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Characteristics of inhibitory effects of serotonin (5-HT)3-receptor antagonists, YM060 and YM114 (KAE-393), on the von Bezold-Jarisch reflex induced by 2-Methyl-5-HT, veratridine and electrical stimulation of vagus nerves in anesthetized rats.

We evaluated the inhibitory effects of YM060 [(R)-5-[(1-methyl-1H-indol- 3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole monohydrochloride] and YM114 (KAE-393) [(R)-5-[(1-indolinyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole monohydrochloride] on the von Bezold-Jarisch reflex (BJR) induced by 2-methyl-5-HT, a selective serotonin (5-HT)3-receptor agonist; veratridine, which stimulates chemoreceptors and baroreceptors; and electrical stimulation of vagal efferent nerves in anesthetized rats. Results were compared with those of ondansetron and granisetron. 2-Methyl- 5-HT (5-160 micrograms/kg, i.v.) and veratridine (100-200 micrograms/kg, i.v.) dose-dependently decreased the heart rate (BJR). YM060, YM114, ondansetron and granisetron dose-dependently inhibited 2-methyl-5-HT (40 micrograms/kg, i.v.)-induced BJR, with ID50 values of 0.012, 0.060, 0.97 and 0.15 microgram/kg, i.v., respectively. Their 5-HT3 receptor blocking potencies against 2-methyl-5-HT-induced BJR were largely consistent with those against 5-HT-induced BJR. In contrast, higher doses (100 micrograms/kg, i.v.) of YM060, YM114, ondansetron and granisetron did not inhibit veratridine (150 micrograms/kg, i.v.)-induced BJR. Atropine (300 micrograms/kg, i.v.) abolished bradycardia induced by electrical stimulation of vagal efferent nerves, whereas YM060, YM114, ondansetron and granisetron had no effect at a dose of 1000 micrograms/kg, i.v. 5-HT (0.625-5.0 micrograms) injected into the left ventricle also caused a dose-dependent decrease in heart rate, an effect that was abolished by YM060 (0.1 microgram/kg, i.v.), atropine (100 micrograms/kg, i.v.) and vagotomy. These results suggest that YM060 and YM114 are highly potent and selective 5-HT3-receptor antagonists that do not affect veratridine- or electrical stimulation-induced bradycardia in anesthetized rats. They also suggest that 5-HT-induced BJR in anesthetized rats originates from 5-HT3 receptors located on the endings of vagal afferent nerves in the heart.

Animals↗

Strength of the quadriceps femoris muscle and functional recovery after reconstruction of the anterior cruciate ligament. A prospective, randomized clinical trial of electrical stimulation.

Immediately after reconstruction of the anterior cruciate ligament, 110 patients were randomly assigned to treatment with high-intensity neuromuscular electrical stimulation (thirty-one patients), high-level volitional exercise (thirty-four patients), low-intensity neuromuscular electrical stimulation (twenty-five patients), or combined high and low-intensity neuromuscular electrical stimulation (twenty patients). All treatment was performed isometrically with the knee in 65 degrees of flexion. All of the patients participated in an intensive program of closed-kinetic-chain exercise. After four weeks of treatment, the strength of the quadriceps femoris muscle and the kinematics of the knee during stance phase were measured. Quadriceps strength averaged 70 per cent or more of the strength on the uninvolved side in the two groups that were treated with high-intensity electrical stimulation (either alone or combined with low-intensity electrical stimulation), 57 per cent in the group that was treated with high-level volitional exercise, and 51 per cent in the group that was treated with low-intensity electrical stimulation. The kinematics of the knee joint were directly and significantly (p < 0.05) correlated with the strength of the quadriceps. There was a clinically and statistically significant (p < 0.05) difference in the recovery of the quadriceps and the gait parameters according to the type of operation that had been performed: the patients who had had reconstruction of the anterior cruciate ligament with use of an autologous patellar-ligament graft did poorly compared with the other patients.

Adult↗

Subcortical electrical stimulation for control of intractable pain in humans. Report of 122 cases (1970-1984).

Chronic electrical stimulation of the subcortical area of the brain by implanted electrodes provides satisfactory control of a number of intractable pain syndromes that are refractory to medication. This series of 122 patients who underwent electrode implantation for the control of severe chronic pain was evaluated over a follow-up period of 2 to 14 years. Of the 65 patients with pain of peripheral origin, who were treated with stimulation of the periaqueductal gray region (PAG), 50 obtained successful pain control. Of 76 patients with a deafferentation pain syndrome, 44 obtained control of the dysesthesia with stimulation of the subcortical somatosensory region. Nineteen patients with both leg and back pain received electrodes in the PAG and the somatosensory regions; whereas back pain was relieved by PAG stimulation, dysesthetic leg pain was controlled more effectively by somatosensory region stimulation. The electrical stimulation technique appears to provide long-term pain control safely, with few side effects or complications.

Adult↗

Analysis of monophasic and biphasic electrical stimulation of nerve.

In an earlier study, biphasic and monphasic electrical stimulation of the auditory nerve was performed in cats with a cochlear implant. Single-unit recordings demonstrated that spikes resulting from monophasic and biphasic stimuli have different thresholds and latencies. Monophasic thresholds are lower and latencies are shorter under cathodic stimulation. Results from stochastic simulations of a biophysical model of electrical stimulation are similar. A simple analysis of a linear, "integrate to threshold" membrane model accounts for the threshold and latency differences observed experimentally and computationally. Since biphasic stimuli are used extensively in functional electrical stimulation, this analysis greatly simplifies the biophysical interpretation of responses to clinically relevant stimuli by relating them to the responses obtained with monophasic stimuli.

Action Potentials↗

Understanding the origin of visual percepts elicited by electrical stimulation of the human retina.

BACKGROUND: The success of a retinal prosthesis for patients with outer retinal degeneration (ORD) depends on the ability to electrically stimulate retinal cells other than photoreceptors. Experiments were undertaken in human volunteers to ascertain whether electrical stimulation of cells other than photoreceptors will result in the perception of light. METHODS: In two subjects, two areas of laser damage (argon green and krypton red) were created in an eye scheduled for exenteration due to recurrent cancer near the eye. In the operating room prior to exenteration, under local anesthesia, a hand-held stimulating device was inserted via the pars plana and positioned over the damaged areas and normal retina. Subjects' psychophysical responses to electrical stimulation were recorded. RESULTS: In both subjects, electrical stimulation produced the following perceptions. Normal retina: dark oval (subject 1), dark half-moon (subject 2); krypton red laser-treated retina: small, white light (both subjects); argon green laser treated retina: thin thread (subject 1), thin hook (subject 2). Histologic evaluation of the krypton red-treated retina showed damage confined to the outer retinal layers, while the argon green-treated area evinced damage to both the outer and the inner nuclear layers. CONCLUSION: The perception produced by electrical stimulation was dependent on the retinal cells present. Electrical stimulation of the krypton red-ablated area best simulated the electrically elicited visual perceptions of our blind, ORD patients, suggesting that the site of stimulation in blind patients is the inner retinal neurons.

Aged↗

Electrical stimulation as a therapeutic option to improve eyelid function in chronic facial nerve disorders.

PURPOSE: To establish whether it is possible to improve orbicularis oculi muscle function in the eyelids of patients with a chronic seventh cranial nerve palsy by using transcutaneous electrical stimulation to the point at which electrical stimulation induces a functional blink. METHODS: Ten subjects (one woman, nine men) aged 36 to 76 with chronic, moderate to severe facial nerve palsy were recruited into the study. Voluntary and spontaneous eyelid movements were assessed, using an optical measuring system, before, during, and after a 3-month treatment period. Voluntary and spontaneous lid velocities were also measured and compared with eyelid kinematic data in normal subjects (12 women, 18 men; age range, 22-56 years). RESULTS: Therapeutic electrical stimulation applied over 3 months produced improvement in eyelid movement (>2 mm) in 8 of 10 patients during voluntary eyelid closure. However, there was no significant improvement recorded in spontaneous blink amplitudes or peak downward-phase velocity of the upper eyelid. This regimen of stimulation failed to recover function well enough that a functional blink could be induced in the paretic eyelid by electrical stimulation. CONCLUSIONS: Electrical stimulation using transcutaneous electrical nerve stimulators units can improve voluntary eye closure, apparently because of a reduction in stiffness of eyelid mechanics, rather than an improvement of muscle function. Investigation of alternative stimulation regimens is warranted.

Adult↗

Gastric electrical stimulation in medically refractory nausea and vomiting.

INTRODUCTION: High-frequency gastric electrical stimulation is a new therapeutic option to improve refractory nausea and vomiting, in gastroparetic patients. Its effects on gastric emptying are, however, inconstant and limited. Therefore, we have hypothesized that high-frequency gastric electrical stimulation could be also effective in patients suffering from refractory vomiting and nausea with normal gastric emptying, and we have compared the symptomatic efficacy of high-frequency gastric electrical stimulation between patients with delayed and normal gastric emptying. PATIENTS AND METHODS: Fifteen patients with chronic, severe and medically resistant nausea and vomiting were included in the study. Gastric emptying was delayed in eight patients (Group 1) and normal in seven patients (Group 2). At inclusion and at 6 months after the start of the stimulation, symptoms (nausea and vomiting, bloating, regurgitations, abdominal pain and appetite) and quality of life were prospectively evaluated using the Gastrointestinal Quality of Life Index score whereas gastric emptying was assessed by scintigraphy and/or octanoic acid breath test. RESULTS: Age, sex, symptoms and quality of life were not different at baseline between the two groups. At 6 months, Gastrointestinal Quality of Life Index and nausea/vomiting scores had significantly improved in both groups. Other symptoms (bloating, regurgitations, abdominal pain and appetite) had improved at 6 months in Group 1 but not in Group 2. Six months after the start of stimulation, gastric emptying was normal in 4/8 Group 1 patients and 5/7 Group 2 patients but was not significantly different from that calculated before the implantation of the stimulator. CONCLUSION: Our results suggest that high-frequency gastric electrical stimulation could be an effective therapy for treating chronic, severe vomiting and nausea whether gastric emptying is delayed or not.

Adult↗

Electrical stimulation of the midbrain tectum enhances dopamine release in the frontal cortex.

One widely used animal model of anxiety is the electrical stimulation of a given structure supposed to be involved in the neural circuitry underlying emotional behavior. Indeed, electrical stimulation of midbrain structures with substrates for the processing of fear-like responses, such as the dorsal periaqueductal gray matter (DPAG) or the inferior colliculus (IC), produces behavioral, sensorial and autonomic responses very similar to the defense reactions observed in environmental threatening situations. It has also been proposed that the required level of integration of all these components of the defense reaction needs an integrative process situated at higher brain level, as the prefrontal cortex. As a matter of fact, substantial cortical inputs to the midbrain tectum have already been found. In view of this evidence, it seems important to know whether animals stimulated in the midbrain tectum would present neurochemical changes in the prefrontal cortex. To this end, we examined the temporal course of the effects of the electrical stimulation of the DPAG and IC on the dopamine (DA) release in the prefrontal cortex. Electrical stimulation of these structures was performed at the alertness (control) and escape thresholds. Electrical stimulation of the inferior colliculus at the escape threshold produced a long-lasting increase in the levels of corticofrontal dopamine in relation to these measurements in the control group. No significant changes in extracellular DA release in this cortical area could be observed following DPAG electrical stimulation. These findings bring evidence for the involvement of dopamine of the frontal cortex in the setting up of adaptive responses to stressful situations generated at the inferior colliculus level.

3,4-Dihydroxyphenylacetic Acid↗

Exacerbation of a case of myasthenia gravis during therapeutic electric stimulation.

In patients with myasthenia gravis, vigorous exercise and electric stimulation produce weakness that is usually reversed by rest. We describe a case of persistent weakness in a 31-year-old woman with myasthenia gravis following therapeutic electric stimulation. She was injured in an automobile accident, with cervical and lumbar muscle strain diagnosed by a local emergency room physician. She consulted a chiropractor two days later because her symptoms had not abated. The chiropractic treatment of short-wave diathermy, high-voltage electric stimulation and spinal manipulation continued thrice weekly for six weeks. She then presented to her neurologist, complaining of persistent fatigue, weakness, increased diplopia, cervical and occipital pain, and disrupted sleep. Neck weakness had developed since her last visit. She was admitted to the hospital for evaluation. Neurologic exam showed no other abnormality of strength, sensation, or reflexes. The exacerbation of myasthenia responded to prednisone and increased pyridostigmine. After two months she required only her preinjury dose of pyridostigmine (60 mg q.d. p.r.n.) to prevent diplopia or fatigue, and her strength was normal. Repeated electrically induced muscle contraction is suspected of causing this exacerbation of myasthenia gravis.

Adult↗

Epidural spinal electrical stimulation in severe angina pectoris.

The short term effects of epidural spinal electrical stimulation were studied in 10 patients with angina pectoris of New York Heart Association functional class III or IV. The antianginal pharmacological treatment given at entry to the study was regarded as optimal and was not changed during the study. The effects of epidural spinal electrical stimulation were measured by repeated bicycle ergometer tests. Treatment with epidural spinal electrical stimulation increased the patients' working capacity, decreased ST segment depression, increased time to angina, and reduced the recovery time. The observed effects did not seem to be correlated with any changes in myocardial oxygen demand during epidural spinal electrical stimulation and were additional to the benefits of the pharmacological treatment.

Aged↗

Broad applicability of ultrarapid train stimulation as an efficient alternative to conventional programmed electrical stimulation.

BACKGROUND AND STUDY OBJECTIVE: Conventional programmed electrical stimulation (PES) is useful for establishing inducibility or noninducibility of clinical ventricular arrhythmias (VA), but is complex and time-consuming. This study compared a standard PES protocol with ultrarapid train stimulation (UTS) in a broad range of patients with and without a history of ventricular arrhythmias or structural heart disease. METHODS: Patients prospectively underwent electrophysiologic testing with both UTS and conventional PES protocols in a randomized, crossover design. RESULTS: The results were concordant in 79% of 150 matched pairs of comparisons in 104 patients (NS). There were no differences related to underlying heart disease or arrhythmia, or antiarrhythmic treatment. Induction of nonclinical arrhythmias with the two methods was similar (P = 0.524). Inhibition phenomena were minor except in some patients receiving amiodarone. Fewer drive-extrastimuli sequences and less time were needed to complete the trains protocol (P < 0.0001). CONCLUSIONS: In cases where the main intent is to induce ventricular arrhythmias, UTS yields results that are similar to those of conventional PES protocols in a shorter length of time.

Anti-Arrhythmia Agents↗

Electrically conductive biodegradable polymer composite for nerve regeneration: electricity-stimulated neurite outgrowth and axon regeneration.

Normal and electrically stimulated PC12 cell cultures and the implantation of nerve guidance channels were performed to evaluate newly developed electrically conductive biodegradable polymer composites. Polypyrrole (PPy) doped by butane sulfonic acid showed a significantly higher number of viable cells compared with PPy doped by polystyrenesulfonate after a 6-day culture. The PC12 cells were left to proliferate for 6 days, and the PPy-coated membranes, showing less initial cell adherence, recorded the same proliferation rate as did the noncoated membranes. Direct current electricity at various intensities was applied to the PC12 cell-cultured conductive membranes. After 7 days, the greatest number of neurites appeared on the membranes with a current intensity approximating 1.7-8.4 microA/cm. Nerve guidance channels made of conductive biodegradable composite were implanted into rats to replace 8 mm of sciatic nerve. The implants were harvested after 2 months and analyzed with immunohistochemistry and transmission electron microscopy. The regenerated nerve tissue displayed myelinated axons and Schwann cells that were similar to those in the native nerve. Electrical stimulation applied through the electrically conductive biodegradable polymers therefore enhanced neurite outgrowth in a current-dependent fashion. The conductive polymers also supported sciatic nerve regeneration in rats.

Absorbable Implants↗

Effects of intermittent electrical stimulations on muscle catabolism in intensive care patients.

To determine whether muscular contractions obtained by electrical stimulation in immobilized patients are able to reduce muscle catabolism, we studied 10 patients (65-79 yr old) hospitalized in the intensive care unit for postoperative ventilatory failure or cerebral infarction. Artificial nutrition was the same for each patient during the 9-day study period. Two periods of 4 days were defined and randomized for each patient, separated by one day. During the muscular stimulation (MS) period, intermittent electrical stimulation of the muscles of the legs (external electrodes), were performed daily during 2 X 30 mn. During the other period, muscular stimulations were not performed. Urinary excretion of nitrogen (micro-Kjeldhal digestion and Nessler procedure), creatinine (Jaffe reaction), and 3-methyl histidine (3-MH) (gas phase chromatography) was measured every day. (table; see text) We conclude that a significant decrease in 3-MH and creatinine excretion is observed during the MS period. In intensive care unit patients, muscle protein breakdown may be influenced by intermittent muscular electrical stimulation.

Aged↗

In vivo evaluation of coralline hydroxyapatite and direct current electrical stimulation in lumbar spinal fusion.

STUDY DESIGN: An animal model of posterolateral intertransverse process lumbar spinal fusion using autologous bone, coralline hydroxyapatite, and/or direct current electrical stimulation. OBJECTIVES: To evaluate the effect of an osteoconductive bone graft substitute and direct-current electrical stimulation on the rate of pseudarthrosis in a rabbit spinal fusion model. SUMMARY OF BACKGROUND DATA: Conventional techniques for the surgical treatment of degenerative conditions in the lumbar spine have a substantial failure rate and associated morbidity. Bone graft substitutes and electrical stimulation are alternative techniques to enhance fusion rates and limit the morbidity associated with posterolateral intertransverse process fusion using autologous iliac crest bone graft. METHODS: Fifty-three adult female New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were assigned to one of four groups using either autologous bone (Group I), coralline hydroxyapatite with autologous bone marrow aspirate (Group II), coralline hydroxyapatite with a 40-microA implantable direct current electrical stimulator and bone marrow aspirate (Group III), or coralline hydroxyapatite with a 100-microA implantable direct current electrical stimulator and bone marrow aspirate (Group IV). Animals were killed at 8 weeks, and fused motion segments were subjected to manual palpation, mechanical testing, and radiographic and histologic analysis to assess the fusion mass. RESULTS: Successful fusion was achieved in 57% (8/14) of animals in Group I, 25% (3/12) in Group II, 50% (6/12) in Group III, and 87% (13/15) in Group IV. Mean stiffness and ultimate load to failure were significantly higher in Group IV than in all other groups (P < 0.05). Histologic analysis demonstrated a qualitative increase in fusion mass in Group IV versus all other groups. CONCLUSIONS: Direct-current electrical stimulation increased fusion rates in a dose-dependent manner in a rabbit spinal fusion model. Coralline hydroxyapatite is an osteoconductive bone graft substitute, and thus requires an osteoinductive stimulus to ensure reliable fusion rates. Furthermore, coralline hydroxyapatite and direct current electrical stimulation can be used together to increase fusion rates in a rabbit spinal fusion model while avoiding the morbidity associated with harvesting iliac crest bone.

Animals↗

Inhibition of ovulation in the rat by electrical stimulation of the lateral amygdala.

Effects of electrical stimulation of the lateral amygdaloid areas on ovulatory gonadotropin release were examined in adult Wistar female rats. Electrical stimulation was applied in rats in proestrus under ether anesthesia with square wave pulses of 0.5 ms duration and 100 Hz frequency for 30 min (30 sec on and off). Stimulation of the lateral amygdala blocked ovulation in 50% of animals when it was applied between 13:30 and 14:30 with a current of 300 muA. Stimulation of the medial amygdala under the same experimental condition was absolutely ineffective to block ovulation. Sham stimulation was also ineffective. In determining the gonadotropin concentration in serum, the stimulation into the lateral amygdala was observed to inhibit the ovulatory release of LH, FSH and prolactin. It may be said that the lateral amygdaloid area participates in the control of gonadotropin release in an inhibitory manner.

Amygdala↗

[The effects of electrical stimulation on epiphyseal cartilage].

The effects of electrical stimulation on epiphyseal growth were studied. The epiphyseal cartilage of the proximal tibia of New Zealand white rabbits was stimulated by direct current for 2 weeks. A constant direct current of 5 microA was supplied by an electrical stimulation system buried under the subcutaneous tissue. Contralateral tibia with dummy electrodes served as control. The results were as follows: The height of the epiphyseal plate near the electrodes was slightly increased by traumatic reaction to the electrodes in the control group. However, in the stimulation group, the height was more remarkably increased than in the control group. The height of the epiphyseal plate was 0.6 +/- 0.2 mm in the control group, and 1.0 +/- 0.4 mm in the stimulation group, showing a statistical difference. The mineral appositional rate, determined by tetracycline labels, was 3.0 +/- 0.8 microns/day in the control group and 4.6 +/- 0.4 microns/day in the stimulation group. It was observed that the turnover of the epiphyseal plate was accelerated in the stimulation group, but no other abnormal findings were observed by electron microscopy. In conclusion, it is clear that growth of the epiphyseal cartilage is accelerated by direct current.

Animals↗

The treatment of urinary incontinence with electrical stimulation in nursing home patients: a pilot study.

OBJECTIVES: To test the effectiveness of electrical stimulation in the treatment of urinary incontinence in female nursing home patients. SETTING: A community long term care facility. PARTICIPANTS: Nine unselected female nursing home patients with urinary incontinence. All patients were moderately to severely cognitively impaired. By bedside cystometry, six patients had involuntary detrusor contractions while two had inconclusive results. INTERVENTION: Participants were treated with electrical stimulation for 8 weeks using the Microgyn II device. A current with a frequency of 20 hertz and a pulse width of 1 millisecond was delivered repeatedly for 2 seconds on, 4 seconds off for 15 seconds twice a week. MEASUREMENTS: The number of every-2-hour wet episodes during a 48-hour period (Wet) was recorded by a blinded observer at baseline and after 4 and 8 weeks of treatment. We evaluated the overall effect of electrical stimulation by averaging the Wet at 4 and 8 weeks for each patient and comparing it to Wet at baseline. MAIN RESULTS: The mean +/- standard deviation of intensity of electrical stimulation was 12 +/- 5 milliamps. Mean Wet at baseline was 11.8 +/- 4.2. For all patients mean Wet increased by 2.3 +/- 3.2, P = 0.07. Analysis of patients with documented involuntary detrusor contractions showed a mean increase in Wet of 2.6 +/- 3.6, P = 0.16. The volume of fluid at which an involuntary contraction occurred during cystometry showed a mean increase of 48.3 +/- 52.6 mL, P = 0.07 after 8 weeks of treatment. CONCLUSIONS: Electrical stimulation is well tolerated in elderly nursing home patients. However, it was ineffective in improving urinary incontinence. In fact, there was a tendency for the treatment to worsen the incontinence.

Aged↗

Augmenting voluntary torque of healthy muscle by optimization of electrical stimulation.

The purpose of this study was to evaluate the ability of electrical stimulation (2,500-Hz sine waves, interrupted for 50 pulsed bursts per second) to improve muscle torque using low-dosage training characteristics. Fifteen healthy subjects (9 men, 6 women), 20 to 32 years of age, participated in the experiment. All subjects received electrical stimulation of the right anterior thigh musculature while their left leg served as the control. Electrical stimulation was repeated eight times per session, each stimulation producing isometric torque equal to 50% of the subject's maximum voluntary isometric contraction. The sessions were repeated twice a week over a period of five weeks. Results showed that electrical stimulation, when used with the specified low-dosage training characteristics of this study, will augment quadriceps femoris muscle torque of men.

Adult↗