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PubMed1977

Partial preparative separation and properties of the isoinhibitors of human alpha 1-antitrypsin (alpha 1-protease inhibitor).

Human lapha 1-antitrypsin (alpha 1-protease inhibitor) was chromatographed on a DEAE-cellulose column at pH 6.4. After elution with a linearly increasing concentration of NaCl, five pools (pools I-V) were formed from the eluate, pool I corresponding to the lowest and pool V to the highest concentration of salt. As demonstrated by analytical isoelectric focusing, with increasing concentrations of NaCl the concentration of the cathodal isoinhibitors gradually decreased and the concentration of the anodal ones increased in the pools. Pool I contained only three cathodal and pool V only three anodal isoinhibitors with a limited overlap between the pools. In contrast with the isoinhibitor composition, the sialic acid contents of the pools did not vary with the elution conditions. In line with the chemical evidence, desialylation of the fractions did not affect their electrofocusing positions relative to one another and did not abolish the microheterogeneity of the protein.

Chemical Phenomena↗
PubMed2000

New currents in electrical stimulation of excitable tissues.

Electric fields can stimulate excitable tissue by a number of mechanisms. A uniform long, straight peripheral axon is activated by the gradient of the electric field that is oriented parallel to the fiber axis. Cortical neurons in the brain are excited when the electric field, which is applied along the axon-dendrite axis, reaches a particular threshold value. Cardiac tissue is thought to be depolarized in a uniform electric field by the curved trajectories of its fiber tracts. The bidomain model provides a coherent conceptual framework for analyzing and understanding these apparently disparate phenomena. Concepts such as the activating function and virtual anode and cathode, as well as anode and cathode break and make stimulation, are presented to help explain these excitation events in a unified manner. This modeling approach can also be used to describe the response of excitable tissues to electric fields that arise from charge redistribution (electrical stimulation) and from time-varying magnetic fields (magnetic stimulation) in a self-consistent manner. It has also proved useful to predict the behavior of excitable tissues, to test hypotheses about possible excitation mechanisms, to design novel electrophysiological experiments, and to interpret their findings.

Animals↗
PubMedDate not supplied

High-fidelity electronic display of digital radiographs.

A fully digital radiography system requires high-fidelity electronic display devices that preserve diagnostic quality. Current cathode-ray tube monitors do not meet desired performance criteria for displaying radiographs and have excessive size, weight, and power consumption. Recent developments in flat-panel display technology (in particular active-matrix liquid crystal displays, field-emission displays, and organic light-emitting displays) suggest that high-fidelity, lightweight displays will be available in the near future. Large-size active-matrix liquid crystal display devices have been demonstrated. High brightness can be easily achieved with bright back illumination. Further developments in optical design for monochrome displays should provide high fidelity and improve the angular dependence of the emitted light. Field-emission display devices have attractive emission distribution and potential for low veiling glare. This technology needs to be extended to a large area, and problems with cathode aging and nonuniformity have to be contemplated. Organic light-emitting displays represent a simple and potentially inexpensive display technology with the ability to achieve high image quality. However, extensive research and development is required to achieve large-area manufacturing methods.

Computer Terminals↗
PubMed1981

Quantitative and qualitative comparison of two microfocus-tube imaging systems.

Two microfocus-tube magnification systems were compared: one used an RSI tube (stationary anode, Pierce-gun cathode) and the other used a GE tube (rotating anode, biased cathode). Imaging parameters for body parts of three thicknesses, the hand (low), knee (medium), and hip (high), were considered at a magnification of 2. The focal-spot MTF was measured on and off the central ray of the beam, as well as beam quality and the intensity of scatter in the image plane. Patient exposures were also determined. While both systems gave high-quality images at acceptable exposure levels, the RSI unit was judged superior for body parts up to 15 cm thick. For thicker parts, scatter degraded contrast with the RSI unit, making the GE unit superior.

Humans↗
PubMed2003

Effects of electroporation on optically recorded transmembrane potential responses to high-intensity electrical shocks.

The outcome of defibrillation shocks is determined by the nonlinear transmembrane potential (DeltaVm) response induced by a strong external electrical field in cardiac cells. We investigated the contribution of electroporation to DeltaVm transients during high-intensity shocks using optical mapping. Rectangular and ramp stimuli (10-20 ms) of different polarities and intensities were applied to the rabbit heart epicardium during the plateau phase of the action potential (AP). DeltaVm were optically recorded under a custom 6-mm-diameter electrode using a voltage-sensitive dye. A gradual increase of cathodal and well as anodal stimulus strength was associated with 1) saturation and subsequent reduction of DeltaVm; 2) postshock diastolic resting potential (RP) elevation; and 3) postshock AP amplitude (APA) reduction. Weak stimuli induced a monotonic DeltaVm response and did not affect the RP level. Strong shocks produced a nonmonotonic DeltaVm response and caused RP elevation and a reduction of postshock APA. The maximum positive and maximum negative DeltaVm were recorded at 170 +/- 20 mA/cm2 for cathodal stimuli and at 240 +/- 30 mA/cm2 for anodal stimuli, respectively (means +/- SE, n = 8, P = 0.003). RP elevation reached 10% of APA at a stimulus strength of 320 +/- 40 mA/cm2 for both polarities. Strong ramp stimuli (20 ms, 600 mA/cm2) induced a nonmonotonic DeltaVm response, reaching the same largest positive and negative values as for rectangular shocks. The transition from monotonic to nonmonotonic morphology correlates with RP elevation and APA reduction, which is consistent with cell membrane electroporation. Strong shocks resulted in propidium iodide uptake, suggesting sarcolemma electroporation. In conclusion, electroporation is a likely explanation of the saturation and nonmonotonic nature of cellular responses reported for strong electric stimuli.

Action Potentials↗
PubMed1997

Dose-dependent reduction of cardiac transmembrane potential by high-intensity electrical shocks.

Cardiac tissue dysfunction can result from high-intensity electrical shocks and is manifested as changes in transmembrane potential (Vm). Ten-millisecond shock pulses (SPs) of varying intensity and polarity were applied to frog ventricle in diastole, and Vm was quantified directly under the stimulating electrode by an optical method using voltage-sensitive dye. As SP intensities were increased, the shock-induced action potential (AP) plateau and AP amplitude (APAs) decreased sigmoidally toward 75-85% of the control AP amplitude (APAc) and zero, respectively. APAs was shifted toward lower current densities for anodal compared with cathodal SPs (half-maximal values 185 and 238 mA/cm2, respectively; P = 0.02). Recovery of APAs was marginally significant 1 s after SP delivery (P = 0.063). The peak change in Vm during SP (across all intensity levels) was -200% APAc for anodal and +125% APAc for cathodal pulses. In conclusion, we show that SP reduces APA in a sigmoidal fashion at strengths > 10-20 x diastolic threshold and is more deleterious for anodal polarities.

Action Potentials↗
PubMed2002

Effects of uniform electric fields on intracellular calcium transients in single cardiac cells.

Although intracellular calcium ([Ca(2+)](i)) transients in cardiac cells have been well studied in the uniformly polarized cell membrane, how these transients are modified during field stimulation when the cell membrane is nonuniformly polarized has not been investigated. In this study we characterized the effects of uniform field stimuli on [Ca(2+)](i) transients in isolated guinea pig cardiac cells. Single guinea pig cells were enzymatically isolated, loaded with the [Ca(2+)](i) fluorescent indicator fluo-3, and stimulated along their longitudinal axes with S1 or S1-S2 (S1-S2 = 50 ms) pulses. The fluorescence signals were recorded simultaneously from up to 12 sites along the cell length using a multisite mapping system. S1 pulse, applied during the resting phase of the action potential, induced [Ca(2+)](i) transients that had an earlier onset at the anodal-facing end, suggesting that [Ca(2+)](i) gradients (nabla[Ca(2+)](i)) develop during the rising phase of the [Ca(2+)](i) transients. With the assumption that the peak change in [Ca(2+)](i) is 980 nM, nabla[Ca(2+)](i) was estimated to be approximately 3.4 nM/microm in the anodal half of the cell for a nominal 10 V/cm field and negligible in the cathodal half. The S2 pulse that was applied during the plateau of the action potential also perturbed the [Ca(2+)](i) transients and produced [Ca(2+)](i) gradients directed from the center to either end of the cell. Mean nabla[Ca(2+)](i) in the anodal half of the cell (approximately 4.2 nM/microm) was found to be statistically higher than in the cathodal half (approximately 2.8 nM/microm).

Animals↗
PubMed1980

Effect of anodal blockade of myelinated fibers on vagal C-fiber afferents.

The effects of monopolar cathodal, monopolar anodal, and bipolar anodal polarizing currents on vagal A- and C-fiber activity were studied in anesthetized dogs. Monopolar cathodal polarization consistently produced excitation of spontaneous and evoked A- and C-fibers. Monopolar anodal and bipolar anodal polarizations differentially blocked A-fibers as a function of fiber diameter. The specific purpose of this study was to compare the effects of monopolar anodal and bipolar anodal currents on C-fiber excitability. Small fiber preparations were dissected from the vagal trunk, cut centrally, and placed on recording electrodes. A constant-current stimulus pulse was applied to the nerve at various distances from the blocking electrodes. The stimulus current strength was increased until an isolated C-fiber spike was observed. This value was defined as 100% of threshold. The stimulus current was then reduced to zero, the blocking current was increased slowly to 100 microA, and the procedure repeated. Threshold data obtained in this manner for each set of stimulation electrodes was plotted as a function of distance from the blocking electrode(s) for both modes of anodal blockade. No significant change in C-fiber excitability was observed with bipolar anodal blockade, whereas excitability was significantly (P less than or equal to 0.05) decreased using the monopolar technique. Thus, monopolar anodal block may reduce the possibility of asynchronous C-fiber discharge, which has been associated with a bipolar block of A-fibers.

Afferent Pathways↗
PubMed1981

A combined transcutaneous PO2-PCO2 electrode with electrochemical HCO3- stabilization.

Combined transcutaneous PO2-PCO2 electrodes are described in which the interaction between the two electrodes due to OH- production at the O2 cathode has been eliminated. An anode of either anodized aluminum or platinum has been driven at a current equal to cathode current to force stoichiometric consumption of OH- at its rate of production. The AgCl reference electrode operates at zero current. O2 sensitivity was not significantly altered by electrolyte pH variation from 6.7 to 9.0 with variations by PCO2. These electrodes have been found stable both with and without spacers, and with electrolytes dissolved in 50-100% ethylene glycol. In 22 anesthetized patients, with electrode temperature of 43 degrees C (s refers to skin surface, a to arterial blood); PsO2 = 0.52PaO2 + 15 (range 54-300) (r = 0.66; Sy . x = 29.6; n = 46); and PsCO2 = 1.39PaCO2 + 2.1 (range 24-98) (r = 0.99; Sy . x = 2.28; n = 48).

Bicarbonates↗
PubMed1993

Generation and transit pathway of H+ is critical for inhibition of palmar sweating by iontophoresis in water.

Passing galvanic current across the skin (known as "tap water iontophoresis" or TWI) inhibits sweating; however, its mechanism of action is unclear. Using improved methods, we confirmed that anodal current has more of an inhibitory effect than cathodal current, water is superior to saline, and the inhibitory effect is a function of the amperage used. To address the importance of current flowing through the pores, a layer of silicone grease was placed on the skin to reduce the shunt pathway across the epidermis. With silicone, total skin conductance decreased 60% without the sweat pores being occluded, swelling of the stratum corneum and collapse of the poral lumen was prevented, and current-induced inhibition of sweating was enhanced, most likely because of an increase in current density in the pores. The pH of anodal water, but not of saline, dropped to 3, whereas that of cathodal water increased to 10 during passage of current through the skin. Acidified anodal water was superior to alkaline water. Sweat glands isolated from TWI-induced anhidrotic palmar skin responded to methacholine in vitro, but the sweat rate and pharmacological sensitivity were slightly lowered. Thus the strong acidity generated by hydrolysis of water in the anodal bath and the further accumulation of H+ in the sweat duct by anodal current may be responsible for TWI-induced inhibition of sweating due to an unknown lesion(s) in the duct or sweat pore. The secretory coil function may also be altered because of exposure to intense acidity during TWI. The importance of H+ movement into the sweat pore for inhibition of sweating could be further exploited to develop new strategies for the control of sweating.

Adolescent↗
PubMed1975

An electrically mediated inhibition in goldfish medulla.

1. Passive hyperpolarizing potentials (PHPs) have been recorded intracellularly from goldfish medullary neurons in the vicinity of the Mauthner cell (M-cell). They are evoked when this cell is activated antidromically by stimulation of the spinal cord, and orthodromically via the ipsilateral eighth nerve; when appropriately timed they block or delay spikes induced both directly and transsynaptically. 2. Since the PHPs and the M-cell spike have the same latency, time course, and all-or-none character, they cannot be generated by chemically mediated synaptic transmission. This conclusion is further supported by the evidence that PHP amplitude and time course are independent of membrane potential. 3. The analysis of the mechanism underlying PHP generation has been based on the hypothesis that they are brought about by the extracellular currents flowing to the axon cap during an M-cell action potential. Specifically, it was postulated that some of this current is channeled back to the axon cap region intracellularly through processes of PHP-exhibiting neurons, and that these cells are passively hyperpolarized by the associated inward transmembrane current flow. This model would require that PHP-exhibiting neurons send processes into the axon cap. This hypothesis is confirmed by the following: a) When the PHP is timed to occur during the conductance increase associated with a spike after hyperpolarization, it is reduced, as would be expected for a passive current flow across a membrane resistance. b) PHPs are not found in all medullary neurons in the vicinity of the M-cell, but rather in a specific neuronal population. c) PHP-exhibiting neurons have been identified following Procion yellow injections; as predicted, they issue one process, presumably the axon, which projects toward the M-cell axon cap area. d) The PHP can be stimulated by passing a cathodal current from a microelectrode located in the axon cap; it is not mimicked when the cathodal electrode is moved outside this region. The currents necessary to mimic a PHP are comparable to the estimated current flowing back to the axon cap during an M-cell action potential. 4. The input resistance of PHP-exhibiting neurons is in the range of 4 M alpha, and their estimated specific membrane resistance is in the range of 900-2,000 alpha-cm-2, which is not an unusually low value for neuronal membranes. By contrast, the intracellular channeling of current during a PHP can rather be attributed to a high extracellular tissue resistance within the axon cap, which was found to be at least 2.5 times that of the surrounding medullary tissue..

Action Potentials↗
PubMed2000

Primate translational vestibuloocular reflexes. III. Effects of bilateral labyrinthine electrical stimulation.

The effects of functional, reversible ablation and potential recruitment of the most irregular otolith afferents on the dynamics and sensitivity of the translational vestibuloocular reflexes (trVORs) were investigated in rhesus monkeys trained to fixate near and far targets. Translational motion stimuli consisted of either steady-state lateral and fore-aft sinusoidal oscillations or short-lasting transient lateral head displacements. Short-duration (usually <2 s) anodal (inhibitory) and cathodal (excitatory) currents (50-100 microA) were delivered bilaterally during motion. In the presence of anodal labyrinthine stimulation, trVOR sensitivity and its dependence on viewing distance were significantly decreased. In addition, anodal currents significantly increased phase lags. During transient motion, anodal stimulation resulted in significantly lower initial eye acceleration and more sluggish responses. Cathodal currents tended to have opposite effects. The main characteristics of these results were simulated by a simple model where both regularly and irregularly discharging afferents contribute to the trVORs. Anodal labyrinthine currents also were found to decrease eye velocity during long-duration, constant velocity rotations, although results were generally more variable compared with those during translational motion.

Algorithms↗
PubMed2002

Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output.

The objective of this project was to examine the influence of stimulus waveform and frequency on extracellular stimulation of neurons with their cell bodies near the electrode (local cells) and fibers of passage in the CNS. Detailed computer-based models of CNS cells and axons were developed that accurately reproduced the dynamic firing properties of mammalian motoneurons including afterpotential shape, spike-frequency adaptation, and firing frequency as a function of stimulus amplitude. The neuron models were coupled to a three-dimensional finite element model of the spinal cord that solved for the potentials generated in the tissue medium by an extracellular electrode. Extracellular stimulation of the CNS with symmetrical charge balanced biphasic stimuli resulted in activation of fibers of passage, axon terminals, and local cells around the electrode at similar thresholds. While high stimulus frequencies enhanced activation of fibers of passage, a much more robust technique to achieve selective activation of targeted neuronal populations was via alterations in the stimulus waveform. Asymmetrical charge-balanced biphasic stimuli, consisting of a long-duration low-amplitude cathodic prepulse phase followed by a short-duration high-amplitude anodic stimulus phase, enabled selective activation of local cells. Conversely, an anodic prepulse phase followed by a cathodic stimulus phase enabled selective activation of fibers of passage. The threshold for activation of axon terminals in the vicinity of the electrode was lower than the threshold for direct activation of local cells, independent of the stimulus waveform. As a result, stimulation induced trans-synaptic influences (indirect depolarization/hyperpolarization) on local cells altered their neural output, and this indirect effect was dependent on stimulus frequency. If the indirect activation of local cells was inhibitory, there was little effect on the stimulation induced neural output of the local cells. However, if the indirect activation of the local cells was excitatory, attempts to activate selectively fibers of passage over local cells was limited. These outcomes provide a biophysical basis for understanding frequency-dependent outputs during CNS stimulation and provide useful tools for selective stimulation of the CNS.

Animals↗
PubMed1989

Cell surface changes during electromagnetic field exposure.

Fibroblasts from 5 1/2-day-old chick embryos go through a sequential series of changes when exposed to a constant electromagnetic field (EMF) of 10 V/cm. These changes include rounding up, becoming bipolar in shape, assuming a cylindrical profile, elongating perpendicular to the EMF, and migrating to the cathode. These morphological changes are associated with changes of the cell surface, which include the formation of filopodia and extensive sheet-like contacts on the cathodic cell surface, the retraction of processes and the formation of focal contacts on the anodic cell surface.

Animals↗
PubMed1977

Evidence of agar gel electrophoresis changes of lipoprotein-X after phospholipase A and deoxycholic acid.

The effect of phospholipase A from snake venom and deoxycholic acid on lipoprotein-X (LP-X) recovered from the cathode side of a previous agar gel electrophoresis is described. Adding phospholipase A and deoxycholic acid to the removed cathodal fraction is followed by a marked migration to the anode side on a second electrophoresis procedure. This seems to confirm that phospholipase A and bile salts on LP-X particles modifying their agar gel electrophoretic migration characteristics.

Cholestasis↗
PubMed1996

Calf lens alpha-crystallin, a molecular chaperone, builds stable complexes with beta s- and gamma-crystallins.

Calf water-soluble (WS) crystallins consist of high-molecular weight (HM), alpha-, beta H-, beta L-, beta s- and gamma-crystallins. alpha-Crystallin as a molecular chaperone forms a structure with a central hole, known as Carver's model. The only crystallins fitting into this central cavity are beta s- and gamma-crystallins, with native molecular weights of 28 and 18.5-21 kD, respectively. The beta s-crystallin is loosely bound to this structure, whereas with the application of 7M urea in the sample, beta s-, may be some beta L-components and all gamma-crystallins emerge from the central hole. Although WS and water-insoluble (WI) crystallins display the same immunologic determinants, there is an appreciable difference in electrophoretic mobility already in the young calf lens. alpha-Crystallins from the WI part demonstrate a clear cathodic shift. WI beta- and gamma-crystallins show smaller but well perceptible cathodic shifts. The chaperone function of alpha-crystallin preserves the original structures of beta s- and gamma-crystallins for aggregation and other influences.

Animals↗
PubMed2004

Intramural virtual electrodes in ventricular wall: effects on epicardial polarizations.

BACKGROUND: Intramural virtual electrodes (IVEs) are believed to play an important role in defibrillation, but their existence in intact myocardium remains unproven. Here, IVEs were detected by use of optical recordings of shock-induced transmembrane potential (V(m)) changes (DeltaV(m)) measured from the intact epicardial heart surface. METHODS AND RESULTS: To detect IVEs, isolated porcine left ventricles were sequentially stained with a V(m)-sensitive dye by 2 methods: (1) surface staining (SS) and (2) global staining (GS) via coronary perfusion. Shocks (2 to 50 V/cm) were applied across the ventricular wall in an epicardial-to-endocardial direction during the action potential plateau via transparent mesh electrodes, and shock-induced DeltaV(m) were measured optically from the same epicardial locations after SS and GS. Optical recordings revealed significant differences between DeltaV(m) of 2 types that became more prominent with increasing shock strength: (1) for weak shocks, SS-DeltaV(m) were larger and faster than GS-DeltaV(m); (2) for intermediate shocks, cathodal GS-DeltaV(m) became multiphasic, whereas SS-DeltaV(m) remained monophasic; and (3) for strong shocks, cathodal GS-DeltaV(m) became uniformly negative, whereas SS-DeltaV(m) typically remained positive. The radical differences in the shape and polarity of SS and GS polarizations can be explained by the contribution of subepicardial IVEs to optical signals. Histological examination revealed a dense network of collagen septa in the subepicardium, which could form the IVE substrate. CONCLUSIONS: Intramural virtual electrodes are reflected in optical measurements of shock-induced DeltaV(m) on the intact epicardial surface. These IVEs could be a result of microscopic resistive discontinuities formed by collagen septa.

Action Potentials↗
PubMed1986

Internal cardiac defibrillation in man: pronounced improvement with sequential pulse delivery to two different lead orientations.

Wider applicability of an implantable automatic defibrillator depends on achieving internal cardiac defibrillation consistently with the lowest possible energy. In animal studies, we have found that the cardiac defibrillation threshold could be reduced when sequential shocks separated in time and spacially arranged were delivered to the heart. We compared internal cardiac defibrillation using a single pulse shock delivered through an intravascular catheter with this new method for internal cardiac defibrillation in patients undergoing cardiac surgery for the correction of arrhythmias. For the single pulse shock and the first pulse of the sequential pulse shock, current was passed through an intravascular catheter with the catheter cathode at the apex of the right ventricle and the anode at the superior vena cava-atrial junction region. The second pulse of the sequential pulse countershock was delivered between the catheter cathode in the right ventricular apex and an oval plaque electrode secured on the laterobasal left ventricular epicardium as anode. With the single pulse alone for shock delivery, 12 patients could be defibrillated with an average of 20.1 +/- 16.8 J, with a corresponding leading-edge peak voltage and current of 836 +/- 319 V and 9.4 +/- 4.5 A, respectively. However, two of the patients could not be defibrillated with energies below 50 J. With the sequential pulse shock delivery, a significant reduction in all values were recorded. Mean total energy for defibrillation averaged 7.7 +/- 6.0 J. Leading-edge peak voltage and current from the catheter averaged 430 +/- 148 V and 5.0 +/- 2.8 A, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗