaritski.

4 recordsLinked to original sources

Ionic determinants of functional reentry in a 2-D model of human atrial cells during simulated chronic atrial fibrillation.

Recent studies suggest that atrial fibrillation (AF) is maintained by fibrillatory conduction emanating from a small number of high-frequency reentrant sources (rotors). Our goal was to study the ionic correlates of a rotor during simulated chronic AF conditions. We utilized a two-dimensional (2-D), homogeneous, isotropic sheet (5 x 5 cm(2)) of human atrial cells to create a chronic AF substrate, which was able to sustain a stable rotor (dominant frequency approximately 5.7 Hz, rosette-like tip meander approximately 2.6 cm). Doubling the magnitude of the inward rectifier K(+) current (I(K1)) increased rotor frequency ( approximately 8.4 Hz), and reduced tip meander (approximately 1.7 cm). This rotor stabilization was due to a shortening of the action potential duration and an enhanced cardiac excitability. The latter was caused by a hyperpolarization of the diastolic membrane potential, which increased the availability of the Na(+) current (I(Na)). The rotor was terminated by reducing the maximum conductance (by 90%) of the atrial-specific ultrarapid delayed rectifier K(+) current (I(Kur)), or the transient outward K(+) current (I(to)), but not the fast or slow delayed rectifier K(+) currents (I(Kr)/I(Ks)). Importantly, blockade of I(Kur)/I(to) prolonged the atrial action potential at the plateau, but not at the terminal phase of repolarization, which led to random tip meander and wavebreak, resulting in rotor termination. Altering the rectification profile of I(K1) also slowed down or abolished reentrant activity. In combination, these simulation results provide novel insights into the ionic bases of a sustained rotor in a 2-D chronic AF substrate.

Action Potentials↗

Intermittent self-organization of scroll wave turbulence in three-dimensional excitable media.

We study the asymptotic behavior of scroll wave turbulence in large three-dimensional excitable media modeled by FitzHugh-Nagumo equations. The focus is on the type of turbulence caused by negative tension of scroll wave filaments, which is considered to be one of the mechanisms of cardiac fibrillation. We discovered that the initial increase in turbulence complexity can be followed by intermittent self-organization, when complex filament tangles are replaced by a small number of relatively stable triple filament strands. The intermittency is the result of a competition between the destabilizing effect of negative tension and mutual attraction of filaments with similar orientation.

Computer Simulation↗

Feedback-mediated dynamics in two coupled nephrons.

Previously, we developed a dynamic model for the tubuloglomerular feedback (TGF) system in a single, short-looped nephron of the mammalian kidney. In that model, a semi-linear hyperbolic partial differential equation was used to represent two fundamental processes of solute transport in the nephron's thick ascending limb (TAL): chloride advection by fluid flow along the TAL lumen and transepithelial chloride transport from the lumen to the interstitium. An empirical function and a time delay were used to relate glomerular filtration rate to the chloride concentration at the macula densa of the TAL. Analysis of the model equations indicated that stable limit-cycle oscillations (LCO) in nephron fluid flow and chloride concentration can emerge for sufficiently large feedback gain magnitude and time delay. In this study, the single-nephron model was extended to two nephrons, which were coupled through their filtration rates. Explicit analytical conditions were obtained for bifurcation loci corresponding to two special cases: (1) identical time delays but differing feedback gains, and (2) identical gains but differing delays. Similar to the case of a single nephron, our analysis indicates that stable LCO can emerge in coupled nephrons for sufficiently large gains and delays. However, these LCO may emerge at lower values of the feedback gain, relative to a single (i.e., uncoupled) nephron, or at shorter delays, provided the delays are sufficiently close. These results suggest that, in vivo, if two nephrons are sufficiently similar, then coupling will tend to increase the likelihood of LCO.

Animals↗

Stable spiral structures and their interaction in two-dimensional excitable media.

We study properties and interactions of stable spiral structures in two-dimensional excitable media modeled by equations of FitzHugh-Nagumo type. The presented results rely on the media ability to support unexcited spiral cores. Comparative frequency and dynamics analysis is done for a single spiral, an oppositely charged bound pair, and multiarmed spirals. Higher-frequency structures can attract, repel, or break up structures with lower frequencies. All pairwise reactions are described. A three-armed spiral and a two-armed spiral of opposite charge can form a stable "molecule." A system with high initial vortex concentration evolves according to the described reactions and exhibits three levels of self-organization. In our simulations such evolution led to formation and domination of persistent three-armed spirals.

Algorithms↗