Intravesical Electrical Stimulation Research Articles

Efficacy in Using Urodynamic Parameters of Intravesical Electrical Stimulation for Detrusor Underactivity.

Intravesical electrical stimulation (IVES) remains a controversial therapy for detrusor underactivity (DUA). The purpose of this study is to determine the efficacy of IVES in patients with DUA using pre- and post-IVES urodynamic parameters. Intravesical electrical stimulation procedure is performed using a specific catheter equipped with an internal electrical electrode (cathode). The anode is subsequently affixed to the lower abdomen (suprapubic). Afterward, this specialized catheter is connected to a stimulator. Patients undergo a series of 12 IVES procedures in 1 month with the following predetermined parameters: 20 mA amplitude, 20 Hz frequency, 200 µs pulse width, and 60 minutes stimulation time. Patients underwent a follow-up urodynamic examination 1 month after the IVES series is completed. After IVES, several notable changes were observed, including an increase in Qmax from 7.28 ± 5.24 to 7.29 ± 4.09 (P=.030), a decrease in post-void residual (PVR) from 73.03 ± 43.91 to 62.07 ± 39.10 (P=.005), and an increase in PDet@tQmax from 17.10 ± 12.35 to 18.87 ± 12.47 (P=.009). The aetiologies of DUA were categorized into 3 groups: chronic obstruction (CO), idiopathic (Idio), and neurological disorder (ND). The CO group exhibited significant changes in urodynamic parameters, specifically Qmax (P=.001), PVR (P=.001), and PDet@Qmax (P=.035). Similarly, the idiopathic group also demonstrated improvements in Qmax (P=.008), PVR (P=.037), and PDet@ Qmax (P=.033). Intravesical electrical stimulation has been shown to have a positive effect on patients diagnosed with DUA, particularly those whose DUA is idiopathic or due to chronic obstruction.

Intravesical Electrical Stimulation Improves Abnormal Prefrontal Brain Activity in Patients With Underactive Bladder: A Possible Central Mechanism.

The aim of this study was to explore the mechanisms of central brain action in patients with neurogenic underactive bladder (UAB) treated with intravesical electrical stimulation (IVES). We prospectively recruited patients with neurogenic UAB who chose to receive IVES treatment and healthy subjects (HS). At baseline, the following data were obtained: a 72-hour voiding diary; measurements of postvoid residual urine (PVR), voiding efficiency (VE) and first sensation of bladder filling (FS); American Urological Association Symptom Index Quality of Life (AUA-SI-QOL) scores, and functional near-infrared spectroscopy scans of the prefrontal cortex in the voiding stage. All UAB patients were re-evaluated for these indices after completing 4 weeks of IVES. A >50% improvement in PVR was defined as successful IVES treatment. Prefrontal activity was analyzed using the NIRS_KIT software, corrected with the false discovery rate (P<0.05). Statistical analysis was performed using IBM SPSS Statistics ver. 22.0, and P<0.05 was considered statistically significant. Eighteen UAB patients and 16 HS were included. IVES treatment was successful in 11 UAB patients and failed in 7. The PVR, VE, 24-hour clean intermittent catheterization, FS volume, and AUA-SI-QOL scores of the UAB group significantly improved after successful IVES treatment. BA9 (right dorsolateral prefrontal cortex [DLPFC]) and BA10 (right frontal pole) were significantly activated after successful IVES, and no significant difference was found between the successful group and HS group after IVES. Before IVES, BA10 (right frontal pole) was significantly deactivated in the failed group compared with the successful group. The possible central mechanism of IVES treatment for neurogenic UAB is that IVES reactivates the right DLPFC and right frontal pole.

Effects of Intravesical Electrical Stimulation on Urinary Adenosine Triphosphate and Nitric Oxide in Rats With Detrusor Underactivity Induced By Bilateral Pelvic Nerve Crush Injury: The Possible Underlying Mechanism.

To explore the effect of intravesical electrical stimulation (IVES) on urinary adenosine triphosphate (ATP) and nitric oxide (NO) in rats with detrusor underactivity (DU) induced by bilateral pelvic nerve crush (bPNC), and to determine the underlying peripheral mechanism. Twenty-four female Sprague-Dawley rats were equally divided into 3 groups: sham; bPNC; and IVES. Rats in the IVES group began to receive IVES treatment 10 days after bPNC (20 minutes per day for 14 consecutive days). After the 14th IVES, rat urine was collected and cystometry was performed. The serum creatinine, blood urea nitrogen, and urinary ATP and NO levels were measured, and a routine urinalysis was performed. The maximum cystometric capacity (MCC), maximum changes in bladder pressure during filling (∆FP), and postvoid residual urine (PVR) in the IVES group were significantly lower than the bPNC group, and the maximum changes in bladder pressure during voiding (∆VP) was significantly higher than the bPNC group. Compared with the sham group, the MCC, ∆FP and PVR were significantly increased, and the maximum voiding pressure (MVP) and ∆VP were significantly decreased in the bPNC group. After bPNC, urinary ATP was significantly decreased, and urinary NO was significantly increased. In IVES-treated rats, urinary ATP was significantly higher than the bPNC group, and NO was significantly lower than the bPNC group. In addition, the ATP-to-NO ratio of the rats in the bPNC group was significantly lower than the sham and IVES groups. Correlation analysis showed that the ATP and NO were not correlated with the MCC, ∆FP, MVP, ∆VP, and PVR. Promoting the release of urothelial ATP and inhibiting the release of urothelial NO may be one of the peripheral mechanisms underlying IVES in the treatment of DU. Specifically, IVES may shift the balance between excitation and inhibition toward excitation.

Randomized controlled trial of intravesical electrical stimulation for underactive bladder.

To evaluate the efficacy and safety of intravesical electrical stimulation (IVES) performed with a novel device in patients with underactive bladder (UAB). This was a multicentre, prospective, single-blind, randomized controlled clinical trial of patients with UAB in China. Eligible patients were randomly assigned in a 1:1 ratio to receive conventional IVES (n = 38) or IVES with an open circuit (n = 38). The primary efficacy measure was change from baseline in post-void residual urine volume (PVR) after 4 weeks of treatment. Secondary efficacy measures included changes in maximum urinary flow rate (Qmax ), bladder voiding efficiency (BVE), number of 24-h clean intermittent catheterization (CIC) procedures, and Patient Perception of Bladder Condition-Scale (PPBC-S) and American Urological Association Symptom Index Quality of Life (AUA-SI-QoL) scores from baseline after 4 weeks of treatment. Adverse events (AEs) were monitored throughout the trial. In the full analysis set (FAS), the mean (sd) PVR changes in the trial and control groups at 4 weeks were -97.1 (107.5) mL and -10.5 (86.7) mL, respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -102.9 (100.0) mL vs 0.7 (82.5) mL (P < 0.01). In the FAS and PPS, Qmax improved significantly at 4 weeks (P = 0.04 and P = 0.03). In the FAS and PPS, BVE was significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas no significant differences in the number of 24-h CIC procedures, PPBC-S score or AUA-SI-QoL score were observed between the groups. Six possible therapy-related AEs occurred in six patients (four in the trial group and two in the control group; P = 0.67), all of which were urinary tract infections. No severe AEs were reported. The results of this clinical study strongly demonstrate that UAB patients benefit from this novel IVES device. More research is needed to validate the clinical utility of this device.

Neuromodulation possibilities in neurogenic lower urinary tract dysfunction

Introduction. Neuromodulation has proven itself in the treatment of patients suffering from idiopathic overactive bladder and non-obstructive urinary retention, who are resistant to conservative therapy. The possible use of the method in the population of patients with neurogenic lower urinary tract dysfunction (NLUTD) is of undoubted clinical interest.Objective. To analyze the current possibilities and features of neuromodulation in a cohort of patients with NLUTD.Materials and methods. Original research materials published in the PubMed, eLibrary, SciVerse (ScienceDirect), Scopus, Medline, EMBASE databases, websites of professional associations without restrictions on the date of publication were used. Sixty sources were selected for citation, with preference given to systematic reviews, meta-analyses and RCTs .Results. In relation to NLUTD, transcranial and peripheral magnetic stimulation, intravesical electrical stimulation, tibial, pudendal electrical stimulation, and stimulation of the dorsal pudendal nerve, as well as sacral and epidural methods of neurostimulation are considered.Conclusion. The current literature optimistically presents the experience of using neuromodulation in the NLUTD patient population with the largest evidence base for invasive sacral and tibial stimulation. The studies are based on heterogeneous populations, limited by small sample sizes with insufficient descriptive part of the degree and severity of neurological diseases, and it should be considered when forming guidelines. However, the lack of other suitable therapies and promising initial results indicate the importance of further efforts to improve the applied methods of neuromodulation. Further studies are needed with larger sample sizes, better classification of diseases, and controlled study design

Low-Frequency Intravesical Electrical Stimulation for the Treatment of Acute Urinary Retention: A Promising Therapeutic Approach.

Acute urinary retention (AUR) is a troublesome urological disease, which causes various lower urinary tract symptoms. However, only few studies explored and evaluated the effective treatments to improve AUR. We aimed to find an effective approach to cure AUR through comparing the efficacy of existing classical low-frequency transcutaneous electrical nerve stimulation (TENS) and novel intravesical electrical stimulation (IVES). A total of 24 AUR female rats were divided into 3 groups as follows: control, TENS, and IVES groups. Rats in the control group had no fake stimulation. Rats in the TENS and IVES groups underwent transcutaneous or intravesical stimulation of a symmetrical biphasic rectangular current pulse with a frequency of 35 Hz, 30 min per day, for seven consecutive days. IVES significantly reduced the actin expression in the submucosal layer but increased its expression in the detrusor layer (p = 0.035, p = 0.001). The neovascularization in the submucosal layer in the IVES group was significantly increased than in the other 2 groups (p = 0.006). Low-frequency IVES performed better than TENS in terms of simultaneously relieving bladder hyperactivity, accelerating epithelial recovery, and strengthening detrusor muscle. IVES may be a promising therapeutic approach for bladder dysfunction, specifically for AUR and overactive bladder in clinical practice.

Neuromodulation of the Pudendal Nerve Assisted by 3D Printed: A New Method of Neuromodulation for Lower Urinary Tract Dysfunction

Electrical stimulation of peripheral nerves by implanted electrodes is an effective treatment for certain pelvic floor diseases. As well as intravesical electrical stimulation, this predominantly includes stimulation of the sacral nerve, tibial nerve, and pudendal nerve. The pudendal nerve is one of the main nerves that stimulate pelvic floor muscles, external urethral meatus, and the anal sphincter and pelvic organs, and it may have effects on frequent urination, urgency, dysuria, and perineal pain. It is difficult to locate because of its anatomical course, however, leading to difficulties fixing the electrode, which increases the difficulty of pudendal nerve electrical stimulation in clinical practice. In the current study 3D printed navigation was used to solve these problems. Combined with autopsy data and patient pelvic and nerve data, a personalized design was generated. Neural modulation of the pudendal nerve was achieved by implanting the lead with the guidance of 3D printed navigation. 3D printed navigation can maximize the phase II conversion rate, reduce the difficulty of surgery, shorten the operation time, reduce damage to additional organs and blood vessels, and increase the accuracy of electrode implantation, and it can be performed while the patient is awake. It is an accurate, reversible, efficient, and minimally invasive surgery.

A systematic review of clinical studies on electrical stimulation therapy for patients with neurogenic bowel dysfunction after spinal cord injury

This study aimed to perform a systematic literature review of the clinical trial evidence on electrical stimulation for the treatment of neurogenic bowel dysfunction (NBD) after spinal cord injury (SCI). Systematic electronic searches were carried out in the PubMed/Medline, EMBASE, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure databases, along with the reference lists in the include studies. Studies were eligible for inclusion if they adopted a controlled clinical design based on human population, the patients suffered from spinal cord injury, the main outcomes were the disorders of bowel function and the intervention was electrical stimulation. Also, the language was limited to English and Chinese. Eleven studies were included in this systematic review, comprising transcutaneous electrical stimulation, transrectal bowel stimulation, sacral nerve stimulation, intravesical electrical stimulation, etc. Of the 11 studies, 3 were randomized controlled trials, 8 were controlled before-and-after trials. The quality of the included studies was moderate bias risk. Most studies revealed that the electrical stimulation was beneficial for the patient with NBD after SCI. Only 11 small clinical studies with 298 participants have evaluated the efficacy of electrical stimulation for NBD after SCI. Although some studies showed electrical stimulation was benefit for the patient with NBD after SCI, there was currently not enough evidence to support the use of electrical stimulation could improve the clinical symptoms of those patients. Thus, well-designed randomized controlled trials with larger patient population are warranted to establish its benefit in clinical practice in the future.

Repeat periods of electrical stimulation prolong the modulation of the micturition reflex in the rat.

The aim of this study was to determine if the duration of the micturition reflex modulation could be prolonged by repeated periods of afferent stimulation in the decorticated rat. Eighteen female Sprague-Dawley rats were used for the study, 10 for intravesical electrical stimulation (IVES), and 8 for Ano-genital pudendal afferents stimulation. Repeated constant flow cystometries were performed with body-warm saline (0.06-0.1 mL/min) at about 10 min interval. The selected afferents were stimulated continuously for 5 min at maximal intensity. The same stimulation was repeated six times with a pause of 5 min between the stimulations. The mean threshold volume of cystometries performed during one hour before and each hour after the stimulation were compared. After six periods of IVES, the micturition threshold volume decreased to its lowest value (62% of control) during the first hour and remained at 80% 4 h later (n = 10, P < 0.01). Ano-genital afferent stimulation produced a corresponding increase in the micturition threshold volume. The long-lasting poststimulation effect was again observed for more than 5 h. During the first hour the mean threshold volume increased to 211% of controls and it remained at about this level for the entire observation period (n = 8, P < 0.01). Repeated short periods of stimulation prolonged the modulatory effect well beyond the stimulation period. The findings provide experimental evidence supporting the clinical application of IVES and ano-genital stimulation for treatment of neurogenic urinary bladder dysfunction.

Intravesical electrical stimulation treatment for overactive bladder: An observational study.

PurposeIntravesical electrical stimulation treatment (IVES) has been successfully used to treat neurogenic bladder. We report the results of an observational study regarding the use of IVES for women with overactive bladder syndrome (OAB) and/or urgency urinary incontinence (UUI).Materials and MethodsIVES was performed in women with OAB (defined by frequency ≥8/day, nocturia ≥2/night, or ≥3 episodes of UUI on 3-day voiding diary) who failed prior medical therapy. Subjects underwent 4 weeks of treatment with an 8-Fr Detruset™ IVES catheter. Primary outcome was Patient Global Impression of Improvement (PGI-I) at 3 months. Secondary outcomes included Visual Analog Scale (VAS), Short Form OAB Questionnaire (OAB-q SF), Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ), reduction in frequency and UUI on voiding diary, and adverse effects. Analysis was done with paired t-tests and Wilcoxon signed rank tests.ResultsSeventeen subjects completed the study. At 4 weeks post-treatment, 15 improved on PGI-I (11 subjects: ‘a little better’, 2: ‘much better’, 2: ‘very much better’). There were significant improvements in symptom bother and health-related quality of life as measured by OAB-q SF and pelvic organ prolapse and urinary distress as measured by PFDI. Frequency decreased from 10.3±4.3 at baseline to 8.9±2.3 (p=0.04) at 3 months. No pain was reported during treatment. There was one urinary tract infection during the study period. No other adverse events were reported.ConclusionsIVES appears to be a safe and effective novel treatment for OAB. Larger comparative studies are needed to investigate its potential for long-term treatment.

Clinical efficacy of intravesical electrical stimulation on detrusor underactivity: 8 Years of experience from a single center.

The aim of this study was to retrospectively evaluate the effectiveness of intravesical electrical stimulation (IVES) on detrusor underactivity (DU).From 2009 to 2016, a total of 105 patients with symptoms of DU who were treated with IVES were included in this retrospective study. The medical records, physical examination findings, urine culture results, and video-urodynamic studies were reviewed. Changes in post-void residual urine (PVR) and voiding efficiency (VE) were included for evaluation of efficacy. Patients achieving a >50% reduction in the PVR were regarded as responders. A >80% reduction in the PVR was considered obvious improvement. A questionnaire was administered to patients with bladder sensation.Of the 105 patients, the information of residual urine volume and voiding volume was obtained in 89 patients, and detailed pre- and post-IVES bladder sensation information was available on 96 patients. Of the 89 patients, 47.2% (42/89) were responders and achieved a >50% reduction in the PVR. Obvious improvement in the PVR, defined as a >80% reduction, occurred in 27% (24/89) of the patients. VE developed in 76.4% (68/89) of the patients, and 30.3% (27/89) of the patients increased >50%. Significant improvements in the PVR and VE were observed during IVES treatment (P < .05). Based on the questionnaire, bladder sensation developed and was sustained in 44.8% (43/96) of the patients.IVES provides a promising method for improving the PVR and VE in a majority of patients with DU. Thus, IVES is worth to further study and carry out.

Electroneurostimulation for the management of bladder bowel dysfunction in childhood.

Both non-invasive and invasive electroneurostimulation (ENS) modalities for bladder bowel dysfunction have been studied and reported in children. A summary of the proposed mechanism of actions and the more commonly used and recently reported techniques and outcomes are described. This includes transcutaneous electrical nerve stimulation, functional electrical nerve stimulation, intravesical electrical nerve stimulation, percutaneous tibial nerve stimulation and sacral neuromodulation in conditions including overactive bladder, enuresis, dysfunctional voiding, constipation, combined bladder bowel dysfunction and neuropathic bladder and bowel dysfunction. There is a need for further high quality randomised trials as well as long-term outcomes to establish whether ENS is able to alter the long-term trajectory for an individual child with bladder bowel dysfunction.

Underactive Bladder and Detrusor Underactivity: a Review of Pathophysiology and Management Strategies for This Poorly Understood Bladder Syndrome

The International Continence Society (ICS) defines underactive bladder (UAB) as a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span. UAB is observed in many conditions and is not just part of normal aging process. Patients with UAB have a diminished sensation of when the bladder is full and are unable to contract the muscles sufficiently to empty the bladder completely. Urodynamic study is currently the only definitive method of assessing detrusor contractile function. Conservative strategies include scheduled void, straining to void, and the use of indwelling/intermittent catheterization. The current pharmacotherapy aims at decreasing the bladder outlet and promoting bladder contractility, while neuromodulation and intravesical electrical stimulation may play a role in selected patients. Future therapy in UAB is likely stem cells regenerative technology, and gene therapy in bladder regeneration and return of normal bladder contractility.

Effects of intravesical electrical stimulation therapy on urodynamic patterns for children with spina bifida: A 10-year experience

ObjectiveIntravesical electrical stimulation (IVES) has been performed for various purposes in children with a neurogenic bladder. We evaluated the results of IVES on urodynamic study parameters in children with spina bifida. MethodsWe retrospectively analyzed the cases of 88 children who received IVES between August 1999 and May 2010 and whose comparative urodynamic data were available before and after treatment. According to the pre-IVES urodynamic study, children were divided into 3 groups: detrusor overactivity, detrusor underactivity and acontractile detrusor. We investigated the changes in detrusor function, bladder capacity and detrusor-sphincter dyssynergia. ResultsIn the group showing detrusor overactivity, the bladder had a synergic pattern in 41.7%, and normal detrusor function was observed in 16.7% of them. Bladder capacity increased after IVES therapy, especially in those who started therapy before 18 months of age (p = 0.019). Detrusor-sphincter dyssynergia was resolved in 55.6%. In the acontractile detrusor group, detrusor contraction ability increased in 48%, but bladder capacity did not. ConclusionsAppropriate candidates for this treatment need to be carefully selected.

Cause of Residual Urine in Bladder Outlet Obstruction: An Experimental Study in the Rat

We explored the role of bladder mechanoreceptors in post-void residual urine in rats with bladder outlet obstruction. Partial bladder outlet obstruction was induced by a urethral ligature in 11 adult female Sprague-Dawley® rats. Nine sham operated rats served as controls. The outcome was evaluated in acute experiments using α-chloralose anesthesia 6 weeks later. Bladders were catheterized for infusion, pressure recording and intravesical electrical stimulation. Bladder efferent activity was recorded from a thin pelvic nerve branch close to the bladder. Micturition contractions were triggered at different bladder volumes by a brief train of electrical stimulation of bladder afferents while monitoring post-stimulus efferent activity and reflex bladder contractions. The degree of obstruction was assessed by bladder wet weight at the end of the experiment. Bladder weight, micturition threshold volume, anatomical bladder capacity and peak contraction force were significantly increased in obstructed rats. In sham operated controls a triggered micturition reflex was sustained by afferent feedback from the bladder until the bladder was empty. In contrast, reflex discharges failed with substantial volume remaining in the bladder in obstructed rats. The minimal micturition reflex volume correlated positively with bladder weight, micturition threshold volume and maximal bladder capacity (r ≥0.74). In rats with partial bladder outlet obstruction the micturition reflex failed before the bladder was empty due to a decreased afferent drive from bladder mechanoreceptors. Similar changes may contribute to post-void residual urine in humans with bladder outlet obstruction.

International children's continence society's recommendations for therapeutic intervention in congenital neuropathic bladder and bowel dysfunction in children

We present a consensus view of members of the International Children's Continence Society on the therapeutic intervention in congenital neuropatic bladder and bowel dysfunction in children. Discussions were held by a group of pediatric urologists and gastroenterologists appointed by the board. The following draft review document was open to all the ICCS members via the ICCS web site. Feedback was considered by the core authors and by agreement, amendments were made as necessary. The final document is not a systematic literature review. It includes relevant research when available as well as expert opinion on the current understanding of therapeutic intervention in congenital neuropatic bladder and bowel dysfunction in children. Guidelines on pharmalogical and surgical intervention are presented. First the multiple modalities for intervention that do not involve surgical reconstruction are summarized concerning pharmacological agents, medical devices, and neuromodulation. The non-surgical intervention is promoted before undertaking major surgery. Indicators for non-surgical treatments depend on issues related to intravesical pressure, upper urinary tract status, prevalence of urinary tract infections, and the degree of incontinence. The optimal age for treatment of incontinence is also addressed. This is followed by a survey of specific treatments such as anticholinergics, botulinum-A toxin, antibiotics, and catheters. Neuromodulation of the bladder via intravesical electrical stimulation, sacral nerve stimulation, transcutaneous stimulation, and biofeedback is scrutinized. Then follows surgical intervention, which should be tailored to each individual, based on careful consideration of urodynamic findings, medical history, age, and presence of other disability. Treatments mentioned are: urethral dilation, vesicostomy, bladder, augmentation, fascial sling, artificial urinary sphincters, and bladder neck reconstruction and are summarized with regards to success rates and complications. Finally, the treatment on neuropathic bowel dysfunction with rectal suppositories irrigation and transrectal stimulation are scrutinized.

Evaluating the use of different waveforms for intravesical electrical stimulation: A study in the rat

For decades, monophasic square wave pulses have been used for intravesical electrical stimulation (IVES) in diagnosis and treatment of lower urinary tract dysfunction. The use of other waveforms, more preferred by patients or more effective for neural stimulation, has hardly been studied before. This study compares the effect of several waveforms and derived parameters in IVES. IVES, performed in eight female Sprague-Dawley rats, was given for 300 sec with constant frequency (10 Hz) and current amplitude (6 mA) with unipolar square, biphasic square, asymmetric biphasic square, double square, unipolar exponential rise, biphasic exponential rise, and double-exponential rise wavepulses with different pulse durations (2 × 5 msec, 20 msec, or 2 × 20 msec). Bladder pressure was recorded. Average current and average power were calculated. Stimulations with the different waveforms resulted in the same maximal pressure rise (all P>0.1). The average charge was zero for biphasic waveforms. For exponential rise pulse waveforms the total injected charge was lower than that for the monophasic square pulse waveform. The average power was the highest for biphasic waveforms and the lowest for monophasic double-exponential rise pulses waveform. Charge-balanced waveforms, which are more preferred by patients, are equally effective in evoking IVES-induced detrusor contraction as monophasic square pulse waveforms. Thus, it can be beneficial in clinical practice to replace the monophasic square pulse waveform for IVES by charge-balanced waveforms. Furthermore, the stimulation power and thus the requested energy can be reduced by changing the waveform. This can be important for electrical stimulation using implanted batteries.

Exploring the mechanisms of intravesical electrical stimulation in the in vitro rat whole bladder after treatment with atropine, α,β-methylATP and tetrodotoxin

In a previous study, we showed that the working mechanism of intravesical electrical stimulation (IVES) is probably mainly nerve mediated. But even after bladder decentralization, IVES can induce detrusor contraction. This study explores the effect of IVES in decentralized bladders and the importance of receptors in the bladder wall for a response on IVES. IVES (10 Hz square wave pulses, 20 msec pulse duration, 6 mA) was used in the bladder of 16 female Sprague-Dawley rats. After repeating IVES after consecutive bilateral bladder nerves section (L6-roots, pelvic nerves, and major pelvic ganglion (MPG)), the bladders were mounted in a tissue bath. IVES was performed in the control (n=16), after administration of tetrodotoxin (TTX) (n=6), after atropine and atropine with α,β-methylATP (n=6), and after α,β-methylATP and α,β-methylATP with atropine (n=4). The IVES-induced pressure rise (ΔP) was recorded. Maximum ΔP (maxΔP) after transection of the MPG was significantly lower than after pelvic nerves transection. Treatment with TTX and with α,β-methylATP plus atropine abolished ΔP. Atropine alone gave an insignificant decrease of maxΔP. Treatment with α,β-methylATP alone reduced maxΔP significantly. IVES can evoke contractions in a decentralized bladder. IVES-induced contractions are not a result of direct muscle stimulation, but are nerve mediated, involving intramural innervation and several parts of the bladder innervation. IVES-evoked contraction can be divided in a, contraction duration determining, cholinergic part and a, contraction strength determining, purinergic part. The peripheral innervation could play a role in IVES treatment in patients with interrupted central reflex pathway.

The effect of intravesical electrical stimulation on bladder function and synaptic neurotransmission in the rat spinal cord after spinal cord injury

To investigate the effects of intravesical electrical stimulation (IVES) on bladder function and synaptic neurotransmission in the lumbosacral spinal cord in the spinalized rat, as the clinical benefits of IVES in patients with increased residual urine or reduced bladder capacity have been reported but studies on the mechanism of IVES have mainly focused on bladder A delta afferents in central nervous system-intact rats. In all, 30 female Sprague-Dawley rats were divided equally into three groups: normal control rats, sham-stimulated spinalized rats and IVES-treated spinalized rats. IVES was started 5 weeks after spinal cord injury (SCI) and was performed 20 min a day for 5 consecutive days. At 7 days after IVES, conscious filling cystometry was performed. Sections from the L6 and S1 spinal cord segments were examined for n-methyl-d-aspartic acid receptor 1 (NMDAR1) subunit and gamma-aminobutyric acid (GABA) immunoactivity. In IVES-treated spinalized rats, the number and maximal pressure of nonvoiding detrusor contractions were significantly less than in sham-stimulated spinalized rats. The mean maximal voiding pressure was also lower in IVES-treated than in sham-stimulated spinalized rats. IVES significantly reduced the interval between voiding contractions compared with the untreated spinalized rats. There was an overall increase in NMDAR1 immunoactivity after SCI, which was significantly lower in IVES-treated spinalized rats. Immunoactivity of GABA after SCI was significantly lower than in the control group and was significantly higher in IVES-treated spinalized rats. Our results suggest that IVES might affect voiding contractions in addition to inhibiting C-fibre activity and that IVES seems to have a more complex effect on the bladder control pathway. For synaptic neurotransmission in the spinal cord, IVES could possibly shift the balance between excitation and inhibition towards inhibition.

Can the use of different parameters and waveforms improve the results of intravesical electrical stimulation: A pilot study in the rat

Intravesical electrical stimulation (IVES) with square wave pulses, low frequencies and short pulse durations has been used for decades in diagnosis and treatment of lower urinary tract dysfunction. The results are not always satisfying. Several parameters have been studied before but not the use of other waveforms and the effect of electrical charge. This study compares the effect of changing waveforms, frequencies, pulse durations, amplitudes and derived parameters in IVES. IVES, performed in seven female Sprague-Dawley rats, was given for 10 sec with constant current unipolar square or sawtooth pulses with different pulse durations (10, 20, or 100 msec), frequencies (5, 20, or 10 Hz) and amplitudes (2, 4, 6, and 8mA). Bladder pressure was recorded. Electrical charge and power were calculated. Stimulation with the same frequency, same pulse duration and same amplitude showed significantly higher maximal pressure rises (max DeltaP) for square wave (all P < 0.05). Stimulation with the same frequency, same pulse duration and same electrical charge, gave no different max DeltaP for both waveforms (all P > 0.05). The charge and power could be reduced without changing max DeltaP, by lowering frequencies and/or shortening pulse durations. Sawtooth pulses are equally effective as square pulses for inducing detrusor contraction during IVES with the same electric charge. Frequency and pulse duration had, in this study, a minor influence on the efficacy of IVES. Lower frequency and/or shorter pulse duration results in lower charge and power without changing stimulation efficacy. This finding can be important for the battery life of implanted stimulators and for patient's comfort.