Subthreshold dynamics in periodically stimulated squid giant axons.
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Biomedical subjects
Publications and source records attributed to L Glass.
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INTRODUCTION: Alternation of atrial cycle length and AV nodal conduction time (NCT) is often observed during AV reentrant tachycardia. Both AV nodal dual pathway and rate-dependent function have been postulated to be involved in this phenomenon. This study was designed to determine the respective role of these two mechanisms in the alternation observed in an in vitro model of orthodromic AV reentrant tachycardia. METHODS AND RESULTS: The tachycardia was produced by detecting each His-bundle activation and stimulating the atrium after a retrograde delay, thereby simulating retrograde pathway conduction, in six isolated rabbit heart preparations. After a 5-minute stabilization period at a fast rate, the retrograde delay was decremented by 2 msec every minute until nodal blocks occurred. We observed a sequential alternation of the cycle length and NCT in four preparations in the short retrograde delay range. The magnitude of the alternation gradually increased as the retrograde delay was decreased and reached 4.6 +/- 0.5 msec during 1:1 conduction. The alternation increased further just prior to termination of the tachycardia by an AV nodal block. None of the preparations showed discontinuous AV nodal recovery curves. Moreover, an electrode positioned over the endocardial surface of the node showed that the alternation developed distally to the nodal inputs, which are believed to constitute a major component of dual pathways. A mathematical model predicted the alternation from known characteristics of rate-dependent nodal functional properties. CONCLUSIONS: NCT and cycle length alternation can arise during orthodromic AV reentrant tachycardia when the retrograde delay is sufficiently short. The characteristics of the alternation, presence of continuous recovery curves, intranodal location of the alternation, and mathematical modeling suggest that the alternation is predictable from the known functional properties of the AV node without postulating dual pathway physiology.
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A theoretical model, formulated as a finite difference equation is proposed for rate-dependent conduction properties of the atrioventricular (AV) node. The AV nodal conduction time, which is defined as the time interval from the atrial activation to the activation of the bundle of His, depends on the history of activation of the node. The theoretical model, which incorporates physiological concepts of recovery, facilitation and fatigue, accurately predicts a variety of experimentally observed complex rhythms of nodal conduction. In particular, alternans rhythms, in which there is an alternation in conduction time from beat to beat, are associated with period-doubling bifurcations in the theoretical model.
In spontaneously beating chick heart cell aggregates, sustained periodic stimulation at a rate faster than the intrinsic frequency is generally followed by a transient slowing of the automatic rhythm called "overdrive suppression." We characterize the qualitative aspects of overdrive suppression using three sets of experimental protocols: 1) stimulation at a fixed frequency with various numbers of stimuli, 2) stimulation at different frequencies, 3) stimulation with different intensities. We develop a mathematical model based on a system of nonlinear ordinary differential equations to account for the experimental observations. The main idea of the model is that overdrive suppression arises as a result of a hyperpolarizing current that is induced by action potentials. This work shows that the frequency of action potentials is the major determinant of overdrive suppression. Consequently, during periodic pacing of spontaneous oscillators at different rates, the fastest frequency where 1:1 entrainment can be maintained is associated with maximal overdrive suppression. This type of model is complementary to the development of a rigorous ionic model and can help provide insight into the physiological mechanisms of overdrive suppression.
Thirteen healthy subjects were asked to maintain a constant index finger position in Experiment 1 or a constant eye position in Experiment 2 using visual feedback. The finger or eye position along with a stationary baseline target was displayed on an oscilloscope placed in front of the subject. Experiments 1 and 2 were carried out under sixteen combinations of delay and amplification of displacement on the screen (i.e., gain). In Experiment 1, increasing the gain in the visual feedback decreased the Root Mean Square (RMS) errors while increasing the delay increased these errors. An interaction between gains and delays was also observed in Experiment 1. In Experiment 2, the RMS errors were systematically higher than those recorded in Experiment 1 for the finger. No systematic pattern was recognized across all conditions of gains and delays for eye movements in Experiment 2. This study clearly illustrates differences in dynamics of motor control systems regulating eye and finger positions, respectively.
Most social work caseloads include some people who are deaf or hard-of-hearing, yet few social workers are attuned to the different and subtle ways in which hearing impairment can affect identity and relationships. People with hearing impairment make many self-defining choices--of communication method; language; and social, cultural, and political allegiance. Using information collected during a three-year research study of people with acquired hearing loss, this article defines and describes the complex and interrelated dimensions involved in assessing and serving people who are deaf or hearing impaired.
Neuroanatomical abnormalities have been linked to maternal cocaine abuse since Chasnoff et al's report of cerebral infarction in a single full-term offspring of a cocaine-abusing mother. Neurosonography was performed on 18 full-term offspring of cocaine-abusing mothers and 19 age-matched controls to look for possible abnormalities. There were no cases of infarction or intraparenchymal or intraventricular hemorrhage. There were, however, 6 patients with abnormalities among the cocaine-abusing group: 5 patients with unilateral or bilateral germinal matrix cysts and 3 patients with subtle cystic or predominantly cystic areas in watershed zones consistent with periventricular leukomalacia.
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Plasma selenium of infants fed proprietary formula was significantly less than that in infants fed human milk. Addition of selenite to the formula (0.253 mumol Se/L) increased plasma selenium and activities of glutathione peroxidase (GPx) and total peroxidase (Px). However, erythrocyte selenium decreased significantly during the 12-wk study in infants receiving human milk or formula with or without supplemental selenite. Infants fed human milk from women receiving 0 or 200 micrograms supplemental selenium as selenomethionine or selenium-enriched yeast had plasma selenium that paralleled changes in their selenium intake. Plasma GPx and Px activities were unrelated to human milk selenium intake. Milk from women given either selenium supplement prevented the decline in infant erythrocyte selenium. Results of these studies suggest that the method of feeding modifies the infant's apparent selenium status and that the molecular form of selenium provided and/or its interaction with other milk constituents are determinants of infant selenium status.
The impact of providing selenomethionine (2.7 mumol Se) or selenium-enriched yeast (2.9 mumol Se) on the selenium status of lactating and nonlactating women with customary intakes of approximately 1.3 mumol Se/d was studied. Plasma selenium declined in unsupplemented lactating women but not in nonlactating women. Selenomethionine increased plasma selenium in both lactating and nonlactating women whereas selenium-enriched yeast increased plasma selenium only in nonlactating women. Erythrocyte selenium concentration was not significantly modified by lactation. Plasma glutathione peroxidase (GPx) activity decreased with duration of lactation in unsupplemented women and selenomethionine or selenium-enriched yeast supplementation prevented the decline. Milk selenium declined markedly for 20 wk after parturition in unsupplemented women. Selenomethionine significantly increased milk selenium concentrations whereas selenium-enriched yeast prevented a decline. These results clearly show that the source of selenium provided to lactating women can significantly influence selected indexes of selenium status, including milk selenium concentration.
The role of genital mycoplasmas in the pathogenesis of neonatal infection is incompletely understood. We performed nasopharyngeal, blood and cerebrospinal fluid (CSF) cultures for Mycoplasma hominis and Ureaplasma urealyticum in 69 neonates who underwent a diagnostic workup for suspected sepsis. The mean gestational age was 35.9 weeks (range, 25 to 42 weeks) with a mean birth weight of 2386 g (range, 652 to 4420 g). Twenty-seven infants (39.1%) had positive nasopharyngeal cultures; 6 were positive for M. hominis, 10 for U. urealyticum and 11 for both organisms. Seven (26%) of these 27 patients developed chronic lung disease compared with 2 (4.7%) infants in the non-colonized group. Nine infants had positive CSF cultures for M. hominis and one infant had a positive CSF culture for U. urealyticum. All blood cultures were sterile. One of the infants with a positive CSF culture for M. hominis had clinical evidence of systemic infection. All of the infants were treated with antibiotic agents that were not active against mycoplasmas. These data indicate that genital mycoplasmas can be found commonly in the CSF and nasopharynx of infants with suspected sepsis. Their etiologic role in the causation of infection and chronic lung disease, however, remains unclear.
A variety of mathematical methods have been developed to characterize complex rhythms that are observed in physiological systems. These methods include classical techniques such as the mean, standard deviation, and power spectrum, as well as newer methods suggested by nonlinear dynamics including the dimension, Lyapunov number, and entropy. This paper reviews the various ways in which these measures have been applied to analyze physiological dynamics with emphasis on the potential advantages and pitfalls of the various approaches. We conclude that these methods may be useful to help characterize complex time series, but only rarely is it possible to use these methods to establish deterministic chaos in a given time series.
In a previous study (Lewis et al., 1990), the response of the respiratory rhythm to a perturbing stimulus was investigated using two different stimulus protocols: phase resetting and fixed-delay stimulation. The first protocol consists of measuring the effects of perturbing an oscillator at different phases of the cycle on the duration of the perturbed cycle. The resulting phase response curves (PRCs) can be used to characterize the properties of the oscillator (Winfree, 1980). A second protocol, fixed-delay stimulation, involves perturbing an oscillator at a fixed latency from the onset of the cycle, repeated every n-th cycle. If a single stimulus produces an effect that lasts longer than a single cycle, complicated responses can be expected from fixed-delay stimulation (Lewis et al., 1987). A simple three-phase model for respiratory rhythm generation based on a hypothesis by Richter and coworkers (1982, 1983, 1986) was investigated in the context of these experimental studies. Phase resetting and fixed-delay stimulation protocols were simulated in the model. PRCs of the model resemble those obtained experimentally: a phase-dependent prolongation or shortening of the inspiratory phase depending on the stimulus magnitude, and a slight prolongation of the expiratory phase. Stimuli delivered to the model repetitively during successive inspiratory periods at a fixed-delay produced various combinations of shortened and prolonged cycles, similar to those observed in the experiments. However, the marked increases in cycle duration observed in the experiments during, as well as after, stimulation were not evident in the model. These comparisons suggest that (1) PRCs may not be an adequate way to evaluate certain models of rhythmogenesis, and (2) to improve the present simplified formulation of the three-phase model of the respiratory oscillator, time-varying stimulus dependent effects should be incorporated.