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Suppression of cutaneous reflexes by a conditioning pulse during human walking.

There are two ways in which responses to successive unexpected stimuli are attenuated, namely through habituation and conditioning. For the latter, it suffices that the unexpected stimulus is preceded by another just perceivable stimulus. In spinal cord reflexes this is termed conditioning, while in brainstem reflexes this is usually referred to as prepulse inhibition. Cutaneous reflexes in Tibialis Anterior (TA) are particularly strong during gait and they are thought to involve a transcortical loop. Can these reflexes be suppressed by giving a brief pulse prior to a reflex-evoking pulse given to the same nerve? To examine this question, electromyographic signals were recorded in healthy humans during walking. Sural nerve stimulation (train of five pulses (1 ms duration)) at 200 Hz were applied at two times perception threshold during different phases of the step cycle. The preceding pulse (single pulse of 1 ms at same intensity) was applied to the same nerve 150 ms before the reflex-evoking pulse train. Conditioning stimulation with a single pulse lowered significantly the following reflex response in the ipsilateral TA but much less in other muscles such as biceps femoris. The preceding pulse did not disturb the phase-dependent modulation or the typical reflex reversal. The finding that TA is selectively involved indicates that the suppressing mechanism may involve the motor cortex, which is known to be involved in the control of TA. The conditioning pulse did not cause a reduction in background activity. Therefore, the suppression of the reflex responses points to a premotoneuronal source such as presynaptic inhibition.

Adult↗

Temporally patterned sound pulse trains affect intensity and frequency sensitivity of inferior collicular neurons of the big brown bat, Eptesicus fuscus.

This study examined the effect of temporally patterned pulse trains on intensity and frequency sensitivity of inferior collicular neurons of the big brown bat, Eptesicus fuscus. Intensity sensitivity of inferior collicular neurons was expressed by the dynamic range and slope of rate-intensity functions. Inferior collicular neurons with non-monotonic rate-intensity functions have smaller dynamic ranges and larger slopes than neurons with monotonic or saturated rate-intensity functions. Intensity sensitivity of all inferior collicular neurons improved by increasing the number of non-monotonic rate-intensity functions when the pulse repetition rate of pulse trains increased from 10 to 30 pulses per second. Intensity sensitivity of 43% inferior collicular neurons further improved when the pulse repetition rate of pulse trains increased still from 30 to 90 pulses per second. Frequency sensitivity of inferior collicular neurons was expressed by the Q10, Q20, and Q30 values of threshold frequency tuning curves and bandwidths of isointensity frequency tuning curves. Threshold frequency tuning curves of all inferior collicular neurons were V-shape and mirror-images of their counterpart isointensity frequency tuning curves. The Q10, Q20, and Q30 values of threshold frequency tuning curves of all inferior collicular neurons progressively increased and bandwidths of isointensity frequency tuning curves decreased with increasing pulse repetition rate in temporally patterned pulse trains. Biological relevance of these findings to bat echolocation is discussed.

Animals↗

Use of pulse oximeter placed on a gastroschisis silo to monitor intestinal oxygen saturation.

The use of a silo for temporary coverage of exposed viscera for newborns with gastroschisis has allowed gradual reduction of the externalized intestine into the abdominal cavity. However, there has not been an easy way to monitor blood perfusion to the intestine within the silo other than with visual examination. In addition, visual examination of bowel through the silo is sometimes difficult for medical staff due to serositis and peel over the bowel. We have adopted an approach to monitor oxygen saturation of silo-contained intestine by placing a pulse oximeter sensor on the surface of the transparent silo to detect intestinal ischemia. Pulse oximeter sensors were applied on both a patient's distal extremity and the silo on five consecutive patients who were born with gastroschisis. The sensor was left on the silo during the entire period of gradual reduction. Perfusion index, pulse and oxygen saturation were observed and checked against the sensor placed on a peripheral extremity. The silo-placed pulse oximeter and peripheral pulse oximeter sensors showed a similar pulse and oxygen saturation throughout the reduction period in all five patients. In general, perfusion index was higher from the silo pulse oximeter compared to the peripheral pulse oximeter reading. A pulse oximeter can be used to monitor intestinal oxygen saturation contained within a silo and help modulate the rate of manual reduction of intestine.

Gastroschisis↗

Tissue ablation-rate measurements with a long-pulsed, fibre-deliverable 308 nm excimer laser.

This ablation rate study has been carried out with a fibre-deliverable, 308 nm, XeCl laser, producing long pulses of 200 ns as opposed to the usual 10-20 ns. This in-depth study aimed to evaluate the ablation rates for this longer pulse length. The effects on the ablation depth of dentine, enamel, soft tissue and bone were investigated ex vivo. Radiant exposure, number of pulses, pulse repetition rate and spot size were independently varied. For all tissues, ablation depth per pulse was found to increase, initially, linearly with radiant exposure. For both dentine and soft tissue a saturation radiant exposure was determined; thereafter the ablation rate decreased. The depth per pulse increased linearly with repetition rate but decreased logarithmically with both number of pulses and spot size. The ablation depth due to a 200 ns pulse is comparable to that caused by a 10-20 ns pulse but has the advantage of fibre delivery.

Animals↗

Comparison of ablation efficacy of excimer, pulsed-dye, and holmium-YAG lasers relevant to shock waves.

Ablation efficacy of pulsed lasers on human arterial tissue and associated shock waves have been investigated by means of excimer laser at 308 nm, pulsed-dye laser at 480 nm, and holmium-YAG laser at 2.1 microns. A multifiber catheter was used for lasing at 420 mjoules/pulse with holmium-YAG, 18.9 mjoules/pulse with excimer, and 100 mjoules/pulse with pulsed-dye laser. Ablation efficiency (ablated volume/energy) was greatest with pulsed-dye laser in blood and excimer laser in saline solution. There was selectivity for atheroma with pulsed-dye laser (ablation efficiency in atheroma versus normal tissue, 58 versus 27 x 10(-2) mm3/joule in blood; p less than 0.005) and holmium-YAG laser (12.6 versus 5.6 x 10(-2) mm3/joule in blood; p less than 0.001). Ablation efficiency of pulsed-dye laser was enhanced by blood (0.58 in blood versus 0.17 mm3/joules in saline for atheroma; p less than 0.005). Shock waves were correlated with ablation efficiency (r = 0.63 and 0.74 for pulsed-dye laser and holmium-YAG laser, respectively). There was neither selectivity for atheroma nor influence of blood medium with excimer laser. Only holmium-YAG laser could ablate tissue at a distance from the target in the blood medium. Histologic findings showed that all lasers could create smooth-edged craters with minimal coagulation necrosis. In conclusion, laser irradiation with holmium-YAG and pulsed-dye lasers could selectively ablate atheromatous tissue with minimal thermal injury, whereas excimer laser could not. Ablation efficiency was correlated with shock waves. Efficiency of pulsed-dye laser was enhanced by blood.

Angioplasty, Laser↗

Improved internal defibrillation with twin pulse sequential energy delivery to different lead orientations in pigs.

Internal cardiac defibrillation with an intravascular catheter was compared with a new method for internal cardiac defibrillation using 2 pulses delivered in sequence directly to the myocardium. For the sequential pulses, the first pulse was passed through an intravascular catheter (Medtronic 6880), between the anode in the superior vena cava-atrial junction region and the cathode in the apex of the right ventricle. The second pulse was delivered between the catheter tip in the right ventricular apex as cathode and an oval plaque electrode (Medtronic TX-7) secured on the epicardium of the left ventricular free wall as anode. Defibrillation pulses were of truncated, trapezoidal waveform (65% tilt), separated by 1, 10 and 100 ms. Using the catheter alone, 36 normal pig hearts could be defibrillated by 44 J. However, 22 pig hearts (60%) could not be defibrillated with energies below 35 J. Defibrillation threshold was improved with sequential twin pulses, the improvement being dependent on pulse separation (42, 34 and 19 J, at 100-, 10- and 1-ms separation, respectively; F = 14.6, df = 2.29, p less than 0.01). In conclusion, sequential twin pulse defibrillation provides a considerable reduction in energy necessary for defibrillation in comparison to single pulses using the catheter alone. In this study, the optimal separation was 1 ms.

Animals↗

Time to first pulse after automatic implantable cardioverter defibrillator implantation.

Should automatic implantable cardioverter defibrillator (AICD) power sources be explanted and discontinued if they have not pulsed during the first generator life? We have followed 59 patients an average of 23 months (range, 3 days to 8.4 years) after AICD implantation. The indication for AICD implantation was based on clinical dysrhythmia, history of sudden death, and findings at electrophysiologic study. Thirty-eight of 59 patients (64%) had experienced sudden death and 52/58 (90%) were inducible at electrophysiologic study. Excluding 5 inappropriate pulsing episodes, 31 of 59 patients (53%) had 235 pulses (range, 1 to 36; median, 2 pulses). The time to first pulse after implantation ranged from 1 day to 3.5 years with a median time of 2 months. In 6 patients, the first pulsing occurred later than 1 year after AICD implantation. Fifteen generators demonstrating impending power source failure have been replaced in 11 patients. Power source depletion occurred at an average of 24.1 months (range, 8 to 40 months). In 3 patients, the first pulsing occurred after generator depletion and replacement. By univariate analysis, none of 13 variables (sex, age, cardiac disease process, functional class, previous myocardial infarction, sudden death history, ejection fraction, type of dysrhythmia, inducibility with electrophysiologic testing, number of extra stimuli required for induction, left ventricular aneurysm resection, endocardial resection, or concomitant operation) was found to be a predictor of pulsing (p greater than 0.05). We conclude that the majority of patients with pulses after AICD implantation will have them during the first 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of blockade of alpha 1- and alpha 2-adrenoceptors on vasoconstrictor responses to single and twin pulse stimulation in rat tail artery.

Perfused/superfused proximal segments of Sprague-Dawley rat tail artery were stimulated at supramaximal voltage with two 1 ms square wave pulses. The pulse interval was either 10 or 20 s. With either interval the response to each pulse was similar, amounting to about 20 mm Hg increase in perfusion pressure. Prazosin (0.1 nM) approximately halved the response to both pulses whereas idazoxan (30 nM) was without effect. With an interval of 10 s, cocaine (4 microM) greatly increased the response to the first but not to the second pulse; in the presence of cocaine, prazosin (1 nM) again reduced both responses whereas idazoxan (30 nM) reduced the response to the first pulse but increased the response to the second. With an interval of 20 s, cocaine increased the responses to both pulses to a similar degree; in the presence of cocaine, idazoxan reduced the responses to both pulses. The results suggest that in rat tail artery, inhibition of the neuronal uptake process is required if noradrenaline released after stimulation with a single pulse is to reach smooth muscle alpha 2-adrenoceptors, and if feedback inhibition is to persist for more than 10 s.

Adrenergic alpha-Antagonists↗

Islet hormone pulse intervals are dependent upon sampling frequency.

Pulsatile insulin secretion has been reported from a variety of in vivo and in vitro systems. While it is agreed that insulin pulses exist, there is little agreement concerning the basal frequency or interpulse interval either within the same species in vivo, as both long and short term pulses have been reported, or between in vivo and in vitro preparations. We propose that the frequency of sampling may have profound effects upon the calculated pulse interval. Three systems were used to test this hypothesis: 1) artificial test data were designed to produce regular pulses with an exact 11 min period, 2) perfusate insulin concentration from isolated canine pancreata sampled at 1 min intervals and 3) peripheral blood insulin concentrations from human volunteers sampled every 2 and 5 min. Pulse parameters were determined at 1, 2, 5, 20, 15, 30 and 60 min sampling intervals for each data set by the use of the computer algorithms Pulsar and Cycle Detector. The results indicate that for insulin secretory pulses, sampling frequencies longer than 2 min may result in the production of spurious pulse trains with multiple longer term pulse periods. It is concluded that islet hormone secretory pulse period calculations are dependent upon the sampling frequency.

Analysis of Variance↗

Pulse modulation detection in human motion vision.

We present data on the human sensitivity to temporal pulse modulations of target velocity. We measured threshold detection modulation amplitudes for pulse-shaped speed modulations, as a function of pulse duration and temporal frequency. At short pulse durations (up to 50 msec) and low modulation frequency (1 Hz), detection amplitudes are ruled by Bloch's law: the product of pulse duration and threshold modulation amplitude is a constant. This constant corresponds to a position modulation with an amplitude of 3 arc min in a coordinate frame that moves at the average speed (3 deg/sec) of the target. At longer pulse durations we find deviations from Bloch's law. Speed modulation thresholds are not critically dependent on target luminance contrast. These results are modeled by a modulation detection process in two stages. A functional description of the first stage is filtering of the true speed modulation signal by a second order low-pass filter with a characteristic time constant of 20-25 msec. The second (decision) stage is variance detection: modulations are detected when the variance of the filtered modulation function exceeds a certain threshold variance. The square-root threshold variance is estimated 8-10%. This two-parameter model accurately predicts the measured dependence of pulse modulation detection thresholds on pulse duration and pulse density.

Filtration↗

Effects of pulsed electric fields on mouse spleen lymphocytes in vitro.

The effects of pulsed electric fields on cell membranes were investigated. In vitro exposure of mouse splenocytes to a single high-voltage pulse resulted in an increase in membrane permeability that was dependent on both the electric field strength and the pulse duration. Exposure to a 2 microseconds, 3.0 kV/cm pulse resulted in the induction of a 1.26 V transmembrane potential, and elicited a 50% loss of intracellular K+. These results are in agreement with previous studies of the effects of pulsed electric fields on erythrocytes and microorganisms. The effect of pulsed electric fields on the functional integrity of lymphocytes was investigated by measuring [3H]thymidine incorporation by cells cultured in the presence and absence of various mitogens following exposure to an electrical pulse. No statistically significant effects on the response of mouse spleen lymphocytes to concanavalin A, phytohemagglutinin or lipopolysaccharide were observed following exposure to 2 microseconds electric pulses at amplitudes of up to 3.5 kV/cm. Exposure to a single 10 microseconds pulse of 2.4-3.5 kV/cm produced a statistically significant reduction in the response of lymphocytes to lipopolysaccharide stimulation that was attributed to cell death.

Animals↗

Interaction between paired-pulse facilitation and long-term potentiation in area CA1 of guinea-pig hippocampal slices: application of quantal analysis.

The aim of the study was to further specify mechanisms of maintenance of hippocampal long-term potentiation. Previous analysis of excitatory postsynaptic potentials showed increases in quantal content (mean number of neurotransmitter quanta released by every testing pulse) with smaller increases in quantal size (effect of one transmitter quantum) following long-term potentiation induction. Here we recorded intracellularly excitatory postsynaptic potentials from CA1 pyramidal neurons of guinea-pig hippocampal slices after minimal paired-pulse stimulation of monosynaptic inputs. Statistical parameters underlying excitatory postsynaptic potential fluctuations were estimated by a deconvolution procedure using a quantal model. The parameters of excitatory postsynaptic potentials following paired-pulse stimulation were studied before and after induction of long-term potentiation. Under both conditions, paired-pulse facilitation was found to be accompanied by increases in quantal content and quantal size. During long-term potentiation, paired-pulse facilitation of amplitude and quantal content was lower. The respective changes in the paired-pulse facilitation ratios correlated with long-term potentiation magnitude. In contrast, the paired-pulse facilitation of quantal size did not change significantly following long-term potentiation induction. The results are compatible with the existence of two separate mechanisms of long-term potentiation maintenance. They support the suggestion that changes in quantal content are mainly due to presynaptic mechanisms which are shared by long-term potentiation and paired-pulse facilitation. The mechanisms underlying changes in quantal size are of a different nature for long-term potentiation and paired-pulse facilitation. For long-term potentiation they might be located postsynaptically.

Animals↗

Why shorter half-times of repair lead to greater damage in pulsed brachytherapy.

PURPOSE: Pulsed Brachytherapy consists of replacing continuous irradiation at low dose-rate with a series of medium dose-rate fractions in the same overall time and to the same total dose. For example, pulses of 1 Gy given every 2 hr or 2 Gy given every 4 hr would deliver the same 70 Gy in 140 hr as continuous irradiation at 0.5 Gy/hr. If higher dose-rates are used, even with gaps between the pulses, the biological effects are always greater. Provided that dose rates in the pulse do not exceed 3 Gy/hr, and provided that pulses are given as often as every 2 hr, the inevitable increases of biological effect are no larger than a few percent (of biologically effective dose or extrapolated response dose). However, these increases are more likely to exceed 10% (and thus become clinically significant) if the half-time of repair of sublethal damage is short (less than 1 hr) rather than long. This somewhat unexpected finding is explained in detail here. METHODS AND MATERIALS: The rise and fall of Biologically Effective Dose (and hence of Relative Effectiveness, for a constant dose in each pulse) is calculated during and after single pulses, assuming a range of values of T1/2, the half-time of sublethal damage repair. The area under each curve is proportional to Biologically Effective Dose and therefore to log cell kill. RESULTS: Pulses at 3 Gy/hr do yield greater biological effect (dose x integrated Relative Effectiveness) than lower dose-rate pulses or continuous irradiation at 0.5 Gy/hr. The contrast is greater for the short T1/2 of 0.5 hr than for the longer T1/2 of 1.5 hr. CONCLUSION: More biological damage will be done (compared with traditional low dose rate brachytherapy) in tissues with short T1/2 (0.1-1 hr) than in tissues with longer T1/2 values.

Brachytherapy↗

Quantitative comparisons of continuous and pulsed low dose rate regimens in a model late-effect system.

PURPOSE: There is increasing interest and usage of pulsed low dose rate (PDR) brachytherapy, in which a single source is shuttled through the catheters of an implant, typically for about 10 min each hour. This study was designed to compare the late effects produced in various PDR regimens with those from the corresponding continuous low dose rate (CLDR) regimens. METHODS AND MATERIALS: A model late-responding system was used, namely, cataract induction in the rat lens. This system has the advantage of being highly quantifiable. The rats eyes were exposed to a total dose of 15 Gy either continuously over 24 h, or with three different PDR regimens, all with the same total dose and overall time. We addressed three questions: (a) are late effects increased when a CLDR regimen is replaced with 10-min pulses repeated every hour? (b) Are late effects increased if hourly 10-min pulses are replaced with 10-min pulses repeated every 4 h? (c) Are late effects increased if 10-min pulses are replaced with 100-s pulses? RESULTS: We found that the four regimens under test, continuous, 10-min pulses each hour, 10-min pulses every 4 h, and 100-s pulses every hour, showed no significant differences in cataractogenic potential, as estimated with the Wilcoxon-Gehan test. Power tests indicated that the experimental design was adequate to detect relatively small differences in cataractogenicity between regimens. CONCLUSIONS: The equality of late effects from CLDR and PDR in these experiments must imply that sublethal damage repair is quite slow in this model late-responding system, in agreement with trends observed in the clinic for sublethal damage repair of late sequelae. Such trends would suggest that PDR is unlikely to produce significantly worse late effects than the corresponding CLDR regimen, which is in agreement with early clinical data using PDR. Caution, however, is strongly recommended.

Animals↗

Pulse pressure is more susceptible to the white coat effect than is systolic blood pressure: observations from real-life ambulatory blood pressure monitoring.

BACKGROUND: Pulse pressure is a derivative of arterial stiffness. We have previously demonstrated ambulatory pulse pressure to be relatively independent from the blood pressure (BP) lowering during sleep, and thus of a neurogenic effect. On the other hand, white coat BP effects are thought to involve neurogenic activation. The aim of this work was to analyze white coat induced variability in pulse pressure. METHODS: Percent clinic-awake differences in systolic BP (SBP) and pulse pressure (white coat effects) were calculated for 688 consecutive subjects (mean age 60 +/- 16 years, 58% female). Of the subjects, 23% had controlled hypertension, 45% uncontrolled hypertension, 8% normotension, and 4% isolated office hypertension; all were referred to our unit for 24 h ambulatory BP monitoring. RESULTS: Pulse pressure highly correlated with SBP (r = 0.82, P <.00001). We found a larger white coat effect on pulse pressure than on SBP (8.3% and 5.2%, respectively, P < or =.0001). This was true in all subgroups except in normotensive subjects. Specifically, the magnitude of the white coat effect on pulse pressure was greater than on SBP in subjects with treated hypertension, untreated hypertension, and isolated office hypertension, and in young hypertensive subjects, older subjects, and those with diabetes. CONCLUSIONS: Although pulse pressure is related to the mechanical properties of large arteries, it is also influenced by the white coat effect, a neurogenic process. Furthermore, in hypertensive but not in normotensive subjects, the white coat effect on pulse pressure is significantly more pronounced than on SBP.

Adult↗

Composite model of time-varying appearance and disappearance of neurohormone pulse signals in blood.

Blood-borne neurohormonal signals reflect the intermittent burst-like release of peptides and steroids from neurons, glands and target tissues. Hormones control basic physiological processes, such as growth, metabolism, reproduction and stress-related adaptations. Secreted molecules undergo combined diffusion, advection and irreversible elimination from the circulation. Quantification of these interdependent processes by a structurally relevant model embodying discrete event times, continuous rates of secretion and elimination, and stochastic variations poses a formidable challenge. In an experimental setting, one observes only the hormone concentrations, which comprise a time-varying composite of secretion and elimination. The number, shape and location of underlying bursts (pulses) and attendant secretion and kinetic parameters are unobserved. The ability to estimate the properties of these processes from the observed data is fundamental to an understanding of regulated hormonal dynamics. The present formulation allows objective simultaneous appraisal of discrete (pulse times) and continuous (secretion/elimination) properties of neuroglandular activity in the presence of random variability. A probability distribution is constructed for the structural parameters (secretion/elimination, pulsing), and an algorithm is developed by which one can, based upon observed hormone concentration data, make probabilistic statements about the underlying structure: pulse frequency per day, total basal (constitutive) and pulsatile secretion per day, and half-lives of elimination. The algorithm consists of the following steps: first, explicit construction of a family of sequentially decreasing putative pulse-time sets for a given neurohormone concentration time series; and then, recursive iteration between the following two: (a) for a given pulse-time set, generate a sample from the probability distribution of unknown underlying hormone secretion and elimination rates; and (b) determine whether or not a probability-based transition from one pulse-time set to another is merited (i.e., add/remove a pulse-time or stay the same). We apply this procedure illustratively to joint estimation of pulse times, secretion rates and elimination kinetics of selected pituitary hormones (ACTH, LH and GH).

Activity Cycles↗

High-efficiency gene electrotransfer into skeletal muscle: description and physiological applicability of a new pulse generator.

Efficiency and reproducibility of gene electrotransfer depend on the electrical specifications provided by the pulse generator, such as pulse duration, pulse number, pulse frequency, pulse combination, and current intensity. Here, we describe the performances of GET42, a pulse generator specifically designed for gene electrotransfer into skeletal muscle. Expression of beta-galactosidase in the Tibialis anterior muscle of Sprague-Dawley male rats was increased 250-fold by GET42 compared to DNA injection alone. Combination of high and low current intensity pulses further increased transfection efficiency (400-fold compared to DNA injection without electrotransfer). Varying degrees of muscle necrosis were observed after gene electrotransfer. Nevertheless, muscle necrosis was dramatically reduced after optimization of cumulated pulse duration without significant reduction in transfection efficiency. Physiological applicability was illustrated by the analysis of cytochrome c promoter transactivation. In conclusion, GET42 has proven to be a reliable and efficient pulse generator for gene electrotransfer experiments, and provides a powerful mean to study in vivo the regulation of gene expression.

Animals↗

Measurement of calcium channel inactivation is dependent upon the test pulse potential.

We have developed two methods to measure Ca2+ channel inactivation in Lymnaea neurons-one method, based upon the conventional double-pulse protocol, uses currents during a moderately large depolarizing pulse, and the other uses tail currents after a very strong activating pulse. Both methods avoid contamination by proton currents and are unaffected by rundown of Ca2+ current. The magnitude of inactivation measured differs for the two methods; this difference arises because the measurement of inactivation is inherently dependent upon the test pulse voltage used to monitor the Ca2+ channel conductance. We discuss two models that can generate such test pulse dependence of inactivation measurements-a two-channel model and a two-open-state model. The first model accounts for this by assuming the existence of two types of Ca2+ channels, different proportions of which are activated by the different test pulses. The second model assumes only one Ca2+ channel type, with two closed and open states; in this model, the test pulse dependence is due to the differential activation of channels in the two closed states by the test pulses. Test pulse dependence of inactivation measurements of Ca2+ channels may be a general phenomenon that has been overlooked in previous studies.

Animals↗