Conduction block in Purkinje fibers by homogeneous versus localized decrease of the gap junction conductance

Gap junction channels provide the pathway for the cell-to-cell propagation of cardiac action potential. Impairment of junctional conductance decreases conduction velocity and can cause block, two conditions that favor ventricular arrhythmias and fibrillation by re-entrant excitation. These experiments were designed to examine the effects of homogeneous versus localized decrease of the gap junction conductance on propagation of action potential in Purkinje fibers from sheep hearts. The fibers were mounted in a three-compartment chamber, and cell-to-cell conductance was progressively reduced by applying heptanol either over a central 2-mm segment or over the whole fiber length. The internal resistivities (Ri) at which conduction of the action potential became blocked were determined in both cases. With 3.5 mM heptanol in the central compartment, conduction failed when Ri was increased by only 3-4.6 times the control values. In contrast, when the same concentration of heptanol was added simultaneously to all three compartments, Ri had to rise by a factor of 7.5-9.4 before conduction became decremental and was blocked. In both situations, dV/dt(max) at the time of conduction block was similarly decreased to about 50% of the control values. Other parameters being equal, a moderate decrease of the gap junction conductance and of the fast sodium current, insufficient to block propagation of the action potential when they are homogeneously distributed, become sufficient to interrupt conduction if the action potential merges abruptly into a portion of fiber with normal internal conductivity at the outlet of the area of increased resistance. This greater sensitivity to block is accounted for by the increase in electrical load at the discontinuity in the core conductor between the region of increased internal resistance and the normal part of fiber that follows. Areas of steep transition from high to low input resistances of the core conductor, such as may develop in localized ischemia, therefore appear particularly susceptible to conduction failure.     

Theoretical evaluation of peripheral nerve stimulation during MRI with an implanted spinal fusion stimulator

This study examines the requirements for nerve excitation near a spinal fusion implant during magnetic resonance imaging. The implant is the Spinal Fusion SpF device manufactured by Electro Biology Inc. The electric field induced within the biological medium was calculated using a three-dimensional finite difference model (described in a separate paper by Beuchler et al. from the University of Utah). Magnetic thresholds were obtained for excitation of myelinated nerve fibers that are near the implant. Minimum (rheobase) thresholds were determined for long duration dB/dt pulses, as well as strength-duration time constants (from which thresholds at other durations could be determined) for various geometries between the implant and a myelinated nerve fiber. The lowest thresholds occur when a large (20-microm diameter) fiber is situated near the bare tip of a wire from the implant, and a long duration (2 ms) stimulus is provided for which dB/dt is constant and monophasic. Magnetic thresholds for shorter durations of dB/dt are higher in accordance with a strength-duration law. In a magnetic field having a time derivative of 10 T/s that is uniform over the torso, nerve excitation is possible under worst-case conditions only for nerve fibers that are within 0.14 mm of the bare wire tip of the implant. With 20 T/s, excitation is possible only within 1 mm of the wire tip.     

Picture naming: An investigation of the nature of categorical priming.

Although there are numerous theories of the structure of semantic memory, a notion central of many of these theories is that of semantic category membership. The present studies represent an investigation of the effects of a semantic category relation between prime and target in a picture-naming task. Because picture naming is presumed to require access to semantic memory, category priming effects were anticipated even when associative and phonetic effects were eliminated. This expectation was verified in Experiment 1. Experiments 2 and 3 were attempts to specify the nature and locus of this categorical priming effect. In particular, it was suggested that one locus would be an entry-level memory system for pictures. Results suggest that this system plays little role in categorical priming of picture naming. Rather, a better explanation would be one based on processing within semantic memory. The possibility of lexical memory acting as an additional locus is also considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synchronization of golgi and granule cell firing in a detailed network model of the cerebellar granule cell layer

The granular layer of the cerebellum has a disproportionately large number of excitatory (granule cells) versus inhibitory neurons (Golgi cells). Its synaptic organization is also unique with a dense reciprocal innervation between granule and Golgi cells but without synaptic contacts among the neurons of either population. Physiological recordings of granule or Golgi cell activity are scarce, and our current thinking about the way the granular layer functions is based almost exclusively on theoretical considerations. We computed the steady-state activity of a large-scale model of the granular layer of the rat cerebellum. Within a few tens of milliseconds after the start of random mossy fiber input, the populations of Golgi and granule cells became entrained in a single synchronous oscillation, the basic frequency of which ranged from 10 to 40 Hz depending on the average rate of firing in the mossy fiber population. The long parallel fibers ensured, through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-mediated synapses, a coherent excitation of Golgi cells, while the regular firing of each Golgi cell synchronized all granule cells within its axonal radius through transient activation of their gamma-aminobutyric acid-A (GABAA) receptor synapses. Individual granule cells often remained silent during a few successive oscillation cycles so that their average firing rates, which could be quite variable, reflected the average activities of their mossy fiber afferents. The synchronous, rhythmic firing pattern was robust over a broad range of biologically realistic parameter values and to parameter randomization. Three conditions, however, made the oscillations more transient and could desynchronize the entire network in the end: a very low mossy fiber activity, a very dominant excitation of Golgi cells through mossy fiber synapses (rather than through parallel fiber synapses), and a tonic activation of granule cell GABAA receptors (with an almost complete absence of synaptically induced inhibitory postsynaptic currents). These three conditions were associated with a reduction in the parallel fiber activity, and synchrony could be restored by increasing the mossy fiber firing rate. The model predicts that, under conditions of strong mossy fiber input to the cerebellum, Golgi cells do not only control the strength of parallel fiber activity but also the timing of the individual spikes. Provided that their parallel fiber synapses constitute an important source of excitation, Golgi cells fire rhythmically and synchronized with granule cells over large distances along the parallel fiber axis. According to the model, the granular layer of the cerebellum is desynchronized when the mossy fiber firing rate is low.     

Effect of immobilization on skeletal muscle nicotinic cholinergic receptors in the rat

The effect of 4 weeks of hind limb immobilization on nicotinic acetylcholinergic receptors (nAChRs) in the neuromuscular junction of the soleus (SOL) and tibialis anterior (TIB) muscles was studied in rats. Quantitative measurements of the receptors was performed using [3H]alpha-bungarotoxin ([3H]alpha-BTx) receptor autoradiography. Junctional and extrajunctional nAChRs were significantly increased in the SOL and TIB after 4 weeks immobilization. However, a significant decrease in fiber cross-sectional area was observed only in the SOL muscle. Remobilization for 4 weeks reversed the changes in cholinergic receptors and muscle fibers but not in bone. Our findings suggested that lack of nerve impulses are of importance for the events that take place after immobilization leading to muscle atrophy and osteoporosis.     

Freezing and storage of breast cancer tissue for estrogen receptor protein assay: a convenient method

The parameters of the Field, Noyes and K?r?s model for the Belousov-Zhabotinskii reaction were chosen in such a way that the given system is excitable. It is shown by simulation that several pulses on the ring fiber, contrary to experience with known excitable media, may arrange themselves in a non-symmetrical manner while the equilibrium distances are stable. The condition for such behavior is the non-monotonic dependence of the propagation velocity, v, on the time, T, elpased since the previous excitation at that point.     

Isotropic fiber coarsening in unidirectionally solidified eutectic alloys

A theory of coarsening has been developed for the case of fibers of circular cross section in unidirectionally solidified eutectic alloys. The fibers are assumed to be randomly distributed throughout the unoccupied space in the matrix (uniformly distributed), and diffusion of solute is assumed to occur under steady-state conditions with cylindrical symmetry. The theory predicts that the cube of the average fiber radius increases linearly with time for all fiber volume fractions. As the volume fraction increases, the coarsening rate increases and the theoretical distribution of fiber radii becomes broader. It is shown that isotropic fiber coarsening occurs at approximately half the rate at which the same phase would coarsen if it were in the form of spherical precipitates for volume fractions up to 0.6. It is also demonstrated that the fibers will coarsen at a faster rate when they are uniformly distributed than when they are arranged on an hexagonal lattice.     

Role of the net architecture in piriform cortex activity: analysis by a mathematical model

We present a mathematical analysis of the piriform cortex activity in rats. Experimental data were obtained by means of optical recording of fluorescent signals driven by neuronal activity. From these data, we determined the numerical value of the relaxation time for the pyramidal cell activity in layers II and III and the time latency map for bulb activation. Our model for the piriform cortex is based on pairs of excitatory and inhibitory neurons which correspond to pyramidal cells of layers II and III and to their inhibitory associated interneurons respectively; pyramidal cells are also interconnected through short and long range association fiber systems. Under such conditions, the model outputs resemble closely the experimental observations: (1) a double-bumped response to a strong and short stimulation; (2) oscillatory behavior under weak sustained stimulation conditions; (3) propagation of traveling activity waves; and (4) pacemaker activity when clusters of neurons are preferentially coupled.     

Heelstrike and the pathomechanics of osteoarthrosis: a pilot gait study

Involvement of mechanical factors in osteoarthrosis (OA) has been well documented. For OA of the human lower limb, the impulse imparted at heelstrike has been suggested as a pathogenic factor. It has also been reported that there is a large amount of variation in the level of impulse experienced by different individuals, and it is suggested that those who experience large impulses are at a greater risk of developing OA. The current study investigated gait patterns of 12 normal subjects to establish the gait determinants responsible for producing large impulses at heelstrike. The results suggest that subtle variations in the early part of the swing phase pattern are responsible for large differences in the impulse experienced at heelstrike; the usually reported gait variables mask these variations.     

Decoding emotional messages: Influence of ethnicity, sex, message type, and channel.

Studied whether sex of sender and receiver, ethnic group of sender, positivity of affect, and communication channel would influence decoding of emotional messages. 34 male and 47 female Anglo-Australian Ss viewed videotapes of male or female Australian, British, or Italian speakers, who each presented 18 content-ambiguous messages with positive, negative, or neutral affect. Ss guessed the intended affect in each message. Analyses revealed that female encoders were better decoded than male encoders for positive and negative messages on all channels, but female decoders were more accurate than males only in the audiovisual (picture and sound) condition. Positive messages were decoded least accurately, especially when the speakers were Australian men. Although Italian men in the audiovisual condition were decoded worse than other men on neutral and negative messages, in the visual (picture only) condition, Italian men were decoded as well as other men. Italian women were decoded as accurately as other women for positive and neutral messages in both the audiovisual and visual conditions. In the audio (sound only) condition, Italian speakers of both sexes were decoded less accurately than other speakers of their sex. It is suggested that Italian accents were a distractor of decoding and that Anglo-Australian Ss paid less attention because of more negative attitudes toward male Southern European immigrants. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Negative dromotropic effects of class I antiarrhythmic drugs in anisotropic ventricular muscle

OBJECTIVE: In a computer simulation study to mimic cardiac action potential, the total open time of the sodium channel at each excitation has been shown by other authors to be longer during propagation parallel (longitudinal, L) to fiber orientation than perpendicular (transverse, T) to that. If this is the case in actual cardiac tissue, the Class I antiarrhythmic drug action on conduction would be affected by their mode of sodium channel block. The present study was designed to test this hypothesis. METHODS: Effects of flecainide (F), quinidine (Q), aprindine (A) and SD3212 (S) on conduction velocity (theta), amplitude of extracellular potentials (phi e), and maximum upstroke velocity (Vmax) of action potentials were examined in isolated rabbit ventricular muscles with microscopic anisotropy. RESULTS: F (0.1-1 microM) or Q (2-10 microM), which blocks the sodium channel mainly during the activated state, caused a concentration- and frequency-dependent decrease in theta and phi e. The reduction was more prominent during L than T propagation, giving rise to a decrease in their anisotropic ratio (theta L/theta T). A (1-5 microM) or S (3-10 microM), which blocks the channel during the inactivated state, also decreased theta and phi e. However, the reduction was similar during L and T propagation, and the anisotropic ratio of theta and phi e remained unaffected. The decrease of maximum upstroke velocity (Vmax) of action potential by F or Q was greater during L than T propagation; VmaxL/VmaxT was decreased significantly. In contrast, the Vmax reduction by A(3 microM) or S (10 microM) was similar during L and T propagation. CONCLUSION: Different state-dependence of sodium channel block may underlie different negative dromotropic effects of Class I drugs in anisotropic cardiac muscle.     

Antigenic characterization of Indian isolates and vaccine strains of Newcastle disease virus

Activation of cardiac muscle is mediated by the His-Purkinje system, a discrete pathway containing fast-conducting cells (Purkinje fibers) which coordinate the spread of excitation from the atrioventricular node (AV node) to ventricular myocardium [1]. Although pathologies of this specialized conduction system are common in humans, especially among the elderly [2], their molecular bases have not been defined. Gap junctions are present at appositions between Purkinje fibers and could provide a mechanism for propagating impulses between these cells [3]. Studies of the expression of connexins - the family of proteins from which gap junctions are formed - reveal that connexin40 (Cx40) is prominent in the conduction system [4]. In order to study the role of gap junction communication in cardiac conduction, we generated mice that lack Cx40. Using electrocardiographic analysis, we show that Cx40 null mice have cardiac conduction abnormalities characteristic of first-degree atrioventricular block with associated bundle branch block. Thus, gap junctions are essential for the rapid conduction of impulses in the His-Purkinje system.     

Mechanism of action of general anesthetics. Effect on ion channel proteins or on membrane phospholipids?]

General anesthesia is defined by reversible unconsciousness, lack of response to noxious stimuli, and amnesia, induced by chemical agents. Mechanisms underlying the anesthetic effect are not known. The most prevalent belief was that anesthetic drugs acted on the lipid cell membranes, based on the correlation between oil solubility and anesthetic potency. Later, it has been proposed that anesthetic agents act on specific proteins of the cellular membrane of neurons. Voltage-gated ionic channels are inhibited by anesthetic agents, being some subtypes more sensitive. Clinical concentration of anesthetic agents inhibit or stimulate excitatory or inhibitory neurotransmitter receptors, respectively. Specific receptor agonists and antagonists modify this effect. Intercellular channels (gap junctions) are also affected by anesthetic agents through direct interaction with some of their protein subunits. Thus, anesthesia would result from combined effects on specific proteins acting on neural cell excitability as well as transmission and propagation of nerve impulses.     

Environmentally Influenced Mixed Mode Fatigue Crack Propagation of Titanium Metal Matrix Composites

Effect of humid air environments on the mixed mode fatigue crack propagation behavior of B₄C-B and BORSIC reinforced Ti-6A1-4V metal matrix composites was studied. Humid environments enhanced the mixed mode fatigue crack propagation rates in the as-received titanium matrix composites atR = 0.1. The effect was more pronounced in the transverse and 45 deg specimens. A transition in failure modes from fiber splitting in humid air to interfacial splitting in dry environments was observed at a load ratio of 0.1. The transition took place at around 100 Pa water vapor pressure, where a steep rise in fatigue crack propagation rate was noticed. AtR = 0.5, however, no fiber splitting was observed in humid air. Fatigue crack closure load measurements revealed that closure loads were higher in humid air than in dry environments. The fiber splitting is suggested as an environmentally induced crack closure effect, where plastically deformed matrix sets up stress fields (radial and mode III stresses) on the brittle boron fibers weakened by the humidity.     

Effect of myocardial fiber direction on epicardial potentials

BACKGROUND: Understanding the relations between the architecture of myocardial fibers, the spread of excitation, and the associated ECG signals is necessary for addressing the forward problem of electrocardiography, that is, predicting intracardiac and extracardiac ECGs from known intracardiac activity. So far, these relations have been studied experimentally only in small myocardial areas. In this study, we tested the hypothesis that potential distributions measured over extensive epicardial regions during paced beats reflect the direction of superficial and intramural fibers through which excitation is spreading in both the initial and later stages of ventricular excitation. We also tried to establish whether the features of the epicardial potential distribution that correlate with fiber direction vary as a function of pacing site, intramural pacing depth, and time elapsed after the stimulus. An additional purpose was to compare measured epicardial potentials with recently published numerical simulations depicting the three-dimensional spread of excitation in the heart muscle and the associated potential fields. METHODS AND RESULTS: The hearts of 18 mongrel dogs were exposed and 182 to 744 unipolar electrograms were recorded from epicardial electrode arrays (2.3 x 3.0 to 6.5 x 6.5 cm). Hearts were paced at various intramural depths through an intramural needle. The overall number of pacing sites in 18 dogs was 241. Epicardial potential distributions, electrographic waveforms, and excitation time maps were displayed, and fiber directions in the ventricular wall underlying the electrodes were determined histologically. During the early stages of ventricular excitation, the position of the epicardial maxima and minima revealed the orientation of myocardial fibers near the pacing site in all cases of epicardial and intramural pacing and in 60% of cases of endocardial or subendocardial pacing. During later stages of propagation, the rotation and expansion of the positive areas correlated with the helical spread of excitation through intramurally rotating fibers. Marked asymmetry of potential patterns probably reflected epicardial-endocardial obliqueness of intramural fibers. Multiple maxima appeared in the expanding positive areas. CONCLUSIONS: For 93% of pacing sites, results verified our hypothesis that epicardial potential patterns elicited by ventricular pacing reflect the direction of fibers through which excitation is spreading during both the initial and later stages of propagation. Epicardial potential distributions provided information on the site of origin and subsequent helical spread of excitation in an epicardial-endocardial, endocardial-epicardial, or double direction. Results were in agreement with previously published numerical simulations except for the asymmetry and fragmentation of the positive areas.     

An action test of hypotheses concerning the anal personality.

Psychoanalytic characterology posits that distinctive traits which are associated with conflicts in various impulse areas will be manifest in extreme degrees when the conflict is inadequately resolved. 48 Ss performed a hand-eye coordination task (action test) in an odorous dirty medium reminiscent of fecal matter. Poor performance of this task was taken as an index of ineffective defenses against anal impulses. It was predicted that indecisiveness and narrow intellectualism would be associated with ineffective defenses. Ss with unsuccessful action tests showed slower decision making and a selective sensitivity for anal concepts. Questionnaire study indicated that they also profess greater discomfort in areas which are characteristically troublesome for anal personalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

15Cr14Co12Mo5Ni2齿轮钢的扭转疲劳特性及裂纹扩展行为

 通过扭转疲劳试验,研究了15Cr14Co12Mo5Ni2钢的扭转疲劳断裂的裂纹扩展行为和夹杂物尺寸与扭转疲劳寿命之间的关系。得到了钢的扭转疲劳极限强度和[τ-N]曲线,15Cr14Co12Mo5Ni2钢的扭转疲劳极限强度为350 MPa,扭转疲劳寿命分散度较大。通过断口观察,发现15Cr14Co12Mo5Ni2钢的疲劳破坏模式以表面破坏和近表面破坏为主,主要由氧化物夹杂引起。通过计算应力强度因子[ΔK]和裂纹扩展门槛值[ΔKth]分析15Cr14Co12Mo5Ni2钢的疲劳裂纹扩展的断裂力学条件,试验钢在断裂过程中受载荷情况为,II型载荷—I型载荷—II型载荷—I＋II型载荷,分别对应起裂源区、纤维区、疲劳裂纹扩展区和瞬断区;当有大裂纹产生时,则不会产生纤维区,受载荷情况则为：II型载荷—I＋II型载荷。通过公式推导和数据拟合得到夹杂物尺寸和15Cr14Co12Mo5Ni2钢扭转疲劳寿命的关系,发现随着夹杂物尺寸减小,钢的[τ-N]曲线向高寿命区移动。当引起裂纹萌生的夹杂物尺寸小于5 μm时,在350 MPa应力下,15Cr14Co12Mo5Ni2钢的扭转疲劳寿命超过107循环周次。     

Directed forgetting: Comparing pictures and words.

The authors investigated directed forgetting as a function of the stimulus type (picture, word) presented at study and test. In an item-method directed forgetting task, study items were presented 1 at a time, each followed with equal probability by an instruction to remember or forget. Participants exhibited greater yes–no recognition of remember than forget items for each of the 4 study–test conditions (picture–picture, picture–word, word–word, word–picture). However, this difference was significantly smaller when pictures were studied than when words were studied. This finding demonstrates that the magnitude of the directed forgetting effect can be reduced by high item memorability, such as when the picture superiority effect is operating. This suggests caution in using pictures at study when the goal of an experiment is to examine potential group differences in the magnitude of the directed forgetting effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stability analysis of the FitzHugh-Nagumo differential equations driven by impulses: applied to the electrical firing of magnocellular neurons

A stability analysis is carried out for a mathematical model which describes the electrical firing of a single vasopressin neuron. The model used in a FitzHugh-Nagumo-type system which is driven by impulses. The analysis is based on recent developments in the stability theory of impulsive differential equations. Conditions are derived under which the system of differential equations is stable at two of its equilibrium points. Biologically this bistability represents the cell alternating between periods of electrical activity and silence. The conditions for stability are specified in terms of the amplitude and frequency of the impulses perturbing the system. Both stochastic and deterministic impulses are considered.     

Studies on local contractile characteristics in normal and ischemic myocardium and the role of collateral circulation in restoration of contraction abnormalities during ischemia (author''s transl)

The presence of supernormal excitation was confirmed repeatedly in all 10 cases following cardiac surgery. By the stimulation of minimum subthreshold impulses capable of originating ventricular responses, the supernormal excitation was limited only at the descending limb of T wave. The duration lasted only 0.02 sec at the minimum subthreshold stimuli. But the higher subthreshold stimuli produced the longer duration of supernormal excitation phase. The duration of the excitation phase prolonged towards the following R wave, hardly extending towards the preceding R wave, with the increase of subthreshold stimuli.