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Biomedical subjects

Bradley J Roth

Publications and source records attributed to Bradley J Roth.

At least 19 recordsLinked to original sources
PubMed2006

Quatrefoil reentry caused by burst pacing.

BACKGROUND: Experiments and clinical studies have shown that high-frequency (burst) pacing can induce reentry and fibrillation without a strong shock. We hypothesize that a train of weak stimuli induces quatrefoil reentry, and investigate the mechanism and threshold for this mode of reentry induction. METHODS: We apply a train of weak stimuli at different pacing rates to determine the threshold necessary to induce quatrefoil reentry. Numerical calculations are used to simulate cardiac tissue, based on the bidomain model with unequal anisotropy ratios. We consider both anodal and cathodal stimuli. RESULTS: Quatrefoil reentry is initiated using much smaller currents during burst pacing (0.9 mA) compared to a single premature pulse (8.6 mA). As we varied the pacing rate, we observed reentry at the border between different modes of phase locking, such as between 1:1 and 2:1 responses. CONCLUSION: Burst pacing can significantly reduce the threshold for reentry. However, the extreme sensitivity of reentry induction to the exact number of stimuli in the pulse train makes the method difficult to use as a consistent, reproducible way to induce reentry.

Action Potentials↗
PubMed2006

The effect of the cut surface during electrical stimulation of a cardiac wedge preparation.

Optical mapping from the cut surface of a "wedge preparation" allows observation inside the heart wall, below the epicardium or endocardium. We use numerical simulations based on the bidomain model to illustrate how the transmembrane potential is influenced by the cut surface. The distribution of transmembrane potential around a unipolar cathode depends on the fiber angle. For intermediate angles, hyperpolarization appears on only one side of the electrode, and is large and widespread.

Action Potentials↗
PubMed2006

The effect of the fiber curvature gradient on break excitation in cardiac tissue.

BACKGROUND: Break excitation has been hypothesized as a mechanism for the initiation of reentry in cardiac tissue. One way break excitation can occur is by virtual electrodes formed due to a curving fiber geometry. In this article, we are concerned with the relationship between the peak gradient of fiber curvature and the threshold for break stimulation and the initiation of reentry. METHODS: We calculate the maximum gradient of fiber curvature for different scales of fiber geometry in a constant tissue size (20x20 mm), and also examine the mechanisms by which reentry initiation fails. RESULTS: For small peak gradients, reentry fails because break excitation does not occur. For larger peak gradients, reentry fails because break excitation fails to develop into full-scale reentry. For strong stimuli above the upper limit of vulnerability, reentry fails because the break excitation propagates through the hyperpolarized region and then encounters refractory tissue, causing the wave front to die.

Action Potentials↗
PubMed2005

Approximate solution to the bidomain equations for electrocardiogram problems.

Simulating the electrocardiogram requires specifying the transmembrane potential distribution within the heart and calculating the potential on the surface of the body. Often, such calculations are based on the bidomain model of cardiac tissue. A subtle but fundamental problem arises when considering the boundary between the cardiac tissue and the surrounding volume conductor. In general, one finds that two potentials--the extracellular potential in the tissue and the potential in the surrounding bath--obey three boundary conditions, implying that the potentials are overdetermined. In this paper, we derive a general method for handling bidomain boundary conditions that eliminates this problem. The gist of the method is that we add an additional term to the transmembrane potential that falls exponentially with depth into the tissue. The purpose of this term is to satisfy the third boundary condition. Then, we take the limit as the length constant associated with this extra term goes to zero. Our result is two boundary conditions that approximately account for the full set of three boundary conditions at the tissue surface.

Action Potentials↗
PubMed2005

Optical measurements reveal nature of intercellular coupling across ventricular wall.

Previously, we showed that intercellular uncoupling through gap junctions is an important mechanism for maintaining transmural heterogeneities of repolarization that are responsible for ventricular arrhythmias in disease states such as heart failure. However, rotational anisotropy between transmural muscle layers also may influence coupling. To determine the effect of rotational anisotropy on transmural coupling, we developed a numerical three-dimensional model of passive cardiac tissue in which rotational anisotropy was varied in a controlled fashion. Simulations of optical mapping demonstrated that spatial averaging produced a voltage decay in space best fit by a single decaying exponential compared with the theoretically predicted decay. As fiber orientation varied by 90 degrees with respect to the transmural surface, the effective transmural space constant (lambda(TM)) changed by only 0.31% in simulations. In contrast, reducing intercellular conductivity by 24% decreased lambda(TM) by 7.7%. In the canine wedge preparation (n = 5), lambda measured by optical mapping of the epicardial and subepicardial surface was similar transverse (lambda(TV) = 0.73 +/- 0.10 mm) and transmural (lambda(TM) = 0.70 +/- 0.08 mm) to subepicardial fibers. We confirmed previous findings that lambda(TM) in subepicardial layers was significantly reduced by 14 +/- 2% compared with deeper layers of myocardium, providing evidence for transmural uncoupling in the epicardial-midmyocardial interface. These data establish the theoretical and experimental basis for measuring intercellular coupling between muscle layers spanning the ventricular wall with optical mapping techniques. Furthermore, this study demonstrates that transmural uncoupling at the epicardial-midmyocardial interface may be attributable to heterogeneous expression of cardiac gap junctions and not rotational anisotropy.

Action Potentials↗
PubMed2005

Approximate solution to the bidomain equations for defibrillation problems.

The bidomain model can be used for calculating the electrical potential in the heart during defibrillation. However, this model consists of a coupled system of two partial differential equations that are, in general, difficult and time consuming to solve. In this paper, we present an approximate, iterative method of solving the bidomain equations. After working out the general method, we apply it to four problems: (i) a cylindrical strand in a uniform electric field, (ii) a nonuniform electric field applied to tissue with straight fibers, (iii) a spherical heart in a uniform electric field, and (iv) a two-dimensional sheet of cardiac tissue with curving fibers. Finally, we analyze the general case of three dimensions.

Action Potentials↗
PubMed2005

Automating phase singularity localization in mathematical models of cardiac tissue dynamics.

Electrical wave-fronts are responsible for contraction in heart tissue. Rotary wave-fronts break up into daughter waves and it is this break up that is believed to underlie ventricular fibrillation. Mathematical methods abound for simulation of fibrillation, and localizing the core of rotary wave-fronts (the phase singularities) is key to characterizing the state of fibrillation and effectiveness of defibrillation in these models. We present a formal method for automating this process in these various models. Automation will allow for side-by-side comparisons of suggested mechanisms of fibrillation, comparison of various models of these mechanisms and faster evaluation of defibrillation strategies making use of these models.

Action Potentials↗
PubMed2005

How the spatial frequency of polarization influences the induction of reentry in cardiac tissue.

UNLABELLED: Influences of spatial frequency of polarization. INTRODUCTION: The mechanism by which an electric field induces a rotor during cross-field stimulation of cardiac tissue is not entirely known. Different heterogeneous aspects of cardiac tissue have been offered as possible theories, a prominent one being fiber curvature. The polarization produced when an electric field is applied to a sheet of tissue is varied over many spatial frequencies, depending upon the fiber angle. This article compares the effect of high and low spatial frequencies of polarization on reentry induction. METHODS AND RESULTS: We incorporate a randomized fiber angle geometry into a two-dimensional active cardiac tissue model with unequal anisotropy ratios already exhibiting smooth, curving fibers. We simulate cross-field stimulation to initiate reentry in the tissue model, and compare the electric field thresholds at different S1-S2 intervals for tissue with randomized fiber angles, tissue with a smooth fiber geometry, and tissue with randomized fiber angles plus smooth, curving fibers. The tissue with both small, random fiber angles and curving fibers has a significantly lower threshold for reentry at certain intervals on the strength-interval curve than for the two cases individually. CONCLUSION: Cardiac tissue exhibiting a random fiber geometry in conjunction with a smooth fiber geometry includes high and low spatial frequencies of polarization that may have an effect on the mechanism for reentry at certain S1-S2 intervals. Low spatial frequency regions of hyperpolarization carve out excitable pathways, and high spatial frequency regions provide the large gradient of transmembrane potential required to initiate break excitation.

Anisotropy↗
PubMed2004

Art Winfree and the bidomain model of cardiac tissue.

This paper reviews Art Winfree's contributions to the bidomain model of cardiac tissue. Specifically, he first predicted quatrefoil reentry, he showed that an S1 refractory gradient is not required for an S2 stimulus to induce reentry, and his work on spiral wave meandering led to studies on how the path of the tip of a spiral wave is influenced by tissue anisotropy.

Cardiology↗
PubMed2004

A mathematical model for electrical stimulation of a monolayer of cardiac cells.

BACKGROUND: The goal of our study is to examine the effect of stimulating a two-dimensional sheet of myocardial cells. We assume that the stimulating electrode is located in a bath perfusing the tissue. METHODS: An equation governing the transmembrane potential, based on the continuity equation and Ohm's law, is solved numerically using a finite difference technique. RESULTS: The sheet is depolarized under the stimulating electrode and is hyperpolarized on each side of the electrode along the fiber axis. CONCLUSIONS: The results are similar to those obtained previously by Sepulveda et al. (Biophys J, 55: 987-999, 1989) for stimulation of a two-dimensional sheet of tissue with no perfusing bath present.

Algorithms↗
PubMed2004

Effect of plunge electrodes in active cardiac tissue with curving fibers.

OBJECTIVES: Our goal is to determine if plunge electrodes change how the heart responds to electrical stimulation. BACKGROUND: Several experiments designed to study the induction of a rotor in cardiac tissue have used plunge electrodes to measure the transmural potential. It is our hypothesis that these electrodes may have affected the electrical response of the tissue to a shock. METHODS: We previously have shown that a single plunge electrode in two-dimensional, passive cardiac tissue induces a significant transmembrane potential when stimulated by a large shock. In this study, we expand our simulation to include an array of nine electrodes in active tissue with curving fibers. We compare the thresholds for rotor induction in tissue with and without electrodes by initiating a planar S1 wavefront and then stimulating the tissue at different intervals with a uniform S2 electric field perpendicular to S1. In tissue without plunge electrodes, virtual electrode polarization due to the curving fibers is generally widespread over the entire tissue, whereas polarization tends to be localized around the electrodes in tissue including them. RESULTS: Our results show that at some S1-S2 intervals, the presence of plunge electrodes can result in reentry when it otherwise would not be possible. For other S1-S2 intervals, such as during the vulnerable period when the reentry threshold is at a minimum, the induction of reentry is unaffected by the presence of plunge electrodes. CONCLUSIONS: Plunge electrodes can play an important role during the stimulation of cardiac tissue, but this is highly dependent on the chosen S1-S2 interval.

Artifacts↗
PubMed2004

Cardiac optical mapping under a translucent stimulation electrode.

Major effects of stimulation on cardiac transmembrane potentials (Vm) are thought to occur under the electrode, however these have not been optically mapped due to blockage of light by electrodes. Here we optically mapped under translucent indium tin oxide (ITO) electrodes in hearts stained with transmembrane voltage sensitive fluorescent dye, di-4-ANEPPS excited at 488 nm. Emissions in wavelength bands 510-570 nm and >590 nm were similarly affected by changes in ITO transmittance due to electrochemical effects of current at the electrode interface. Dual-wavelength ratiometric mapping with the two emission bands revealed Vm under the electrode during plateau-phase stimulation (220 mA). Changes in Vm were heterogeneous under the electrode, and were anisotropic with larger values along the fiber axis. These results explain early excitation sites for sufficiently strong diastolic stimulation, and agree with theoretical predictions based on summation of anisotropic effects of point stimulation and a linear 3-d cardiac bidomain computer model. The bidomain model and experiments disagree under the edge of the electrode, where modeled Vm is much larger. Thus, changes in Vm under an electrode are anisotropic with greater Vm in the direction parallel to fibers. Nonlinear effects of stimulation in hearts may limit changes in Vm under the electrode edge.

Animals↗
PubMed2003

Approximate analytical solutions of the Bidomain equations for electrical stimulation of cardiac tissue with curving fibers.

The mechanism by which an applied electric field stimulates cardiac tissue far from the stimulating electrodes is not wholly understood. One possible mechanism relates the curving cardiac fibers to the induced membrane currents and transmembrane potentials. However, we lack a qualitative understanding of where these areas of polarization will occur when an electric field is applied to a sheet of cardiac tissue with curving fibers. In our study, we derive an analytical model for the transmembrane potential, dependent on the gradient of the fiber angle theta, for a two-dimensional passive sheet of cardiac tissue exhibiting various fiber geometries. Unequal anisotropy ratios are crucial for our results. We compare the results from our analytical solution to a numerical calculation using the full bidomain model. The results of our comparison are qualitatively consistent, albeit numerically different. We believe that our analytical approximation provides a reliable prediction of the polarization associated with an electric field applied to cardiac tissue with any fiber geometry and a qualitative understanding of the mechanisms behind the virtual electrode polarization.

Animals↗
PubMed2003

Cadaveric organ donor recruitment at Los Angeles County Hospital: improvement after formation of a structured clinical, educational and administrative service.

BACKGROUND/AIMS: There remains a critical shortage of cadaveric organs. At a large inner city level one trauma centre, several strategies were devised and combined to (a). optimize the physiologic status of potential donors, (b). promote awareness of the donation process among health care professionals and (c). perform quality control on the organ donation system - all in an effort to improve organ donation rates. Resuscitative and maintenance protocols were devised and implemented through a multidisciplinary team approach for patients diagnosed with brain death. We report the effect this approach has had on organ donation in a single centre. METHOD: A death record review (DRR) by the local organ procurement agency (OPO) was used to identify the number of patients diagnosed with brain death at Los Angeles County Hospital each year from 1995 through 2001. Data were collected to determine the number of these potential donors that eventually underwent organ donation. Data were collected for two time intervals: Phase I (1995-98) and Phase II (1999-2001). During Phase I, there was no focused institutional programme for the approach to potential donors. During Phase II, an institutional programme including the following characteristics was implemented: 1). donor resuscitation protocol, 2). assignment of a dedicated OPO coordinator liaison to interact with families, hospital personnel and the coroner's office, 3). assignment of the primary role of stabilization and care of potential donors and the integration of all medical services to the trauma service, and 4). biweekly conferences to review policies, protocols, and outcomes of donor management strategies. RESULTS: From 1995 to 2001 there was a large increase in patient referrals for donor evaluation from 86 (Phase I) to 124 (Phase II). There was a smaller increase in the number of suitable donors: Phase I (mean: 51/year) and Phase II (mean: 63/year). There was, however, an increase in the mean number of actual organ donors from 14.2/year to 25.7/year from Phase I to Phase II and an increase in organs donated from 29 to 49. Organ donor declines decreased from 53% (Phase I) to 39% (Phase II). CONCLUSIONS: Strategies to increase the number of cadaveric organs available for organ transplantation are crucial. A strategy combining prompt identification of potential organ donors, institution of resuscitative protocols, a multidisciplinary team approach, educational activities and utilization of personnel expert in organ procurement led to a marked increase in the number of organ donors and the number of organs donated at a single institution. Wider application of this approach should prove successful in increasing organ donation in a similar fashion in other institutions.

Cadaver↗
PubMed2003

Effects of elevated extracellular potassium ion concentration on anodal excitation of cardiac tissue.

INTRODUCTION: Anodal excitation of cardiac tissue occurs by two mechanisms: "make" and "break." Anodal strength-interval curves are divided into two sections, with break excitation occurring at short intervals and make at long intervals. Our goal is to determine how an elevated extracellular potassium ion concentration, [K]o, affects the mechanism of anodal excitation and influences the anodal strength-interval curve. METHODS AND RESULTS: Computer simulations of unipolar stimulation were performed using the bidomain model, with membrane kinetics governed by the Luo-Rudy model. The diastolic threshold for anodal stimulation first decreased and then increased with increasing [K]o, reaching a minimum value at [K]o = 12 mM. The mechanism for diastolic anodal excitation was make for all [K]o values except 13.3 mM, in which case it was break. For low [K]o (4 and 8 mM) the break section of the anodal strength-interval contained a "dip," but for high [K]o (12 and 13 mM), the dip disappeared. CONCLUSION: High [K]o predisposes cardiac tissue to break excitation, which is thought to play an important role in reentry induction and defibrillation. Because fibrillation raises extracellular [K]o levels, break excitation may play a more important role in defibrillation than is suggested by simulations and experiments using normal [K]o values.

Computer Simulation↗