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Edward J Vigmond

Publications and source records attributed to Edward J Vigmond.

10 recordsLinked to original sources
PubMed2006

Inward rectifying potassium channels facilitate cell-to-cell communication in hamster retractor muscle feed arteries.

This study examined whether inward rectifying K+ (KIR) channels facilitate cell-to-cell communication along skeletal muscle resistance arteries. With the use of feed arteries from the hamster retractor muscle, experiments examined whether KIR channels were functionally expressed and whether channel blockade attenuated the conduction of acetylcholine-induced vasodilation, an index of cell-to-cell communication. Consistent with KIR channel expression, this study observed the following: 1) a sustained Ba2+-sensitive, K+-induced dilation in preconstricted arteries; 2) a Ba2+-sensitive inwardly rectifying K+ current in arterial smooth muscle cells; and 3) KIR2.1 and KIR2.2 expression in the smooth muscle layer of these arteries. It was subsequently shown that the discrete application of acetylcholine elicits a vasodilation that conducts with limited decay along the feed artery wall. In the presence of 100 microM Ba2+, the local and conducted response to acetylcholine was attenuated, a finding consistent with a role for KIR in facilitating cell-to-cell communication. A computational model of vascular communication accurately predicted these observations. Control experiments revealed that in contrast to Ba2+, ATP-sensitive- and large-conductance Ca2+ activated-K+ channel inhibitors had no effect on the local or conducted vasodilatory response to acetylcholine. We conclude that smooth muscle KIR channels play a key role in facilitating cell-to-cell communication along skeletal muscle resistance arteries. We attribute this facilitation to the intrinsic property of negative slope conductance, a biophysical feature common to KIR2.1- and 2.2-containing channels, which enables them to increase their activity as a cell hyperpolarizes.

Acetylcholine↗
PubMed2005

Defining electrical communication in skeletal muscle resistance arteries: a computational approach.

Vascular cells communicate electrically to coordinate their activity and control tissue blood flow. To foster a quantitative understanding of this fundamental process, we developed a computational model that was structured to mimic a skeletal muscle resistance artery. Each endothelial cell and smooth muscle cell in our virtual artery was treated as the electrical equivalent of a capacitor coupled in parallel with a non-linear resistor representing ionic conductance; intercellular gap junctions were represented by ohmic resistors. Simulations revealed that the vessel wall is not a syncytium in which electrical stimuli spread equally to all constitutive cells. Indeed, electrical signals spread in a differential manner among and between endothelial cells and smooth muscle cells according to the initial stimulus. The predictions of our model agree with physiological data from the feed artery of the hamster retractor muscle. Cell orientation and coupling resistance were the principal factors that enable electrical signals to spread differentially along and between the two cell types. Our computational observations also illustrated how gap junctional coupling enables the vessel wall to filter and transform transient electrical events into sustained voltage responses. Functionally, differential electrical communication would permit discrete regions of smooth muscle activity to locally regulate blood flow and the endothelium to coordinate regional changes in tissue perfusion.

Animals↗
PubMed2005

Mechanisms of atrial fibrillation termination by pure sodium channel blockade in an ionically-realistic mathematical model.

The mechanisms by which Na+-channel blocking antiarrhythmic drugs terminate atrial fibrillation (AF) remain unclear. Classical "leading-circle" theory suggests that Na+-channel blockade should, if anything, promote re-entry. We used an ionically-based mathematical model of vagotonic AF to evaluate the effects of applying pure Na+-current (I(Na)) inhibition during sustained arrhythmia. Under control conditions, AF was maintained by 1 or 2 dominant spiral waves, with fibrillatory propagation at critical levels of action potential duration (APD) dispersion. I(Na) inhibition terminated AF increasingly with increasing block, terminating all AF at 65% block. During 1:1 conduction, I(Na) inhibition reduced APD (by 13% at 4 Hz and 60% block), conduction velocity (by 37%), and re-entry wavelength (by 24%). During AF, I(Na) inhibition increased the size of primary rotors and reduced re-entry rate (eg, dominant frequency decreased by 33% at 60% I(Na) inhibition) while decreasing generation of secondary wavelets by wavebreak. Three mechanisms contributed to I(Na) block-induced AF termination in the model: (1) enlargement of the center of rotation beyond the capacity of the computational substrate; (2) decreased anchoring to functional obstacles, increasing meander and extinction at boundaries; and (3) reduction in the number of secondary wavelets that could provide new primary rotors. Optical mapping in isolated sheep hearts confirmed that tetrodotoxin dose-dependently terminates AF while producing effects qualitatively like those of I(Na) inhibition in the mathematical model. We conclude that pure INa inhibition terminates AF, producing activation changes consistent with previous clinical and experimental observations. These results provide insights into previously enigmatic mechanisms of class I antiarrhythmic drug-induced AF termination. The full text of this article is available online at http://circres.ahajournals.org

Algorithms↗
PubMed2005

Defibrillation depends on conductivity fluctuations and the degree of disorganization in reentry patterns.

UNLABELLED: Defibrillation depends on conductivity and disorganization. INTRODUCTION: Cardiac fibrillation is the deterioration of the heart's normally well-organized activity into one or more meandering spiral waves, which subsequently break up into many meandering wave fronts. Delivery of an electric shock (defibrillation) is the only effective way of restoring the normal rhythm. This study focuses on examining whether higher degrees of disorganization requires higher shock strengths to defibrillate and whether microscopic conductivity fluctuations favor shock success. METHODS AND RESULTS: We developed a three-dimensional computer bidomain model of a block of cardiac tissue with straight fibers immersed in a conductive bath. The membrane behavior was described by the Courtemanche human atrial action potential model incorporating electroporation and an acetylcholine- (ACh) dependent potassium current. Intracellular conductivities were varied stochastically around nominal values with variations of up to 50%. A single rotor reentry was initiated and, by adjusting the spatial ACh variation, the level of organization could be controlled. The single rotor could be stabilized or spiral wave breakup could be provoked leading to fibrillatory-like activity. For each level of organization, multiple shock timings and strengths were applied to compute the probability of shock success as a function of shock strength. CONCLUSIONS: Our results suggest that the level of the small-scale conductivity fluctuations is a very important factor in defibrillation. A higher variation significantly lowers the required shock strength. Further, we demonstrated that success also heavily depends on the level of organization of the fibrillatory episode. In general, higher levels of disorganization require higher shock strengths to defibrillate.

Acetylcholine↗
PubMed2004

The effect of vagally induced dispersion of action potential duration on atrial arrhythmogenesis.

OBJECTIVE: The purpose of this study is to ascertain the effects of spatially variable ACh distributions on arrhythmogenesis in a morphologically realistic computer model of canine atria. BACKGROUND: Vagal stimulation releases acetylcholine (ACh), which causes a dose-dependent reduction in action potential duration (APD) in the atria. Due to the nonuniform distribution of nerve endings, APD dispersion may result, which has been shown to play a role in the breakup of activity. METHODS: Reentry was initiated in a computationally efficient, morphologically realistic computer model of the atria. Discrete regions corresponding to ACh release sites, referred to as islands, were assigned shortened APDs in an ACh-dependent fashion. Island APD was varied as well as the basal APD. The window of vulnerability for ectopic beat-induction of sustained reentry was determined for both left atrial(LA) and right atrial (RA) stimulation. The resulting reentries were categorized based on type and location. RESULTS: 1) Atrial geometry severely restricts the formation of reentrant circuits. 2) Wave fractionation only occurred for large differences between island and basal APD. 3) Small ACh concentration differences produced stable figure-of-8 reentrant patterns. 4) Large islands displayed more wave breakup but could sometimes anchor reentries. CONCLUSIONS: Large APD gradients produced by ACh heterogeneity can lead to a breakdown of organized activity.

Acetylcholine↗
PubMed2004

Parallel multigrid preconditioner for the cardiac bidomain model.

The bidomain equations are widely used for the simulation of electrical activity in cardiac tissue but are computationally expensive, limiting the size of the problem which can be modeled. The purpose of this study is to determine more efficient ways to solve the elliptic portion of the bidomain equations, the most computationally expensive part of the computation. Specifically, we assessed the performance of a parallel multigrid (MG) preconditioner for a conjugate gradient solver. We employed an operator splitting technique, dividing the computation in a parabolic equation, an elliptical equation, and a nonlinear system of ordinary differential equations at each time step. The elliptic equation was solved by the preconditioned conjugate gradient method, and the traditional block incomplete LU parallel preconditioner (ILU) was compared to MG. Execution time was minimized for each preconditioner by adjusting the fill-in factor for ILU, and by choosing the optimal number of levels for MG. The parallel implementation was based on the PETSc library and we report results for up to 16 nodes on a distributed cluster, for two and three dimensional simulations. A direct solver was also available to compare results for single processor runs. MG was found to solve the system in one third of the time required by ILU but required about 40% more memory. Thus, MG offered an attractive tradeoff between memory usage and speed, since its performance lay between those of the classic iterative methods (slow and low memory consumption) and direct methods (fast and high memory consumption). Results suggest the MG preconditioner is well suited for quickly and accurately solving the bidomain equations.

Algorithms↗
PubMed2003

Computational tools for modeling electrical activity in cardiac tissue.

Computer models offer many attractive benefits. However, the modeling of cardiac tissue is computationally expensive due to several physical constraints which result in fine spatiotemporal discretization over large spatiotemporal regions. Our laboratory has been actively trying to develop new techniques to make large scale cardiac simulations tractable over the past 15 years. This paper describes the latest modeling software that our group has developed, called Carp (Cardiac arrhythmias research package). It is designed to run in both shared memory and clustered computing environments. Carp aims to be modular and flexible by following a plug-in framework. This allows the latest models and most efficient solvers to be incorporated as well as enabling run-time selection of techniques. Performance results are given for a large-scale simulation which utilized a comprehensive membrane ionic current description.

Action Potentials↗
PubMed2002

Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties.

Classical concepts of atrial fibrillation (AF) have been rooted in Moe's multiple-wavelet hypothesis and simple cellular-automaton computer model. Recent experimental work has raised questions about the multiple-wavelet mechanism, suggesting a discrete "driver region" underlying AF. We reexplored the theoretical basis for AF with a 2-dimensional computer model of a 5x10-cm sheet of atrial cells with realistic ionic and coupling properties. Vagal actions were formulated based on patch-clamp studies of acetylcholine (ACh) effects. In control, a single extrastimulus resulted in a highly meandering unstable spiral wave. Simulated electrograms showed fibrillatory activity, with a dominant frequency (DF, 6.5 Hz) that correlated with the mean rate. Uniform ACh reduced core meander of the spiral wave by approximately 70% (as measured by the standard deviation of spiral-wave tip position) and accelerated the DF to 17.0 Hz. Simulated vagally induced refractoriness heterogeneity caused wavefront breakup as accelerated reentrant activity in regions of short refractoriness impinged on regions unable to respond in a 1:1 fashion because of longer refractoriness. In 7 simulations spanning the range of conditions giving sustained AF, 5 were maintained by single dominant spiral waves. On average, 3.0+/-1.3 wavelets were present (range, 1 to 7). Most wavelets were short-lived and did not contribute to AF maintenance. In contrast to predictions of the multiple-wavelet hypothesis, but in agreement with recent experimental evidence, our model indicates that AF can result from relatively stable primary spiral-wave generators and is significantly organized. Our results suggest that vagal AF may arise from ACh-induced stabilization of the primary spiral-wave generator and disorganization of the heterogeneous tissue response. The full text of this article is available at http://www.circresaha.org.

Acetylcholine↗
PubMed2002

Computational techniques for solving the bidomain equations in three dimensions.

The bidomain equations are the most complete description of cardiac electrical activity. Their numerical solution is, however, computationally demanding, especially in three dimensions, because of the fine temporal and spatial sampling required. This paper methodically examines computational performance when solving the bidomain equations. Several techniques to speed up this computation are examined in this paper. The first step was to recast the equations into a parabolic part and an elliptic part. The parabolic part was solved by either the finite-element method (FEM) or the interconnected cable model model (ICCM). The elliptic equation was solved by FEM on a coarser grid than the parabolic problem and at a reduced frequency. The performance of iterative and direct linear equation system solvers was analyzed as well as the scalability and parallelizability of each method. Results indicate that the ICCM was twice as fast as the FEM for solving the parabolic problem, but when the total problem was considered, this resulted in only a 20% decrease in computation time. The elliptic problem could be solved on a coarser grid at one-quarter of the frequency at which the parabolic problem was solved and still maintain reasonable accuracy. Direct methods were faster than iterative methods by at least 50% when a good estimate of the extracellular potential was required. Parallelization over four processors was efficient only when the model comprised at least 500,000 nodes. Thus, it was possible to speed up solution of the bidomain equations by an order of magnitude with a slight decrease in accuracy.

Algorithms↗