Effects of some different pulse parameters on bladder inhibition and urethral closure during intravaginal electrical stimulation: an experimental study in the cat

Intravaginal electrical stimulation (IVS) was used in the cat to induce bladder inhibition and urethral closure. The purpose of the study was to compare the efficacy of alternating constant-voltage pulses of different durations (0·1, 0·2, 0·5 and 5 ms) with that of chopped alternating pulses, each consisting of a train of five 0·5 ms pulses with 0·5 ms pauses between. The voltage requirement for an equal biological effect was lowest for the 5 ms alternating pulse, whereas the pulse power dissipation was lowest for the 0·1 ms pulse, about 10 per cent of that for the 5 ms pulse. If both voltage requirement and power dissipation are taken into account, the 0·5 ms pulse was considered the most appropriate compromise. The chopped pulse was the least efficient stimulus, since the threshold voltage was comparable to that of the 0·5 ms duration alternating pulse, implying a five times higher power dissipation. For bladder inhibition, the optimal stimulation frequency for alternating pulses was 10 Hz, both in terms of threshold voltage and power consumption. For urethral closure the voltage requirement was lowest at 50 Hz but 20 Hz was preferable in terms of power dissipation for an equal, although submaximal, effect.     

Efficacy and safety of the reciprocal pulse defibrillator current waveform

The efficacy and safety of a new defibrillating current waveform, consisting of a low-tilt 5 ms trapezoidal pulse followed closely by a second identical pulse of opposite polarity, was tested in seven isolated, perfused, working canine hearts suspended in an isoresistive, isotonic shock bath at 37°C. The efficacy and safety of the reciprocal pulse was compared with a single 5 ms pulse, a single 10 ms pulse, and a dual (unidirectional) 5ms pulse waveform. The mean threshold average current densities for the 5 ms single pulse, 10 ms single pulse, dual 5 ms pulse, and reciprocal pulse (absolute values) were 40, 38, 36 and 37 mA cm⁻², respectively. The corresponding mean threshold energy densities in the shock bath were 2·8, 2·9 and 3·1 mJ cm⁻³. Despite the differences in threshold current density among the waveforms, no differences in safety factor (shock strength for 50 per cent postshock depression divided by threshold shock strength) were found among the waveforms. The current safety factors were 5·4, 5·4, 5·6 and 5·5 for the 5 ms single pulse, 10ms single pulse, dual unidirectional pulse and reciprocal pulse, respectively. The corresponding energy density safety factors were 25, 27, 29 and 27. Thus the use of this reciprocal pulse waveform provides no advantage in efficacy or safety over waveforms of the same total duration.     

A programmable stimulator for physiological applications

The design of a computer controllable stimulator for use in the field of electrophysiology and neurophysiology is described. However, the unit is a self-supporting special timing device. Some preprogrammed types of stimulation available are: a double pulse, a train of N pulses and a stepwise variation of time interval. The unit is triggerable on physiological signals. Triggering is also possible for each interval timing. The pulses are available on three different isolated transformer-coupled current sources, supplied by a r.f. carrier. The delivered pulses are current stabilised and adjustable between 0·1 and 99 mA. The interval timing is adjustable between 0·1 ms and 9999 ms. The pulse duration may be varied between 0·1 ms and 99·9 ms. All parameters are set by means of thumb-wheel switches.     

Effects of some different pulse parameters on the perception of intravaginal and intra-anal electrical stimulation

Electrical stimulation was performed in male and female subjects by means of intra-anal and intravaginal electrode carriers. Rectangular constant voltage pulses of alternating polarity, pulse repetition rate 10 Hz, and pulse durations between 0·1 and 5 ms were tested. The perception of stimulation was used as a measure of stimulation efficiency and the voltage amplitudes at detection threshold and at maximum tolerance were recorded. The aim of the study was to determine the voltage requirements of a new, totally integrated stimulation device for intravaginal application. The voltage requirement of the 0·1 ms pulse was more than twice that of the 5·0 ms pulse for an equal effect, its power dissipation was considerably lower. The detection threshold was significantly higher with intravaginal than with intra-anal stimulation. There was also a larger variation in voltage amplitudes between female subjects, whereas the ratio between maximum tolerance and detection threshold amplitudes was quite small. In intra-anal stimulation the scatter in threshold voltage between male subjects was smaller, but an almost twofold increase of the threshold voltage amplitude was required to reach the maximum tolerance level. The study points to the necessity of having adjustable stimulation parameters in intravaginal stimulation devices. Stimulation efficacy may be changed equally well by varying pulse duration as pulse amplitude.     

Effects of defibrillation shock energy and timing on 3-D computer model of heart

We present computer simulations of electrical defibrillation in a three-dimensional model of the ventricles of the heart. In this model, calledHeartSim, the ventricles are represented by 1473 cubic elements with 3 mm sides. The action potential is described by five discrete states; absolutely refractory, three relatively refractory, and repolarized. Activation is propagated to an element's six orthogonal neighbors with the conduction velocity dependent on the refractory state of the neighbor. Delivery of several extra-stimuli with decrementing coupling intervals results in ventricular fibrillation. Following the onset of ventricular fibrillation, we simulate defibrillation using various electrode configurations, shock energies, and timings. The current density distributions in the heart model resulting from the defibrillation shocks are determined from finite element analysis of the electric fields produced by the delivery of high energy shocks. The simulations suggest that successful defibrillation shocks produce a short period of low activation followed by a complete cessation of activation for a duration of 387±162 ms. In contrast, unsuccessful shocks produce a significantly shorter period of low activation (70±12 ms) after which ventricular fibrillation resumes.HeartSim mimics the experimentally reported, highly variable response to near-threshold shocks — the energy for successful defibrillation varies widely (20.8±20.7 J). In addition, the success rate vs. energy curve has a sigmoidal shape that is consistent with experiments. We demonstrate that this variability in the energy requirement results from dynamic variability in the number of elements made refractory by the shock and the relative distribution of the activation pattern at the time of the shock. Further, we show that it may be possible to lower the defibrillation energy requirements by delivery of two successive low energy pulses. The most efficient timing for the second pulse corresponds to the repolarization of the elements that were excited by the first pulse. Thus, when the interval between the two pulses was 85±18 ms, the defibrillation threshold energy (DFE) is reduced by 30.7±10% with pulses of 10 ms duration, and 62.6±7.9% with pulses of 5 ms duration. Our simulations also show that there is a delicate balance of energy between the two pulses that must be reached in order to achieve energy reduction with double pulse defibrillation. In conclusion,HeartSim serves as a tool for studying the underlying mechanisms of the effects of DF shocks on ventricular arrhythmias, and assists in evaluation of improved strategies for shock delivery.     

Fundamental criteria underlying the efficacy and safety of defibrillating current waveforms

The efficacy (threshold average current density) and safety factor (overdose current density for a 50 per cent decrease in myocardial contractility) were determined for the rectangular, trapezoidal and damped sine wave defibrillating current waveforms using a new blood-perfused, isolated, working canine heart in an isoresistive and isotonic volume conductor. This preparation permits the achievement of defibrillation with the heart in as uniform a current density field as possible and eliminates myocardial deterioration due to the traditional loss of coronary perfusion during ventricular fibrillation. Since the heart is isolated, it is not subject to any neural influences. It was found that, for a given pulse duration, the threshold average current density (efficacy) values were very similar among the three current waveforms. It was also found that the safety factors for the three current waveforms ranged from 3·2 to 5·3, the conventional 4–6 ms damped sine wave having a safety factor of 5·0±0·9 (1SD).     

A pulse-train generator for biological stimulation

A circuit to generate periodically a series of rectangular pulses, or ‘train’, for biological stimulation is described. Analogue integrators are used to determine pulse duration, spacing, and train length from 0·05 to 5000 ms. The 0·10 V output may be used directly or to adapt conventional stimulators for train production. General-purpose integrated-circuit amplifiers, gates, and bistables are used to facilitate circuit construction and duplication.     

Thresholds of intradental A- and C-nerve fibres in the cat to electrical current pulses of different duration

Electrical current pulses of quite variable duration have been used in activation of intradental nerves both in human subjects and experimental animals. It seems, however, that little information is available about the effect of pulse duration on the responses of single pulp nerve units. The aim of the present study was to investigate the effect of pulse duration on excitation thresholds of intradental A- and C-fibres in the cat. In 12 anesthetized cats 61 C- and 53 A-nerve units were identified and recorded. Electrical thresholds were determined with current pulses of different duration from 0.2 to 50.0 ms. The maximal stimulus intensity was 200 microA. Conduction velocities of all recorded units and absolute refractory periods of 20 A- and 20 C-units were determined. Intradental A- and C-fibres had different strength-duration properties. with all pulse durations A-fibres had the lowest thresholds. Part of the C-fibres did not respond to the shortest current pulses even with the maximum stimulus intensity (200 microA). with 0.2 ms pulses only 31.1% of the recorded C-fibres could be activated. In some A-fibres a single current pulse of long duration was capable of inducing several action potentials, when the stimulus intensity was increased suprathreshold. Refractory periods of A-units were less than 2.0 ms and those of C-units 5.0-9.0 ms. It is concluded that in electrical stimulation of teeth duration of current pulses strongly affects responses of single intradental fibre units.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thresholds of intradental A-and C-nerve fibres in the cat to electrical current pulses of different duration

Electrical current pulses of quite variable duration have been used in activation of intradental nerves both in human subjects and experimental animals. It seems, however, that little information is available about the effect of pulse duration on the responses of single pulp nerve units. The aim of the present study was to investigate the effect of pulse duration on excitation thresholds of intradental A-and C-fibres in the cat. In 12 anesthetized cats 61 C-and 53 A-nerve units were identified and recorded. Electrical thresholds were determined with current pulses of different duration from 0.2 to 50.0 ms. The maximal stimulus intensity was 200 μA.Conduction velocities of all recorded units and absolute refractory periods of 20 A-and 20 C-units were determined. Intradental A-and C-fibres had different strength-duration properties. With all pulse durations A-fibres had the lowest thresholds. Part of the C-fibres did not respond to the shortest current pulses even with the maximum stimulus intensity (200 μA).With 0.2 ms pulses only 31.1% of the recorded C-fibres could be activated. In some A-fibres a single current pulse of long duration was capable of inducing several action potentials, when the stimulus intensity was increased suprathreshold. Refractory periods of A-units were <2.0 ms and those of C-units 5.0–9.0 ms. It is concluded that in electrical stimulation of teeth duration of current pulses strongly affects responses of single intradental fibre units. With long pulses function of A-fibres is pronounced because of repetitive firing in some units. These properties of pulp nerves should also be considered, when electrical stimulation is applied to human teeth.     

Miniaturised device for long-term intravaginal electrical stimulation for the treatment of urinary incontinence

A miniaturised, totally integrated device intended for long-term treatment with electrical stimulation of female urinary incontinence has been designed. The device, which is moulded in epoxy resin, contains a hybrid circuit and a battery supply. The battery cells are recharged by constant current delivered to the stimulation electrodes by an external unit. The stimulation electrodes are band-shaped and made of stainless steel. The electric device has an oval cross-section to conform with the anatomy of the vagina, and is designed to be of minimum size while maintaining safe encapsulation of the electrical components. Electrical stimulation is applied as constant-voltage pulses of alternating polarity. The pulse repetition rates are selected to be 10, 50 or 20 Hz for the treatment of urge, stress or mixed urge-stress incontinence, respectively. The pulse duration is variable from 0·1 to 5ms, whereas the stimulation voltage amplitude is fixed. The stimulation is intermittent, lasting 10s and interrupted for 20s. The device should be recharged approximately once a week in normal use to maintain stimulation efficiency.     

Voltage-dependent effect of a scorpion toxin on sodium current inactivation

In voltage clamped nodes of Ranvier inactivation of the sodium permeability is slowed by toxin V from the scorpion Centruroides sculpturatus, by sea anemone toxin ATX II or by internally applied KIO3. The slow decay of the Na inward current is markedly accelerated if the test pulse is preceded by a depolarizing conditioning pulse followed by a 10-500 ms pause. This phenomenon was studied in detail, using conditioning pulses of varying amplitude and up to 15 s duration. In nodes treated with toxin V a 20 ms conditioning pulse to positive potentials was sufficient to produce a clear acceleration of the decay of the Na current and a reduction of the inward current remaining at the end of a 50 ms test pulse, i.e. a weakening of the toxin effect. In nodes treated with ATX II or internal KIO3 longer conditioning pulses were required. A similar effect of conditioning pulses on the decaying phase of the Na current was also observed in untreated fibres. To study the phenomenon quantitatively we fitted the decaying phase of the inward Na current with the equation INa = A exp(-t/tau 1) + B exp(-t/tau 2) + C. The effect of depolarizing conditioning pulses could be described as an increase of A, a decrease of B and C and a reduction of the time constants tau 1 and tau 2. I50/Ipeak, the normalised inward current remaining at the end of a 50 ms test pulse, decreased exponentially with increasing duration of the conditioning pulse to a steady-state value. The time constant tau and the steady-state value depended on the potential during the conditioning pulse. For nodes treated with toxin V, tau was 0.24 s at 0 mV and 12 degrees C and half inhibition occurred at -42 mV. The time constant tau was larger for nodes treated with ATX II or internal KIO3. At positive potentials, I50 was reduced to 20% of the control value in toxin V-treated nodes, but only to 70% in KIO3-treated nodes. Recovery from the effect of the conditioning pulse was studied by varying the pause between conditioning pulse and test pulse; recovery was 66-100% complete after 500 ms. The results are interpreted by assuming that a depolarizing conditioning pulse (a) accelerates inactivation of the sodium permeability and (b) causes dissociation of the toxin-receptor complex or transition into an inactive state. The latter effect occurs in toxin V-treated fibres but not in those treated with ATX II or KIO3.     

Startle response to short acoustic stimuli in rats

The acoustic startle (ASR) is a transient motor response to an unexpected, intensive stimulus. The response is determined by stimulus parameters such as its intensity, rise time and duration. The dependence of the ASR on the stimulus duration is more complex than could be assumed from physical properties of acoustic pulse. This effect attracted the attention of few researchers. Some authors reported noticeable changes in the ASR amplitude only for very short (less than 4-6 ms) acoustic pulses. The systematic studies on the effect, however, have not been performed so far. The purpose of this study was to determine to what extent the ASR parameters are affected by the durations of the short stimulus. The amplitude of the acoustic startle reflex was assessed for a fixed tonal frequency (6.9 kHz), and for a variety of stimulus durations ranging between 2 and 10 ms. ASRs were studied in 11 adult, hooded rats exposed to a sequence of tone pulses (110 dB SPL) of different durations, presented in random order, with or without 70 dB white noise as a background. Statistical analysis revealed significant differences between ASR amplitudes for different durations. The startle amplitude increased with acoustic pulse duration and distinguishable differences were seen for stimulus duration between 2 and 8 ms. Further increase of pulse duration had no effect on ASR amplitude. The same pattern of changes was observed when the acoustic stimulus was presented with the white noise. In the tested range of stimulus duration no significant differences in the ASR latency were found. The observed differences may be attributed to changes of stimulus acoustic energy and to physiological characteristic of auditory system in the rat.     

Transventricular defibrillation thresholds using quarter and half sinusoidal pulses

Transventricular peak current defibrillation thresholds using quarter (5 ms) and half (10 ms) sinusoidal pulses were determined in dogs under conditions of normothermia. For 5 ms, the overall average was 59·6 mAg⁻¹ of heart (s.d. 21·00) in a total of ten animals and 88 successful defibrillations. For 10 ms, the average over seven dogs and 51 determinations was 52·5 mAg⁻¹ of heart (s.d. 15·4). This difference was not statistically significant, whereas the energy delivered in the latter was about twice as much as in the former, suggesting the quarter sine wave pulse was better for defibrillation. A tighter definition of threshold is also introduced, i.e. the midrange between the maximum value which did not defibrillate and the minimum that did defibrillate. Such a definition is more realistic because it takes into account the successful and also the unsuccessfulvalues within a band of overlapping data points. The thresholds so obtained (52·3 mAg⁻¹, s.d. 15·7, nine dogs, 5 ms; 42·9 mAg⁻¹, s.d. 6·56, fourdogs, 10 ms) were, as expected, somewhat lower than the above mentioned ones showing, at the same time, lower coefficients of variation.     

Theory and design of capacitor electrodes for chronic stimulation

Conventional metal electrodes generate electrochemical byproducts during stimulation of nerve or muscle. These byproducts may cause tissue damage, especially with the long-term stimulation necessary with neural prosthetic devices. To prevent the possibility of such damage, completely insulated electrodes have been devised which deliver current pulses by capacitive charging of the electrode surface, not involving electrochemical reactions. Anodised discs of porous tantalum, 1·0 mm in diameter and 0·25 mm thick, can deliver 0·5 ms, 5 mA pulses. Such electrodes are available as components of commercial capacitors and are easily adapted for biological use. The design may be optimised by mathematical analysis of an equivalent electrical circuit.In vitro tests demonstrate a clear advantage of these electrodes over capacitively coupled platinum-iridium electrodes in preventing oxidation-reduction reactions. The electrodes are stable on chronic implantation and should provide a safer interface between neural prosthetic devices and human tissue.     

Intracellular [Ca2+] transients in voltage clamped cardiac Purkinje fibers

The Ca²⁺-activated bioluminescent protein aequorin was used to observe intracellular [Ca²⁺] transients in voltage clamped canine Purkinje fibers. The pattern of luminescence during a voltage clamp pulse was characterized by two components: L₁, which is a rapid initial increase in luminescence and L₂, which is a slower, secondary rise of variable configuration.

1. L₁, L₂, inward current, and contraction were abolished by D 600 (2 μM).
2. Paired clamp pulses. L₁ reprimes more rapidly than L₂; L₁ reprimes within 100 ms, L₂ does not.
3. Clamp pulse duration. Peak inward current was the same for 50 ms or 500 ms clamp pulses; L₁ was either the same or slightly reduced in 50 ms clamp pulses compared to 500 ms clamp pulses. L₂, however, was abolished in repetitively given 50 ms pulses compared to repetitively given 500 ms pulses. When 500 ms pulses were alternated with 50 ms pulses, L₂ was greater in the 50 ms pulse than in the 500 ms pulse.
4. Clamp pulse potential. In the range ?35 to 0 mV, peak L₁ and peak inward current occurred at nearly the same time, had the same threshold potential, and had a similar dependence on membrane potential.

In the presence of L₂, contractions develop severalfold greater peak tension, time to peak tension is longer, and relaxation is more rapid than in the absence of L₂. It is concluded that Ca²⁺ released from stores accounts for L₂ and most of the ‘activator calcium’. Ca²⁺ from another source accounts for L₁ and activates a small early component of the contraction. L₁ has some properties expected for a signal related to Ca²⁺ entering via slow inward current, but not via Na/Ca exchange.     

Asymmetrical displacement currents in the membrane of frog myelinated nerve: Early time course and effects of membrane potential

1. Asymmetrical displacement currents were studied in myelinated nerve fibres from Rana esculenta with a voltage clamp technique. 2. For brief pulses symmetrical with respect to a holding potential of--97mV, the asymmetry current flowing during pulses (on-response) exhibited a rising phase to a peak followed by an approximately exponential decline. After the pulses the rising phase in the off-response could not be resolved; the time constant varied about 2-fold with either size or duration of the pulse. 3. For longer pulses a second slower component could be detected both in on- and off-responses. 4. The rapidly declining on- and off-responses associated with brief pulses carried about the same charges Qon and Qoff. Increasing the duration of the pulse reduced Qoff. For all pulses tested Qoff approached about one fifth of Qmax. The reduction of Qoff was roughly characterised by time constants ranging between 1.5 and 0.5 ms for potentials between--25 and + 23 mV. Analysis of individual membrane currents confirmed that the capacity current after depolarizing pulses decreased with pulse length. 5. The effects of membrane potential on asymmetry current were studied by varying the level from which pulses were applied during 46.9ms prepulses in the range from--97 to--29mV. The fast and slow components of asymmetry current were affected differently. For potentials more positive than--90mV the fast on-response was reduced and reversed its sign at a potential 25mV more negative than the potential estimated from the steady-state charge distribution measured from--97mV.     

Intestinal-prostatic impedance measurements in bulls

The average intestinal-prostatic impedance in unanaesthetised bulls at ejaculation was experimentally evaluated by the application of known stimulating rectangular pulses (2 ms width, repetition rates between 25–35 pulses/s) and found, on average, to be of the order of 65·9Ω (s.d.=9) over a total of 14 ejaculations in eleven animals. The corresponding mean ejaculatory stimulating current dose was 0·507 mA/kg (s.d.=0·181). In all cases, the total current for full ejaculation was higher than 170 mA. An empirical relationship between biological impedance and applied current (124 data points) was also determined, showing, as expected, a decrease with increasing current and tending to a constant value in the order of 62Ω (s.e.e.=12) for la=288 mA. This impedance (which is faced by the stimulating electrodes inserted in the rectum) can be very easily estimated by means of the well known impedance technique at higher frequencies. In these experiments and at 12 kHz, the average over 44 measurements was 59·3 Ω (s.d.=10·7), a value very close to those given above and, therefore, useful in the design of adequate electroejaculators.     

Inactivation of the asymmetrical displacement current in giant axons of Loligo forbesi.

1. Asymmetrical displacement currents ('gating currents') have been recorded in intracellularly perfused squid giant axons by averaging the currents associated with depolarizing and hyperpolarizing pulses. The relation between 'gating current' and Na inactivation was studied by investigating the effect of pulse duration and conditioning pulses. 2. Increasing the pulse duration from 0-3-1 msec to 10-20 msec reduced the off-response of the 'gating current' to 50-70% of its normal size; the time constant was 5 msec at +20 mV and 8 degrees C. The decrease of the Na current during a 10-20 msec pulse was stronger and faster; it decayed to 10-26% with a time constant of 1-35 msec. 3. The effect of pulse duration could also be demonstrated by using only depolarizing pulses. The charge displacement at the end of single or averaged depolarizing pulses was smaller for long pulse durations than for short. A long depolarizing pulse was followed by a small long-lasting tail of inward current. 4. A conditioning depolarizing pulse of 10-20 msec duration to a potential of -30 or +10 mV, followed by a short recovery period at -70 mV, decreased the on-response of the 'gating current'. Its size was reduced to 46-71% and 61-94%, respectively, for a recovery interval of 1-75 and 5 msec at 2-3 degrees C. The reduction of the Na current, measured under similar conditions, was more pronounced; the Na current was decreased to less than 50% of its normal value. 5. The observations about the effect of pulse duration and conditioning pulses on the 'gating current' are qualitatively consistent with those of Bezanilla & Armstrong (1974, 1975) and support the view that part of the asymmetrical charge displacement is inactivated during a 10-20 msec depolarization.     

Amplitude-duration relation for direct ventricular defibrillation with rectangular current pulses

In this study it is demonstrated that, for defibrillation with a rectangular pulse, the relationship between threshold current strength and pulse width can be approximated by a hyperbola. Also the threshold charge and energy required for effective defibrillation are presented as functions of the pulse duration. From these three curves it can be seen that, for a rectangular pulse, the current strength is minimal for a duration between 20 and 40 ms, the charge, for a ‘zero’ duration and the energy for a duration of around 4 ms. Myocardial performance is generally assumed to be, minimally disturbed after a defibrillation shock if the applied current, charge and energy of one pulse are all minimal. Then it can be concluded that, for a rectangular pulse, no duration can be advised for defibrillation with the least myocardial disturbance after the shock, since current, charge, and energy have their minimums at different, pulse durations.     

The cathodal OFF response of electric taste in rats

Summary The cathodal OFF response in electric taste, the production of a taste sensation at the break of a microampere cathodal current passed through the tongue, was studied electrophysiologically in the rat chorda tympani nerve. Previous work in electric taste has centered on ON responses to both anodal and cathodal currents. The cathodal OFF response, like ON responses, increased with increasing current intensity until a saturated response level was achieved. Unlike previously reported ON responses, the OFF response did not show a sensitivity to the ionic composition of the fluid bathing the tongue making this the first electrophysiological report of ion insensitivity in electric taste. The cathodal OFF response was sensitive to the duration of the current pulse preceding it. Longer pulses produced larger OFF responses, until with very long pulses (seconds) a saturated response level was achieved. The half maximal response occurred at 12.5 ms. These results have been interpreted to mean that the cathodal OFF response has an origin other than the microvillus membrane, the site most often implied for ON responses, due largely to its ion insensitivity. A probable location may reside with ion channels transversing the basal membrane which are transiently excited at the break of the current resulting in excitation at the receptor-afferent synapse.