Constant Current Stimulation Research Articles

A New System and Paradigm for Chronic Stimulation of Denervated Rat Muscle.

Traditionally, animal studies employing electrical stimulation for conditioning denervated muscle rely on 24-hour-based stimulation paradigms, most employing implantable stimulators. While these stimulators provide the necessary current to cause muscular contraction, they have problems with battery life, programmability, and long-term robustness. Continuous 24-hour stimulation, while shown to be effective in animals, is not easily translatable to a clinical setting. It is also difficult to evaluate animal comfort and muscular contraction throughout a 24-hour period. We have developed a system and stimulation paradigm that can stimulate up to five animals at one time for one hour per day. The constant current stimulator is a USB-powered device that can, under computer control, output trains of pulses with selectable shapes, widths, durations and repetition rates. It is an external device with no implantable parts in the animal except for the stimulating electrodes. We tested the system on two groups of rats with denervated gastrocnemius muscles. One group was stimulated using a one-hour-per-day, 5-days-per-week stimulation paradigm for one month, while the other group had electrodes implanted but received no stimulation. Muscle weight and twitch force were significantly larger in the stimulated group than the non-stimulated group. Presently, we are using the stimulator to investigate electrical stimulation coupled with other therapeutic interventions that can minimize functional deficits after peripheral nerve injuries.

Rippling the cortex with high-frequency (>100 Hz) alternating current stimulation

A wide range of non-invasive brain stimulation techniques are currently available which can induce lasting changes in the excitability of the stimulated cortex (Ziemann et al. 2008). Regular repetitive transcranial magnetic stimulation (rTMS) and constant transcranial direct current stimulation (c-tDCS) are well-established stimulation modalities that have now been used for more than 10 years. Other stimulation techniques have only recently been introduced, such as continuous transcranial alternating current stimulation (c-tACS), oscillatory tDCS (o-tDCS) or patterned rTMS protocols. Currently, c-tDCS uses weak currents up to 2 mA which induce currents in the cortex that are far below the threshold for inducing action potentials. The tissue current is still strong enough to polarise the membrane potential of cortical neurons, resulting in lasting shifts in the resting membrane potential and associated changes in postsynaptic spiking activity. These effects are thought to mediate the after-effects of c-tDCS. A different mechanism is emphasized when c-tACS is used to manipulate cortical plasticity. Here the assumption is that the oscillatory current interacts with and shapes intrinsic neural oscillations in the stimulated cortex. Indeed recent studies support this notion showing that c-tACS can interact with brain function in a frequency specific manner (Kanai et al. 2008; Pogosyan et al. 2009). In an article in this issue of The Journal of Physiology, Moliadze et al. (2010) significantly add to this line of research. In healthy volunteers, 10 min of c-tACS of the human motor hand area (M1hand) at 140 Hz but not at 80 Hz enhanced regional corticospinal excitability during and for at least an hour after c-tACS. At 250 Hz, c-tACS also induced an increase in corticospinal excitability but to a lesser extent and with a delayed onset of facilitation. The increase in corticospinal excitability (measured by motor evoked potential amplitude in a hand muscle) was paralleled by a relative decrease in short latency intracortical inhibition (SICI), an electrophysiological marker of GABAA receptor mediated inhibition. Although Moliadze et al. (2010) are cautious to draw firm conclusions, they favour the hypothesis that tACS at 140 Hz targets cortical ripples and the resulting after-effects are due to an interaction between externally applied high frequency oscillation in the ripple range and intrinsic cortical ripple activity in M1hand. This is a possible scenario as ripple oscillations in the frequency range from 80 to 200 Hz have been demonstrated in the cat cortex, yet they are mainly expressed during non-REM sleep (Grenier et al. 2001). Furthermore, pulsed stimulation in the ripple range (130 Hz) of afferents to the subthalamic nucleus is therapeutically effective in Parkinsonian rodents (Gradinaru et al. 2009) and is being used for deep brain stimulation in human patients. The perspective that transcranial stimulation can be tuned to specifically target cortical oscillatory in specific frequency bands is intriguing. Oscillatory patterning of neuronal activity in different frequency bands supports temporal coding of different aspects of cortical processing (Singer, 2009). Therefore, transcranial stimulation protocols that can efficiently manipulate specific oscillatory activity might be more efficient and specific with respect to shaping specific brain functions than conventional regular rTMS or c-tDCS. At first glance, it seems straightforward to postulate that transcranial stimulation protocols should mimic as close as possible the temporal pattern of the intrinsic cortical oscillations that one wishes to modulate with transcranial stimulation. However, a number of general questions need to be clarified.

Electrical Stimulation and Electrode Properties. Part 2: Pure Metal Electrodes

ABSTRACT.Electrical stimulation can cause significant damage to clinical electrodes as well as patient injury. In this study, the effects of stimulation on pure metal electrodes were investigated without the complexities introduced by the multiple elements that make up the clinical electrode. As with the clinical electrodes, there was significant decomposition of pure stainless steel anodes with no associated significant changes in the cathodes when stimulation employed long pulse durations. Effects of stimulation were greater when the anode and cathode were closer under constant voltage stimulation but were distance independent under constant current stimulation. High ionic content of the solution also increased the degree of damage to the anode as did the presence of chloride in the solution. Electrode composition also influenced the amount damage to the anode. Platinum and platinum-iridium electrodes showed no damage with any stimulus while stainless steel showed the lowest resistance to corrosion for direct current (DC) stimulation. Tungsten electrodes behaved very differently than stainless steel, decomposing with pulse stimulation and resisting decomposition during DC stimulation because of the formation of surface protective layers.Because platinum was able to maintain high levels of current over time, prolonged stimulation produced dramatic increases in the temperature of the solution; however, even short periods of stimulation were sufficient to produce dramatic changes in pH in the neighborhood of the electrode.

Assessment of Patient Preference for Constant Voltage and Constant Current Spinal Cord Stimulation

Spinal cord stimulation devices control energy by generating either constant voltage (CV) pulses or constant current (CC) pulses. This study aimed to investigate: 1) whether patients feel differences between CV and CC stimulation; 2) if patients prefer CV or CC stimulation. Fourteen patients blinded to the type of pulse generation received 20 randomized pairs of 15-sec pulse trains (CC-CV, CV-CC, CV-CV, or CC-CC). Patients identified whether the pairs were the same or different, and if they preferred the first or second train. There was no difference in charge-per-pulse input between CV and CC modes. Patients performed at chance level in identifying identical pairs (55.7 ± 24.1% correct, 10 trials), and slightly better in identifying different pairs (67.1 ± 25.2% correct, 10 trials). No patients correctly identified all pairs. Patients were categorized based on their performance in this task. Only three patients fell into a category where preference could be established with some confidence with respect to the group averages. Two of these patients preferred CV, while one patient preferred CC. The lack of patient ability to discriminate in this preliminary investigation suggests that patient preference for a stimulation type should not be the key determining factor in choosing a spinal cord stimulation system.

Long-Term Measurement of Therapeutic Electrode Impedance in Deep Brain Stimulation

Deep brain stimulation technology now allows a choice between constant current and constant voltage stimulation, yet clinical trials comparing the two are lacking. Impedance instability would theoretically favor constant current stimulation; however, few publications address this with long-term follow-up. In this report, we review our series for impedance change and discuss our findings and their implications for future study design. A retrospective chart review was performed of all consecutive patients seen in the outpatient clinic for deep brain stimulation adjustments at the University of Wisconsin-Madison from February 2006 to May 2007. The following data were extracted: Quadrapolar contact selection, frequency, voltage, pulse width, and measured impedance at the therapeutic parameters. Patients were selected if consecutive measurements of therapeutic impedances for the same patient were performed with the same frequency, pulse width, voltage, and configuration of active contacts. A total of 63 patients with 110 electrodes had 301 documented programming visits. From these, 16 patients had 20 consecutive measurements with unchanged parameters in 19 electrodes at a median interval of 68 days and median follow-up of 549 days after implantation. No significant intra-patient intra-electrode therapeutic impedance variability was observed in this study (SD = 105.3 Ω, paired t-test, p= 0.312). In contrast, marked inter-patient variability in impedance was noted. This variability could not be explained by stimulation target, measurement interval, time since implantation, monopolar vs. bipolar stimulation, stimulation voltage, or stimulation frequency. No significant change in the same electrode therapeutic impedance was identified. Given the assumption that stimulation current is the critical parameter influencing clinical outcomes, these findings would not disadvantage constant voltage stimulation. However, inter-patient variability suggests a possible advantage for constant current stimulation when generalizing experience and comparisons over multiple patients. Further study of the relationship of stimulation efficacy to stimulation mode and impedance change is warranted.

Neuromuscular Block

Neuromuscular Block

Chronic vagus nerve stimulation decreased weight gain, food consumption and sweet craving in adult obese minipigs

Chronic vagus nerve stimulation (VNS) is known to influence food intake and body weight in animals and humans. The aim of our work was to evaluate the effects of long-term VNS in adult obese minipigs. Eight minipigs were fed ad libitum a Western diet to cause obesity, after which half of the animals were implanted with bilateral vagal electrodes connected to constant current stimulators (2mA, 30Hz, 500-μs pulse, ON 30s, OFF 5min). The other animals were implanted with sham devices. Animals were weighed weekly and their daily consumption was measured. Still 14 weeks after surgery, VNS animals (70.3±3.3kg, P>0.10) did not significantly gain weight compared to sham animals (80.6±8.0kg, P<0.05). Furthermore, food consumption decreased in VNS animals (−18%, P<0.02) compared to sham animals (+1%, P>0.10). When subjected to a three-choice meal test (high-fat vs. high-carbohydrates vs. balanced diet), VNS animals decreased their sweet-food consumption compared to sham animals (P<0.05), and increased their balanced diet consumption in comparison to pre-surgery levels. Our results showed that chronic VNS decreased weight gain, food consumption and sweet craving in adult obese minipigs, which indicates that this therapy might be used to decrease appetite in the context of morbid obesity.

Current Waveforms for Neural Stimulation-Charge Delivery With Reduced Maximum Electrode Voltage

This paper contains results on the design of electrical signals for delivering charge through electrodes to achieve neural stimulation while reducing the peak electrode voltage. A generalization of the usual constant current stimulation phase to a stepped current waveform is presented. Techniques based on optimization and linear dynamic system theory are then applied to design the magnitude of each current segment in such a way as to minimize the maximum electrode voltage, while transferring a designated quantity of charge in a specified time. Experimental results are provided which validate the approach in saline and in neural tissue.

Describing The Percent Inactivation Versus Force Relationships And Predicting True Force With Polynomial Regression

PURPOSE: The purpose of this study was to examine the percent voluntary inactivation versus submaximal force relationships with polynomial regression to predict each subjects' true maximal voluntary contraction (MVC) capabilities. METHODS: Nine participants (mean±SD age=21±3 yrs) completed nine randomly-ordered isometric plantar flexions from 10 to 90% of the MVC. Transcutaneous electrical stimuli were delivered to the tibial nerve using a high-voltage constant-current stimulator (Digitimer DS7AH, Herthfordshire, UK). Doublets were administered at a supramaximal stimulus intensity during the submaximal MVC plateau and then again 3-5 s after the submaximal MVC trial at rest. Percent inactivation was calculated for each submaximal MVC. The nine subjects selected for this study demonstrated < 5% voluntary inactivation at the 90% MVC, which suggested that these subjects were highly activated. Percent voluntary inactivation versus force relationships were analyzed on a subject-by-subject basis using polynomial regression (linear, quadratic, and cubic models). The predicted true MVC for each subject was extrapolated with their best fit polynomial model. A paired-samples t test was used to compare the actual MVC to the predicted true MVC. RESULTS: Polynomial regression indicated that 3 of 9 subjects (33%) were best fitted with a linear model, 2 of 9 subjects (22%) were best fitted with a quadratic model, and 4 of 9 subjects (44%) were best fitted with a cubic model. The t test indicated that the actual MVC (mean±SD 446±114 N) was greater than the predicted MVC (mean±SD 405±124 N) values (P = 0.003). Percent difference for each subject between actual MVC versus predicted MVC values ranged from 0.7% to 20.5%. CONCLUSIONS: Fitting the percent inactivation versus force relationships of highly activated subjects resulted in 33% linear and 66% nonlinear relationships. These results suggested that these patterns should be analyzed on a subject-by-subject basis. However, the predicted true MVC values from the best fit polynomial models were significantly less than the actual MVC values.

Relationship of Q‐sweat to quantitative sudomotor axon reflex test (QSART) volumes

Q-Sweat, a commercial quantitative sweat measurement system, is modeled on quantitative sudomotor axon reflex testing (QSART). This study investigated the sweat response using Q-Sweat and Mayo-QSART recordings under identical conditions in healthy normal controls. Ninety-four participants were recruited for this study. All participants underwent randomized bilateral QSART recordings over the four standard recording regions. For both men and women, Wilcoxon signed rank tests of paired differences showed significantly lower volumes at each of the four sites for Q-Sweat vs. Mayo-QSART. Linear regression analysis was used to estimate the relationship between Q-Sweat and Mayo-QSART volume measurements separately for men and women. Although there was variability about the regression lines, these fitted models can be used to estimate the expected Mayo-QSART volume given an observed Q-Sweat volume, although it is preferable to use the Q-Sweat normative database directly. We hypothesize that the constant-current generator used in conjunction with Q-Sweat provides a less efficient iontophoresis of acetylcholine than the Mayo-constructed constant-current stimulator and results in lower volumes.

Temporolimbic Activation by Intracranial Electrical Stimulation

To evaluate the results of intracranial electrical stimulation (ICES) as a pre-surgical tool in order to select the side of the operation in bitemporal lobe epilepsy (BTLE) patients who underwent depth electrode (DE) implantation. We reviewed the files of 77 medically intractable BTLE patients who underwent ICES with positive results through implanted DEs and then were under surgical treatment. One year or more after surgery, we evaluated the outcome. ICES was performed through: 1) Square-wave bipolar stimulation with symmetrical pulses of 60 Hz for 0.5 ms was delivered by a constant current Nuclear Chicago stimulator; 2) An initial intensity of 0.5 mA, and subsequently progressively stronger currents at 1-2 and occasionally 3 or 4 mA; 3) The duration of a single stimulation was usually 5 seconds; 4) The volume of tissue effectively stimulated did not exceed 5 mm. We obtained habitual auras or seizures (clinical responses, CRs) in 74 patients and after-discharges, ADs in 61 of them, according to Engel's classification for post surgery outcomes. If CRs or ADs were obtained by stimulation of only one temporal lobe the result of epilepsy surgery tended to be better (Engel classes I or II) when the operation was done on the same side of positive CRs (15 cases) or ADs (14 cases), and tended to be worse (Engel classes III or IV) when the ICES had provoked bilateral responses or when the side operated on was contra-lateral to positive CRs (33 cases) or ADs (28 cases). Statistical analyses were performed in order to test these results and we found better post-operative results when the resection took place in the same side of positive responses to ICES (CRs: chi2 4.74 and p=0.0295; ADs: chi2 7.57 and p=0.0059). In addition to other methods (PET, MRI and neuropsychology) presurgical ICES can provide useful data in the process of identifying the temporal lobe to be targeted for resection in BTLE patients.

Acute Changes in Motor Cortical Excitability During Slow Oscillatory and Constant Anodal Transcranial Direct Current Stimulation

Transcranial oscillatory current stimulation has recently emerged as a noninvasive technique that can interact with ongoing endogenous rhythms of the human brain. Yet, there is still little knowledge on how time-varied exogenous currents acutely modulate cortical excitability. In ten healthy individuals we used on-line single-pulse transcranial magnetic stimulation (TMS) to search for systematic shifts in corticospinal excitability during anodal sleeplike 0.8-Hz slow oscillatory transcranial direct current stimulation (so-tDCS). In separate sessions, we repeatedly applied 30-s trials (two blocks at 20 min) of either anodal so-tDCS or constant tDCS (c-tDCS) to the primary motor hand area during quiet wakefulness. Simultaneously and time-locked to different phase angles of the slow oscillation, motor-evoked potentials (MEPs) as an index of corticospinal excitability were obtained in the contralateral hand muscles 10, 20, and 30 s after the onset of tDCS. MEPs were also measured off-line before, between, and after both stimulation blocks to detect any lasting excitability shifts. Both tDCS modes increased MEP amplitudes during stimulation with an attenuation of the facilitatory effect toward the end of a 30-s tDCS trial. No phase-locking of corticospinal excitability to the exogenous oscillation was observed during so-tDCS. Off-line TMS revealed that both c-tDCS and so-tDCS resulted in a lasting excitability increase. The individual magnitude of MEP facilitation during the first tDCS trials predicted the lasting MEP facilitation found after tDCS. We conclude that sleep slow oscillation-like excitability changes cannot be actively imposed on the awake cortex with so-tDCS, but phase-independent on-line as well as off-line facilitation can reliably be induced.

ATP released from sympathetic nerve endings in skeletal muscle arterioles

The purpose of this study was to determine the feasibility of measuring ATP released from sympathetic nerve endings in arterioles. Using F344 rats (2‐3 months old), the gastrocnemius 1A arterioles from the red gastrocnemius muscle were dissected and cannulated with glass pipettes in a tissue bath. ATP probes were connected to a potentiometer, polarized, zeroed, and a normal ATP curve generated (6.25µM to 50 µM ATP). The ATP and null probes were then positioned in the tissue bath such that the tips of the probes were submerged in the physiological saline solution and the tips were touching the arteriole in similar anatomical locations. The arterioles were then field stimulated at 60Hz for 2000 impulses at 9mA using a constant current stimulator. The normal curve produced 7.19mA at 50 µM ATP, 6.09mV at 25 µM ATP, 3.83mA at 12.5 µM. Following linear curve fitting, the slope of the line was 7.15x10−2 mA/uM ATP and an intercept of 3.22mA. Field stimulation at 60Hz produced 3.44mA that corresponded to 3.01 µM of ATP released. These data suggest that it is possible to measure ATP released from the sympathetic nerve endings from arterioles using potentiometry.

Funktionelle Untersuchungen von Ionenkanälen in unmyelinisierten Axonen des Menschen

Clinical assessment of large fibre neuropathy is a routine neurological procedure. The clinical assessment of small fibre function however is far less well established and as a consequence pharmaceutical therapies for small fibre neuropathies often comprise sequential trials with different medications until one works. To refine the diagnosis and treatment of small fibre neuropathies a fuller understanding of the physiological and pharmacological profile of human unmyelinated axons is required. To this end we have adopted the in vitro preparation of human sural nerve segments first described by Lambert and Dyck (1) and developed techniques to examine the excitability and chemosensitivity of human unmyelinated axons. Individual nerve fascicles were extracted from sural nerve segments taken at biopsy or after amputation and mounted between stimulating and recording suction electrodes in a small organ bath. The excitability of all unmyelinated axons within an individual fascicle was determined by monitoring the amplitude and latency of the compound C fibre action potential response to constant current electrical stimulation. Using threshold tracking techniques it is possible to monitor multiple excitability parameters (2) of human C-fibres during the application of pharmacological agents to the bathing solution. We have used this in vitro preparation to examine the effect of specific inflammatory mediators on the excitability of human C fibres as well as the ability of several compounds used in the clinical treatment of neuropathic pain to influence the effects of such mediators.

Determination of the minimum alveolar concentration of isoflurane in Shetland ponies using constant current or constant voltage electrical stimulation

ObjectiveTo determine the minimum alveolar concentration (MAC) of isoflurane in Shetland ponies using a sequence of three different supramaximal noxious stimulations at each tested concentration of isoflurane rather than a single stimulation. Study designProspective, experimental trial. AnimalsSeven 4-year-old, gelding Shetland ponies. MethodsThe MAC of isoflurane was determined for each pony. Three different modes of electrical stimulation were applied consecutively (2 minute intervals): two using constant voltage (90 V) on the gingiva via needle- (CVneedle) or surface-electrodes (CVsurface) and one using constant current (CC; 40 mA) via surface electrodes applied to the skin over the digital nerve. The ability to clearly interpret the responses as positive, the latency of the evoked responses and the inter-electrode resistance were recorded for each stimulus. ResultsIndividual isoflurane MAC (%) values ranged from 0.60 to 1.17 with a mean (±SD) of 0.97 (±0.17). The responses were more clearly interpreted with CC, but did not reach statistical significance. The CVsurface mode produced responses with a longer delay. The CVneedle mode was accompanied by variable inter-electrode resistances resulting in uncontrolled stimulus intensity. At 0.9 MAC, the third stimulation induced more positive responses than the first stimulation, independent of the mode of stimulation used. ConclusionsThe MAC of isoflurane in the Shetland ponies was lower than expected with considerable variability among individuals. Constant current surface electrode stimulations were the most repeatable. A summation over the sequence of three supramaximal stimulations was observed around 0.9 MAC. Clinical relevanceThe possibility that Shetland ponies require less isoflurane than horses needs further investigation. Constant current surface-electrode stimulations were the most repeatable. Repetitive supramaximal stimuli may have evoked movements at isoflurane concentrations that provide immobility when single supramaximal stimulation was applied.

A new integrated system for neural stimulation and bipolar coagulation: preliminary study

Conclusion. Tthe proposed device can be useful for promoting safety during bipolar coagulation in many surgical procedures and/or regions. Objective. A new system that integrates a neural stimulator and a bipolar coagulator is proposed, to improve neural (facial nerve) safety during ENT surgical procedures. This study aimed to evuate the system. Materials and methods. A home-made constant current neural stimulator (0.1–2 mA, pulsed, duration 200 µs), was connected via an automatic switch to a commercial bipolar microcoagulator (Medicon Instrumente mod. 101, Germany). Under general anesthesia, the extra-petrous portion of the facial nerve was identified in three rabbits. The adequate functioning of the device was tested via: 1) neural stimulation and EMG monitoring in basal conditions; 2) bipolar coagulation of connective tissue surrounding the facial nerve; 3) final assessment of the functional integrity of the nerve, via an intraoperative EMG and a postoperative evaluation. Results. Data obtained from all three rabbits provided adequate results in terms of neural stimulation, correct coagulation of juxta-nervous tissue, and functional integrity of the facial nerve, both intraoperatively and postoperatively.

Electrical Pulsed Stimulation of Surfaces Homogeneously Coated with Gold Nanoparticles to Induce Neurite Outgrowth of PC12 Cells

In this study, the potential of gold nanoparticles (20 nm) to deliver electrical stimulation to nerve cell cultures in vitro to induce nerve regeneration was evaluated. In order to use these biomaterials to deliver an electrical stimulus, we devised a novel method for the fabrication of a nanostructured 2D substrate comprising gold nanoparticles attached to the surface of a cover glass via an adsorption system. In this strategy, gold nanoparticles are created and then coated onto a positively charged cover glass that has been pretreated with polyethyleneimine (PEI). Scanning electron microscopy (SEM) revealed that the PC 12 cells extended neurites well on the gold nanoparticles in the presence of electrical stimulation. In addition, the neurite outgrowth of PC12 cells in response to pulsed and constant electrical stimulation was evaluated by live/dead cell determination, by reverse transcriptase polymerase chain reaction (RT-PCR) analysis, as well as by beta-tubulin and NF-200 expression. By electrical stimulation (250 mV for 1 h), PC12 cells with their neurite outgrowth length were highly increased, with a mean diameter of 98.5 microm. However, the neurite outgrowth length without electrical stimulation was approximately 10 approximately 20 microm. Moreover, the alternating current stimulation also showed good viability (<90%), while a high amount of cell death (more than 30%) was observed with constant current stimulation. Thus, the gold nanoparticles with pulsed current stimulation may provide suitable tools for the nerve regeneration using neuronal cells.

Universal serial bus powered and controlled isolated constant-current physiological stimulator

We have developed a compact, isolated, physiological, constant-current stimulator that is powered and controlled by a universal serial bus (USB) interface. The stimulator is designed to be used in ex vivo cardiac experiments but is suitable for a wide variety of settings. The cost and features compare very favorably with commercial stimulators usually used in research and student laboratories. In addition to being USB powered, other novel aspects of our stimulator include the ability to produce large currents, up to 100 mA through a typical 1 kOmega load, by means of a single high-voltage dc-to-dc converter; user-specified variable period, magnitude, and duration of complex monophasic or biphasic sequences; and easy integration via hardware or software into existing experimental setups.

Excito-oscillatory dynamics as a mechanism of ventricular fibrillation

The instabilities associated with reentrant spiral waves are of paramount importance to the initiation and maintenance of tachyarrhythmias, especially ventricular fibrillation (VF). In addition to tissue heterogeneities, there are only a few basic purported mechanisms of spiral wave breakup, most notably restitution. We test the hypothesis that oscillatory membrane properties act to destabilize spiral waves. We recorded transmembrane potential (V(m)) from isolated rabbit myocytes using a constant current stimulation protocol. We developed a mathematical model that included both the stable excitable equilibrium point at resting V(m) (-80 mV) and the unstable oscillatory equilibrium point at elevated V(m) (-10 mV). Spiral wave dynamics were studied in 2-dimensional grids using variants of the model. All models showed restitution and reproduced the experimental values of transmembrane resistance at rest and during the action potential plateau. Stable spiral waves were observed when the model showed only 1 equilibrium point. However, spatio-temporal complexity was observed if the model showed both excitable and oscillatory equilibrium points (i.e., excito-oscillatory models). The initial wave breaks resulted from oscillatory waves expanding in all directions; after a few beats, the patterns were characterized by a combination of unstable spiral waves and target patterns consistent with the patterns observed on the heart surface during VF. In our model, this VF-like activity only occurred when the single cell period of V(m) oscillations was within a specific range. The VF-like patterns observed in our excito-oscillatory models could not be explained by the existing proposed instability mechanisms. Our results introduce the important suggestion that membrane dynamics responsible for V(m) oscillations at elevated V(m) levels can destabilize spiral waves and thus may be a novel therapeutic target for preventing VF.

THE ROLE OF THE INTENSITY OF LOW FREQUENCY ELECTROACUPUNCTURE STIMULATION ON THE MODULATION OF CAPSAICIN-INDUCED EDEMA IN THE RAT PAW. A BLIND CONTROLLED STUDY.

Experimental animal and clinical human data suggest that electroacupuncture (EAP) reduces the release of substance P from sensitive neurons, both at medullar level and in the periphery. Aim of our study is to verify the effect of different intensities of stimulation on edema induced by subcutaneous administration of capsaicin. The study was performed on 72 male Sprague-Dawley rats divided into 4 experimental groups according to the intensity of electrostimulation (5, 10, 50, 70 mA) and a control group. A constant current electrical stimulator delivering positive and negative biphasic wave (duration of one pulse wave complex: 500 microsec; pulse repetition rate: 5/sec) has been used for the stimulation. The lowest intensity of stimulation (5 mA) was effective in the prevention of neurogenic edema. Conversely, higher stimulation intensities, namely 10 and 50 mA, were not effective in reducing edema. Stimulation at 70 mA caused a worsening of edema, probably due to an increased release of substance P in the paw.