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PubMed2005

Perceptual thresholds and electrode impedance in three retinal prosthesis subjects.

Three test subjects blind from retinitis pigmentosa were implanted with retinal prostheses as part of a FDA-approved clinical trial. The implant consisted of an extraocular unit that contained electronics for wireless data, power, and generation of stimulus current, and an intraocular unit that consisted of 16 platinum stimulating electrodes arranged in a 4 x 4 pattern within a silicone rubber substrate. The array was held to the retina by a small tack. The stimulator was connected to the array by a multiwire cable and was controlled by a computer based external system that allowed precise control over each electrode. Perception thresholds and electrode impedance were obtained on each electrode from the subjects over several months of testing. The electrode distance from the retina was determined from optical coherence tomography imaging of the array and retina. Across all subjects, average thresholds ranged from 24-702 microA (1-ms pulse). The data show that proximity to the retina played a role in determining the threshold and impedance, but only for electrodes that were greater than 0.5 mm from the retina.

Blindness↗

PubMed1977

Effects of local anesthetics on tactile sensitivity thresholds for cutaneous and mucous membranes.

New, reliable, and precise methods for measuring absolute pressure sensitivity in mucous membranes and on intact skin are described. Studies were conducted to determine how local anesthetics (phenol and sodium phenolate and Benzocaine) affect tactile sensitivity thresholds in the oropharynx and on the intact skin of the volar surface of the forearms, ankles, knees, elbows, and dorsum of the hands. Gargling and expectorating a solution containing phenol had a significantly greater anesthetic effect on the mucous membranes of the oropharynx than spraying and swallowing, which, in turn, had a greater effect than drinking the solution. Compared with ethanol and petroleum jelly (Vaseline), the topical application of Benzocaine (0, .5, 1, 3, and 5% solutions in 100% ethanol) significantly increased the tactile sensory thresholds on the volar surface of the forearm. A highly significant loss of tactual sensitivity of the oropharynx was demonstrated in smokers.

Adolescent↗

PubMed2000

The strength-duration curve and its importance in pacing efficiency: a study of 325 pacing leads in 229 patients.

Pacemaker battery life is dependent on programmable parameters, principally pulse amplitude and pulse duration. High factory default settings cause excessive current drain. The strength-duration curve relates pacing threshold to pulse duration. The most energy efficient pacing occurs at chronaxie, a value of pulse duration derived from the curve. Strength-duration curves were calculated for 325 acutely implanted pacing leads. Chronaxie and rheobase were compared for atrial and ventricular leads. Chronaxie was compared with actual programmed pulse duration. There were 101 atrial and 224 ventricular leads, all passive fixation. The curve fit was good, (mean error +/- SD) 0.024 +/- 0.06 V for atrial curves and 0.008 +/- 0.034 V for ventricular curves. Mean (+/- SD) atrial and ventricular chronaxies were 0.24 +/- 0.07 ms and 0.25 +/- 0.07 ms, respectively. A "Z" value of 1.4 indicated that chronaxies might have been from the same population. Mean (+/- SD) atrial and ventricular rheobases were 0.51 +/- 0.2 V and 0.35 +/- 0.13 V, respectively. A "Z" value of 7.1 (P < 0.001) suggested atrial and ventricular rheobases were from differing populations. All patients had factory default pulse durations of 0.45 ms or 0.5 ms, exceeding acute chronaxie by a factor of two, thus, demonstrating suboptimal pacing. We conclude that understanding the strength-duration curve is critical. Sensible programming of other pacing functions optimizes longevity. Battery drain is reduced by programming pulse duration to chronaxie with a doubling of voltage threshold at this point to achieve a safety margin. Further study of chronaxie drift with time is required.

Adult↗

PubMed2002

Cardiopulmonary resuscitation in the mouse.

We sought to develop a model of cardiac arrest and resuscitation on mice that would be comparable to that of large mammals and would allow for more fundamental investigations on cardiopulmonary arrest and cardiac resuscitation. A model of cardiopulmonary resuscitation previously developed by our group on rats was adapted to anesthetized, mechanically ventilated adult male Institute of Cancer Research mice that weighed 46 +/- 3 g. The trachea was intubated through the mouth, and end-tidal PCO(2) (PET(CO(2))) was measured with a microcapnometer. Catheters were advanced into the aorta and into the right atrium, and coronary perfusion pressure (CPP) was computed. A 1.5-mA alternating current was delivered to the right ventricular endocardium, which produced ventricular fibrillation or a pulseless rhythm. Precordial compression was begun 4 min later. Ten sequential studies were performed, during which five animals were successfully resuscitated and five failed resuscitation efforts. Successful resuscitation was contingent on the restoration of threshold levels of CPP and PET(CO(2)) during chest compression. As in rats, swine, and human patients, threshold levels of mean aortic pressure, CPP, and PET(CO(2)) were critical determinates of resuscitability in this murine model of threshold level of cardiac arrest and resuscitation.

Acid-Base Equilibrium↗

PubMed1988

Extracellular field required for excitation in three-dimensional anisotropic canine myocardium.

It is not known how well potential gradient, current density, and energy correlate with excitation by extracellular stimulation in the in situ heart. Additionally, the influence of fiber orientation and stimulus polarity on the extracellular thresholds for stimulation expressed in terms of these factors has not been assessed. To answer these questions for myocardium in electrical diastole, extracellular excitation thresholds were determined from measurements of stimulus potentials and activation patterns recorded from 120 transmural electrodes in a 35 X 20 X 5-mm region of the right ventricular outflow tract in six open-chest dogs. Extracellular potential gradients, current densities, energies, and their components longitudinal and transverse to the local fiber orientation at each recording site were calculated from the stimulus potentials produced by 3-msec constant-current stimuli. The resulting values in regions directly excited by the stimulus field were compared with the values in regions not directly excited but activated by the spread of wavefronts conducting away from the directly excited region. Magnitudes of 3.66 mA/cm2 for current density, 9.7 microJ/cm3 for energy, and 804 mV/cm for potential gradient yielded minimum misclassifications of 8%, 13%, and 17%, respectively, of sites directly and not directly excited. A linear bivariate combination of the longitudinal (l) and transverse (t) components of the potential gradient yielded 7% misclassification (threshold ratio t/l of 2.88), and linear combination of corresponding current density components yielded 8% misclassification (threshold ratio t/l of 1.04). Anodal and cathodal thresholds were not significantly different (p = 0.39). Potential gradient, current density, and energy strength-duration curves were constructed for pulse durations (D) of 0.2-20 msec. The best fit hyperbolic curve for current density magnitude (Jm) was Jm = 3.97/D + 3.15, where Jm is in mA/cm2, and D is in msec. Thus, for stimulation during electrical diastole 1) both current density magnitude and longitudinal and transverse components of the potential gradient are closely correlated with excitation, 2) the extracellular potential gradient along cardiac cells has a lower threshold than across cells, while current density thresholds along and across cells are similar, 3) anodal and cathodal thresholds are approximately equal for stimuli greater than or equal to 5 mA, and 4) the extracellular potential gradient, current density, and energy excitation thresholds can be expressed by strength-duration equations.

Action Potentials↗

PubMed1989

Visual display lowers detection threshold of angular, but not linear, whole-body motion stimuli.

The influence of a visual display, fixed relative to the subject, on thresholds for detection (at 75% correct) of discrete Y-axis linear movements and of discrete Z-axis angular movements, was determined in a group of 12 subjects. Both the linear and the angular, whole-body, motion stimuli had a cosine bell velocity trajectory with a duration of 2.6 s. Thresholds for the detection of the linear motion stimuli in darkness were not significantly different from those obtained when either a simple LED display or an instrument dial were illuminated; the mean threshold was 0.039 m.s-2. None of the subjects reported apparent movement of the visual display. In contrast, the presence of either visual display lowered angular motion thresholds on average by a factor of 2.7 from that obtained in darkness (1.61 degrees.s-1). All subjects reported apparent movement of the visual display, an oculogyral illusion, at stimulus intensities close to the dark threshold. These findings imply that otolithic afferents, unlike those from the semicircular canals, do not interact with neural centres mediating visual localization.

Acceleration↗

PubMed1994

Picrotoxin and pentylene tetrazole induced seizure activity in pyridoxine-deficient rats.

Computerized electroencephalography and thalamic ventro-posterior lateral (VPL) unit activities were recorded from pyridoxine-deficient and pair-fed pyridoxine-supplemented adult male rats. Pyridoxine-deficient animals exhibited slow electroencephalograms (EEG) represented by the dominance of delta activity and reduced seizure thresholds to local (VPL) application of either picrotoxin or pentylene tetrazole. Frequency and amplitude of thalamic VPL unit activity were significantly reduced in pyridoxine-deficient rats as compared to pyridoxine-supplemented controls. Pyridoxine-deficient rats exhibited irregular unit activity with frequent bursts and electrosilent periods in response to local (VPL) picrotoxin or pentylene tetrazole microinjections. They also exhibited severe seizure discharge activity of prolonged duration at any given dose of either picrotoxin or pentylene tetrazole. This was represented by significantly increased burst frequency, burst duration and reduced seizure latencies. Unit activity was transformed into burst discharge activity with intermittent electrosilent zones during picrotoxin or pentylene tetrazole epileptogenesis. Cerebral gamma aminobutyric acid (GABA) level was reduced and glutamate concentration increased in pyridoxine-deficient rats when compared with pyridoxine-supplemented controls. Local (VPL) microinjection of GABA or pyridoxine induced neuronal recovery in both convulsant-treated normal and pyridoxine-deficient rats. Neuronal recovery was however delayed in pyridoxine-deficient rats. Neuronal recovery was associated with a significant increase in EEG background frequency and reduction in delta frequencies in the EEG records of both normal and pyridoxine-deficient rats. Reduced seizure threshold and delayed neuronal recovery are related to the significantly reduced brain regional GABA and elevated glutamate levels in pyridoxine-deficient rats.

Animals↗

PubMed1990

Postnatal development of the T calcium current in cat thalamocortical cells.

The burst firing of thalamic cells in the adult cat is mainly controlled by a voltage-dependent membrane current that has recently been characterized as being similar to the low voltage-activated (i.e. low threshold), T-type, Ca2+ current originally described in sensory neurons. In those neurons so far studied, as well as in skeletal muscle, the low threshold Ca2+ current has been shown to decrease in amplitude or even disappear during embryogenesis or the first few weeks of postnatal life. We have now investigated the in vivo postnatal development of the low threshold Ca2+ current present in thalamocortical cells of the dorsal lateral geniculate nucleus of cats aged four to 100 days. The results show that the amplitude of the low threshold Ca2+ current triples from 0.5 nA in the first few days after birth to over 1.5 nA in the adult. However, this increase in amplitude is not accompanied by any change in its inactivation and activation properties, its latency to peak and the time dependence of inactivation removal. Because of these similarities during development and in adulthood it is likely that a major role of the low threshold Ca2+ current during neuronal development is the generation of oscillatory activities similar to those observed in adult thalamocortical cells.

Animals↗

PubMed1990

The ototoxic mechanism of cisplatin.

The ototoxic mechanism of cisplatin was investigated. Potentiation of cisplatin ototoxicity by furosemide and amino-oxyacetic acid (AOAA) was observed. Substantial hearing loss in cisplatin-deafened animals was accompanied by normal values of the endocochlear potential and a reduction in the sensitivity of the 2f1-f2 distortion products. The loss in dB of the sensitivity of the distortion products correlated extremely well with the loss of the neural sensitivity in dB. There was also a relationship between the fractional reduction of the low frequency (1000 Hz) microphonic potential and hearing loss in dB. Iontophoresis of cisplatin into scala media resulting in the immediate loss of neural thresholds at the site of iontophoresis. It is concluded that cisplatin caused the hearing loss by blocking OHC transduction channels.

Aminooxyacetic Acid↗

PubMed2002

Can we determine a threshold level for allergenic foods by statistical analysis of published data in the literature?

BACKGROUND: The aim of this paper was to investigate whether a statistical model could be developed to estimate a "threshold" dose for foods eliciting allergic reactions in susceptible patients. The threshold dose is defined to be one that elicits allergic reactions in a given (small) proportion of susceptible patients, using data from published studies. METHODS: Based on data available from the literature, we developed a statistical model using the actual allergen content in the four foods, where data for allergen content are available (peanut, soy, egg, milk). RESULTS: The model demonstrated that the threshold doses giving a reaction of one in a million in susceptible patients were within the same order of magnitude for egg, milk and soy, but were an order of magnitude lower for peanut flour: 0.005 mg of cow's milk, 0.002 mg of fresh hen's egg, 0.0007 mg of peanut, or 0.0013 mg of soy flour. CONCLUSIONS: Although several assumptions were made in creating this statistical model, we demonstrated that the previously published differences in threshold doses for various foods can be largely eliminated by comparing actual allergen content; this may therefore serve as a model for further studies.

Allergens↗

PubMed2002

Influence of aging on electrogustometry thresholds.

Taste thresholds were measured using electrogustometry by the same researcher at three pairs of sites in the mouth (soft palate, tongue tip and tongue base) in both smokers and non-smokers (n = 461; age range 15-94 years). Comparison of the results by decades showed that the threshold increased significantly with age, starting at age 60 for areas innervated by the chorda tympani and glossopharyngeal nerves and at age 70 for areas innervated by the greater petrosal nerve. For the older teenage subjects, females had significantly lower thresholds than males and thresholds for women tended to be lower than those for men at all sites examined. Thresholds for the two sides of the tongue were within approximately 6 dB of each other. Thresholds on the soft palate were consistently higher than those on the tongue tip and tongue base. Little difference was detected between thresholds on the tongue tip and those on the tongue base except in older teenage subjects, in whom thresholds on the tongue tip were significantly lower than those on the tongue base. Male smokers in their 30s and 40s had significantly lower thresholds on the soft palate than non-smokers in this age group.

Adolescent↗

PubMed2003

Myocardial contractile function during postischemic low-flow reperfusion: critical thresholds of NADH and O2 delivery.

The degree of myocardial oxygen delivery (Do2) that is necessary to reestablish functional contractile activity after short-term global ischemia in heart is not known. To determine the relationship between Do2 and recovery of contractile and metabolic functions, we used tissue NADH fluorometric changes to characterize adequacy of reperfusion flow. Isolated perfused rat hearts were subjected to global ischemia and were reperfused at variable flow rates that ranged from 1 to 100% of baseline flow. Myocardial function and tissue NADH changes were continuously measured. NADH fluorescence rapidly increased and plateaued during ischemia. A strong inverse logarithmic correlation between NADH fluorescence and reperfusion Do2 was demonstrated (r = -0.952). Left ventricular function (rate-pressure product) was inversely related to NADH fluorescence at reperfusion flows from 25 to 100% of baseline (r = -0.922) but not at lower reperfusion flow levels. An apparent reperfusion threshold of 25% of baseline Do2 was necessary to resume contractile function. At very low reperfusion flows (1% of baseline), another threshold flow was identified at which NADH levels increased beyond that observed during global ischemia (3.4 +/- 3.0%, means +/- SE, n = 9), which suggests further reduction of the cellular redox state. This NADH increase at 1% of baseline reperfusion flow was blocked by removing glucose from the perfusate. NADH fluorescence is a sensitive indicator of myocardial cellular oxygen utilization over a wide range of reperfusion Do2 values. Although oxygen is utilized at very low flow rates, as indicated by changes in NADH, a critical threshold of approximately 25% of baseline Do2 is necessary to restore contractile function after short-term global ischemia.

Animals↗

PubMed1987

Membrane potential and vascular smooth muscle sensitivity. A minireview.

A review of research on the relationship between the regulation of cellular sensitivity to drugs and transmitters and membrane potential is presented, with an emphasis on experiments with the rabbit saphenous artery. Chronic depression of the adrenergic innervation to the saphenous artery induces an adaptive and nonspecific increase in sensitivity which appears with a delay of 3 days. Coincident with the supersensitivity, the smooth muscle cells undergo a partial depolarization which brings the resting potential closer to the threshold potential for contraction. The evidence is that the depolarization is due to the loss of electrogenic Na+, K+ pumping and is the primary factor responsible for the supersensitivity.

Animals↗

PubMed1987

Relationship between canine transthoracic impedance and defibrillation threshold. Evidence for current-based defibrillation.

The electrical parameter used to define defibrillation strength is energy. Peak current, however, may more accurately reflect the field quantities (i.e., electric field strength and current density) that mediate defibrillation and therefore should be a better clinical descriptor of threshold than energy. Though transthoracic impedance is a major determinant of energy-based threshold and is sensitive to operator-dependent changes in impedance (electrode-subject interface), an ideal threshold descriptor should be invariant with respect to these changes in impedance. We therefore compared the relative invariance of energy- and current-based thresholds when transthoracic impedance was altered by one of two methods: (a) change in electrode size (protocol A) or (b) change in electrode force (protocol B). In protocol A, impedance was altered in each dog by a mean of 95%. Energy thresholds determined at both low and high impedance were 44 +/- 21 J (mean +/- SD) and 105 +/- 35 J, respectively, P less than 0.0001. In contrast, peak current (A) thresholds were independent of transthoracic impedance, 22 +/- 5 A (low impedance) vs. 24 +/- 6 A (high impedance), P = NS. Energy and current thresholds showed a similar relationship for animals tested in protocol B. Therefore, current-based thresholds, in contrast to energy thresholds are independent of operator-dependent variables of transthoracic impedance and are invariant for a given animal. These results suggest that redefining defibrillation threshold in terms of peak current rather than energy provides a superior method of defibrillation.

Animals↗

PubMed1998

Effect of inspiratory muscle training with an intermediate load on inspiratory power output in COPD.

There is very little information about the effect of inspiratory muscle training on inspiratory flow (V'I) and thus on power output (PO) in patients with chronic obstructive pulmonary disease (COPD). In this study we aimed to evaluate the changes induced by training on the determinants of PO. Thirty one patients with severe COPD were randomly divided into: Group 1, trained with 30% maximal inspiratory pressure (PI,max); Group 2, with 10% PI,max; and Group 3 also trained with 30% PI,max, but the breathing pattern was evaluated while performing the training manoeuvres along inspiratory muscle training (IMT). All groups used a threshold device for 10 weeks. The PO for each of the loads during an incremental threshold test was evaluated prior to and after training. Maximal PO (POmax) increased in all groups, but the increment was higher in groups trained with 30% PI,max (p<0.005), mainly due to an increase in V'I. Group 3 showed a progressive increase in V'I (p<0.001) during the training manoeuvres in spite of an increase in load along IMT. In addition, the load after IMT was overcome with a shorter inspiratory time (tI) (p<0.02), a smaller tI/total duration of the respiratory cycle (t(tot)), (p<0.001) with no change in tidal volume or t(tot). The increment in POmax in this group correlated with the V'I generated while training (r=0.85; p<0.0001). We conclude that in patients with chronic obstructive pulmonary disease, the use of an intermediate threshold load for training improves power output mainly by increasing inspiratory flow, an effect consistent with an increase in shortening velocity of inspiratory muscles.

Aged↗

PubMed1977

Taste acuity of the human palate. I. Studies with electrogustometry and taste solutions on young adults.

The purposes of the study were to determine whether or not taste perception was present in the area which would have been covered by the base plate of a full upper denture and, if taste perception was present there, to compare its strength to that of the remainder of the soft palate and of the apex and base of the tongue. The taste acuity of 32 dental students was measured at the apex and base of the tongue and on the hard and soft palate using two methods, an electric current and sweet, salty, sour and bitter test solutions, the latter in order to determine whether or not there exist differences in the perception of the different taste modalities in these areas. No taste perception could be demonstrated on the hard palate except in the region close to the border between the hard and soft palate, where the threshold values were very high compared with those for the soft palate immediately behind this border and for the tongue. The inter-individual range of the threshold values for the soft palate was very large. Further studies on the taste acuity of the human palate and its role in the total perception of taste are indicated.

Adult↗

PubMed2000

Seizure threshold in electroconvulsive therapy: III. A long-term study.

There has been a dearth of long-term studies investigating the seizure-threshold changes in patients receiving electroconvulsive therapy (ECT). This study aimed to determine changes in seizure threshold over acute, continuation, and maintenance ECT (Phases I, II, and III). Twenty schizophrenic patients were estimated to have a seizure threshold by the dose-titration method. All patients had a rise in seizure threshold at the end of Phase I with 185 +/- 196 per cent increments. Ten patients had a further threshold-increase at the sixth month (Phase II, n = 20), and four at the twelfth month (Phase III, n = 14). The overall threshold-increases of Phases II and III were 370 +/- 342 per cent and 416 +/- 427 per cent, respectively. Seizure-threshold increases were robust during acute ECT, and tended to reach a plateau over the continuation and maintenance phases.

Adolescent↗

PubMed1998

Intracellular Ca2+ thresholds that determine survival or death of energy-deprived cells.

Increase of intracellular ionized or free Ca2+ is thought to play a central role in cell death due to ATP depletion. However, concurrently operative mechanisms of injury that do not require intracellular Ca2+ increases have made it difficult to test this hypothesis or to determine the concentrations at which intracellular Ca2+ becomes lethal. The predominant Ca2+-independent mechanism of injury during ATP depletion involves the loss of cellular glycine. This type of damage can be fully inhibited by adding the amino acid exogenously. Using glycine to suppress Ca2+-independent plasma membrane damage, we have examined the effect of intracellular Ca2+ elevations on cell viability during ATP depletion. Madin-Darby canine kidney (MDCK) cells were depleted of ATP by incubation with a mitochondrial uncoupler in glucose-free medium. Free Ca2+ concentration in the medium was varied between 26 nmol/L and 1.25 mmol/L in the presence of a Ca2+ ionophore. Measurements with the Ca2+ probes fura-2, furaptra, and fura-2FF showed that intracellular Ca2+ was clamped at extracellular levels under these conditions. Cell survival during ATP depletion was indicated by viable cells recovered 24 hours later. The results show that ATP-depleted cells can sustain high levels of intracellular Ca2+ (100 micromol/L) for prolonged periods and remain viable if plasma membrane damage is prevented by glycine. Cell death was observed only when intracellular free Ca2+ was allowed to increase beyond 100 micromol/L, and this was associated with dramatic nuclear alterations: chromatin condensation, loss of nuclear lamins, and breakdown of DNA into large 50- to 150-kb fragments. Our studies demonstrate unexpectedly high resistance of cells to calcium cytotoxicity if glycine that is lost during ATP depletion is restored. In addition, they provide insights into novel mechanisms of nuclear disintegration and DNA damage that are triggered when the high thresholds of intracellular Ca2+ required for cell death are exceeded.

Adenosine Triphosphate↗