Design of an Interactive Simulation Environment for Arrays of Cardiac Cells.

The electrical activity of cardiac cells is complex and their collective action difficult to visualize. Understanding what is happening, overall and cell by cell, requires detailed simulation. Here the design of such a simulation is defined by a list of required tasks.

Robust Prediction Of Treatment Times In Concurrent Patient Care.

Outpatient centers comprised of many concurrent clinics increasingly see higher patient volumes. In these centers, decisions to improve clinic flow must account for the high degree of interdependence when critical personnel or equipment is shared between clinics. Discrete event simulation models have provided clinical decision support, but rarely address high-volume clinics with shared resources.

A structural framework for interpretation of four-electrode microimpedance spectra in cardiac tissue.

Renewed interest in the four-electrode method for identification of passive electrical properties in cardiac tissue has been sparked by a recognition that measurements made with sensors in close proximity are frequency dependent. Therefore, resolution of four-electrode microimpedance spectra (4EMS) may provide an opportunity for routine identification of passive electrical properties for the interstitial and intracellular compartments using only interstitial access. The present study documents a structural framework in which the tissue resistivity (ρt) and reactivity (xt) that comprise spectra are computed using interstitial and intracellular microimpedance distributions that account for differences in compartment size, anisotropic electrical properties in each compartment and electrode separations.

Bioelectricity-AQA, one of the first MOOC courses in engineering.

Bioelectricity-AQA was one of the first massively open online courses in engineering, having been given the first time via Coursera starting in September, 2012. This report provides some detail on its background, presentation, enrollment, and lessons learned.

Sensor spacing affects the tissue impedance spectra of rabbit ventricular epicardium.

This study was designed to test the hypothesis that a complex composite impedance spectra develops when stimulation and recording of cardiac muscle with sufficiently fine spatial resolution in a four-electrode configuration is used. With traditional (millimeter scale) separations, the ratio between the recorded interstitial central potential difference and total supplied interstitial current is constant at all frequencies. This occurs because the fraction of supplied current that redistributes to the intracellular compartment depends on effective membrane resistance between electrodes, which is low, to a much greater extent than effective membrane capacitance.

A new approach for resolution of complex tissue impedance spectra in hearts.

This study was designed to test the feasibility of using sinusoidal approximation in combination with a new instrumentation approach to resolve complex impedance (uCI) spectra from heart preparations. To assess that feasibility, we applied stimuli in the 10-4000 Hz range and recorded potential differences (uPDs) in a four-electrode configuration that allowed identification of probe constants (Kp) during calibration that were in turn used to measure total tissue resistivity ρt from rabbit ventricular epicardium. Simultaneous acquisition of a signal proportional to the supplied current (Vstim) with uPD allowed identification of the V- I ratio needed for ρt measurement, as well as the phase shift from Vstim to uPD needed for uCI spectra resolution.

A biophysical model for cardiac microimpedance measurements.

Alterations to cell-to-cell electrical conductance and to the structural arrangement of the collagen network in cardiac tissue are recognized contributors to arrhythmia development, yet no present method allows direct in vivo measurements of these conductances at their true microscopic scale. The present report documents such a plan, which involves interstitial multisite stimulation at a subcellular to cellular size scale, and verifies the performance of the method through biophysical modeling. Although elements of the plan have been analyzed previously, their performance as a whole is considered here in a comprehensive way.

Bayesian quantitative electrophysiology and its multiple applications in bioengineering.

Bayesian interpretation of observations began in the early 1700s, and scientific electrophysiology began in the late 1700s. For two centuries these two fields developed mostly separately. In part that was because quantitative Bayesian interpretation, in principle a powerful method of relating measurements to their underlying sources, often required too many steps to be feasible with hand calculation in real applications.

Bayesian analysis of fiber impedance measurements.

The resistivities of microscale components of excitable tissue include the longitudinal intracellular and interstitial resistivities and the membrane resistivity. Measurements of these tissue micro impedances have rarely been obtained, mainly because of the lack of a satisfactory measurement system. Here we evaluate a possible strategy for obtaining such measurements, and begin with a simulation.

Multisite interstitial stimulation for cardiac micro-impedance measurements.

On theoretical grounds, interstitial current injected and removed using electrodes in close proximity does not cross the membrane, while equilibration of intracellular and interstitial potentials occurs distant from electrodes widely separated. Multisite interstitial stimulation should therefore give rise to interstitial potential differences recorded centrally that depend on intracellular and interstitial micro-impedances, allowing independent measurement. We tested the feasibility of completing such measurements using simulations of multisite stimulation with fine and wide spacing in models that included Luo-Rudy dynamic (LRd) membrane equations.

Electric fields around and within single cells during electroporation-a model study.

One of the key issues in electric field-mediated molecular delivery into cells is how the intracellular field is altered by electroporation. Therefore, we simulated the electric field in both the extracellular and intracellular domains of spherical cells during electroporation. The electroporated membrane was modeled macroscopically by assuming that its electric resistivity was smaller than that of the intact membrane.

Mechanism of origin of conduction disturbances in aging human atrial bundles: experimental and model study.

Background: Aging is associated with a significant increase in atrial tachyarrhythmias, especially atrial fibrillation. A macroscopic repolarization gradient created artificially by a stimulus at one site before a premature stimulus from a second site is widely considered to be part of the experimental protocol necessary for the initiation of such arrhythmias in the laboratory. How such gradients occur naturally in aging atrial tissue is unknown.

A computer model of electrical stimulation of peripheral nerves in regional anesthesia.

Background: Nerve stimulation for regional anesthesia can be modeled mathematically. The authors present a mathematical framework to model the underlying electrophysiology, the development of software to implement that framework, and examples of simulation results.

Methods: The mathematical framework includes descriptions of the needle, the resulting potential field, and the active nerve fiber.

Electric fields in tumors exposed to external voltage sources: implication for electric field-mediated drug and gene delivery.

The intratumoral field, which determines the efficiency of electric field-mediated drug and gene delivery, can differ significantly from the applied field. Therefore, we investigated the distribution of the electric field in mouse tumors and tissue phantoms exposed to a large range of electric stimuli, and quantified the resistances of tumor, skin, and electrode-tissue interface. The samples used in the study included 4T1 and B16.

Cardiac microimpedance measurement in two-dimensional models using multisite interstitial stimulation.

We analyzed central interstitial potential differences during multisite stimulation to assess the feasibility of using those recordings to measure cardiac microimpedances in multidimensional preparations. Because interstitial current injected and removed using electrodes with different proximities allows modulation of the portion of current crossing the membrane, we hypothesized that multisite interstitial stimulation would give rise to central interstitial potential differences that depend on intracellular and interstitial microimpedances, allowing measurement of those microimpedances. Simulations of multisite stimulation with fine and wide spacing in two-dimensional models that included dynamic membrane equations for guinea pig ventricular myocytes were performed to generate test data ( partial differentialphio).

The perplexing complexity of cardiac arrhythmias: beyond electrical remodeling.

Cardiac arrhythmias continue to pose a major medical challenge and significant public health burden. Atrial fibrillation, the most prevalent arrhythmia, affects more than two million Americans annually and is associated with a twofold increase in mortality. In addition, more than 250,000 Americans each year suffer ventricular arrhythmias, often resulting in sudden cardiac death.

Cell size and communication: role in structural and electrical development and remodeling of the heart.

With the advent of new information about alterations of cardiac gap junctions in disease conditions associated with arrhythmias, there have been major advances in the genetic and metabolic manipulation of gap junctions. In contrast, in naturally occurring cardiac preparations, little is known about cell-to-cell transmission and the subcellular events of propagation or about structural mechanisms that may affect conduction events at this small size scale. Therefore, the aim of this article is to review results that produce the following unifying picture: changes in cardiac conduction due to remodeling cardiac morphology ultimately are limited to changes in three morphologic parameters: (1) cell geometry (size and shape), (2) gap junctions (distribution and conductivity), and (3) interstitial space (size and distribution).

Electric fields within cells as a function of membrane resistivity--a model study.

Externally applied electric fields play an important role in many therapeutic modalities, but the fields they produce inside cells remain largely unknown. This study makes use of a three-dimensional model to determine the electric field that exists in the intracellular domain of a 10-microm spherical cell exposed to an applied field of 100 V/cm. The transmembrane potential resulting from the applied field was also determined and its change was compared to those of the intracellular field.

Feasibility of cardiac microimpedance measurement using multisite interstitial stimulation.

This study was designed to test the hypothesis that analyses of central interstitial potential differences recorded during multisite stimulation with a set of interstitial electrodes provide sufficient data for accurate measurement of cardiac microimpedances. On theoretical grounds, interstitial current injected and removed using electrodes in close proximity does not cross the membrane, whereas equilibration of intracellular and interstitial potentials occurs distant from electrodes widely separated. Multisite interstitial stimulation should therefore give rise to interstitial potential differences recorded centrally that depend on intracellular and interstitial microimpedances, allowing independent measurement.

Field stimulation of 2-D sheets of excitable tissue.

This paper develops equations for the transmembrane potentials (Vm) that occur in two-dimensional (2-D) sheets of tissue in response to field stimulation from an electrode near but not on the surface of the tissue. Comparison of results with those for one dimension shows that an additional term is present in the 2-D equations that influences the evolution of Vm in the interval between the end of the stimulus and the active propagation that may follow. The results provide an analytical framework for understanding Vm in response to field stimulation in two dimensions, both during the tissue's critical linear phase and thereafter.

Interactions between extracellular stimuli and excitation waves in an atrial reentrant loop.

Unlabelled: Extracellular Stimuli in an Atrial Reentrant Loop.

Introduction: The interactions between extracellular stimuli and excitation waves propagating in a reentrant loop are a complex function of stimulus parameters, structural properties, membrane state, and timing. Here the goal was a comprehensive understanding of the mechanisms and frequencies of the major interactions between the advancing excitation wave and a single extracellular stimulus, separated from issues of anatomic or geometric complexity.

Electrode systems for measuring cardiac impedances using optical transmembrane potential sensors and interstitial electrodes--theoretical design.

The cardiac electrical substrate is a challenge to direct measurement of its properties. Optical technology together with the capability to fabricate small electrodes at close spacings opens new possibilities. Here, those possibilities are explored from a theoretical viewpoint.

Membrane current from transmembrane potentials in complex core-conductor models.

Core-conductor models, used to integrate the behavior of the longitudinal currents with the distributed voltages of electrically active tissue, have evolved for over a century. A critical step in the use of such models is the computation of membrane current from the set of distributed transmembrane potential values that exist at a given moment, where the potentials are obtained either experimentally or computationally. Over time, interest has developed in a number of substantial extensions of the original model to include such features as nonuniform spatial resistances, loop instead of linear structure, and multiple sites of extracellular stimulation.