Inhibitory Effect and Possible Mechanism of Intraurethral Stimulation on Overactive Bladder in Female Rats

Yu Tian,Limin Liao,Jean Jacques Wyndaele 대한배뇨장애요실금학회 2015 International Neurourology Journal Vol.19 No.3

Purpose: To investigate the inhibitory effect and possible mechanism of intraurethral stimulation on overactive bladder (OAB) induced by acetic acid irritation. Methods: Cystometry was performed in 13 urethane-anesthetized female rats. Intravesical infusion of 0.5% acetic acid was used to irritate the bladder and induce OAB. Multiple cystometrograms were performed with mirabegron, continuous stimulation, mirabegron plus continuous stimulation, and β3-adrenoceptor antagonist plus continuous stimulation to determine the mechanism underlying the inhibitory effect by intraurethral stimulation. Results: Infusion of acetic acid significantly decreased bladder capacity. Intraurethral stimulation at 2.5 Hz plus mirabegron significantly increased bladder capacity and decreased the nonvoiding contraction count. The changes were strongly inhibited after the β3-adrenoceptor antagonist was administered. Conclusions: Activation of urethral afferent nerves can reverse OAB, which activates C-fiber afferent nerves. This animal study indicates that intraurethral stimulation may interfere with OAB through hypogastric nerve activation and pudendal nerve neuromodulation.

Typical Value Ranges and Typical Signal Patterns in the Initial Cough in Patients With Neurogenic Bladder: Quality Control in Urodynamic Studies

Tianji Lu,Limin Liao 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.3

Purpose: The goal of this study was to establish typical value ranges (TVRs) and to analyze typical signal patterns (TSPs) of the initial cough (cough before bladder filling) for quality control in urodynamic studies. Methods: A total of 539 urodynamic traces from patients with neurogenic bladder obtained over the course of a year were retrospectively reviewed. The TVRs for cough amplitude in measurements of the intravesical pressure (Pves), abdominal pressure (Pabd), and detrusor pressure (Pdet) during the initial cough were established. We used the 95% range as a reference range for all parameters. Cough spikes in Pdet were described and classified, and the reasons for different patterns of cough spikes were established. The quality of all the cystometry traces was checked, and we also present remedial actions for inappropriate cough spikes. Results: The cough amplitudes in the measurements of Pves and Pabd were similar, with 95% of measurements falling within the following ranges: 4–62 cm H2O and 3–70 cm H2O, respectively, in supine position and 9–95 cm H2O and 8–98 cm H2O, respectively, in sitting position. For Pdet, the cough amplitude ranged from −38 to 25 cm H2O in supine position and from −44 to 41 cm H2O in sitting position. The cough spikes for Pdet were classified as follows: type I, Pdet pressure exhibited a minimal change (<5 cm H2O) during the cough; type II, a monophasic spike (>5 cm H2O) was observed for Pdet; and type III, biphasic spikes were observed for Pdet. Type I coughs were found to have more high-quality traces (P<0.01). Conclusions: TVRs for the initial cough test among neurogenic patients were established in order to provide guidelines for quantitative quality control. The TSPs for the initial cough signal were described, and the presence of a high-quality cough signal may be recommended as a component of quality control in urodynamic measurements.

Nano-BTA: A New Strategy for Intravesical Delivery of Botulinum Toxin A

Qinggang Liu,Limin Liao 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.2

Botulinum neurotoxin subtype A (BoNT-A) has been part of the urology treatment arsenal since it was first used in the treatment of detrusor-sphincter dyssynergia more than 30 years ago. BoNT-A has been recommended as an effective treatment for neurogenic detrusor overactivity and overactive bladder. However, direct intradetrusor injection of BoNT-A using cystoscopy after anesthesia may cause hematuria, pain, and infection; these adverse events have motivated urologists to find less invasive and more convenient ways to administer BoNT-A. The development of nanotechnology has led to the advancement of intravesical drug delivery. Using versatile nanocarriers to transport BoNT-A across the impermeable urothelium is a promising therapeutic option. In this review, we discuss the effectiveness and feasibility of liposomes, thermosensitive polymeric hydrogels, and hyaluronan-phosphatidylethanolamine as carriers of BoNT-A for intravesical instillation. To date, these carriers have not reached a similar efficacy as intradetrusor injections in long-term observations. Hopefully, researchers will make a breakthrough with new nanomaterials to develop clinical applications in the future.

Effects of Acute Sacral Neuromodulation at Different Pulse Widths on Bladder Overactivity in Pigs

Huiling Cong,Limin Liao,Yiming Wang,Lingna Zhao,Zhaoxia Wang,Guang Fu,Guoqing Chen 대한배뇨장애요실금학회 2019 International Neurourology Journal Vol.23 No.2

Purpose: Sacral nerve stimulation has been used to treat overactive bladder. This study evaluated the effects of stimulation using different pulse widths on the inhibition of bladder overactivity by sacral nerve stimulation (SNM) in pigs. Methods: Implant-driven stimulators were used to stimulate the S3 spinal nerve in 7 pigs. Cystometry was performed by infusing normal saline (NS) or acetic acid (AA). SNM at pulse widths of 64 μsec to 624 μsec was conducted at the intensity threshold at which observable perianal and/or tail movement was induced. Multiple cystometrograms were performed to determine the effects of different pulse widths on the micturition reflex. Results: AA-induced bladder overactivity reduced the bladder capacity to 46.9%±7.1% of the NS control level (P<0.05). During AA infusion, SNM at 64 μsec, 204 μsec, and 624 μsec increased the bladder capacity to 126.1%±6.9%, 129.5%±7.3%, and 140.1%±7.6% of the AA control level (P<0.05). No significant differences were found among the results obtained using pulse widths of 64 μsec, 204 μsec, and 624 μsec (P>0.05). The actual intensity threshold varied from 0.7 to 8 V. The mean intensity threshold (T visual) for pulse widths of 64 μs, 204 μs, and 624 μs were 5.64±0.76 V, 3.11±0.48 V, and 2.52±0.49 V. T visual for pulse widths of 64 μsec was larger than the other two T visual for pulse widths of 204 μsec and 624 μsec (P<0.05). No significant differences were found among the T visual for pulse widths of 204 μsec and 624 μsec (P>0.05). Conclusions: This study indicated that different pulse widths could play a role in inhibiting bladder overactivity. It is not yet certain which pulse widths increased bladder capacity compared with AA levels, to minimize energy consumption and maintain patient comfort during stimulation, 204 μsec may be an appropriate pulse width for SNM.

Effects of Acute Sacral Neuromodulation at Different Frequencies on Bladder Overactivity in Pigs

Xing Li,Limin Liao,Guoqing Chen,Zhaoxia Wang,Han Deng 대한배뇨장애요실금학회 2017 International Neurourology Journal Vol.21 No.2

Purpose: We investigated the effects of different stimulation frequencies on the inhibition of bladder overactivity by sacral neuromodulation (SNM) in pigs. Methods: Implant-driven stimulators were used to stimulate the S3 spinal nerve in 13 pigs. Cystometry was performed by infusing normal saline (NS) or acetic acid (AA). SNM (pulse width, 210 μsec) at frequencies ranging from 5 to 50 Hz was conducted at the intensity threshold at which observable perianal and/or tail movement was induced. Multiple cystometrograms were performed to determine the effects of different frequencies on the micturition reflex. Results: AA-induced bladder overactivity significantly reduced the bladder capacity (BC) to 34.4%±4.7% of the NS control level (354.4±35.9 mL) (P<0.05). During AA infusion, SNM at 5 Hz did not significantly change the BC (48.1%±6.9% of the NS control level) (P>0.05), but SNM at 15, 30, and 50 Hz significantly increased the BC to 54.5%±7.1%, 55.2%±6.5%, and 57.2%±6.1% of the NS control level (P<0.05), respectively. No significant differences were found among the results obtained using frequencies of 15, 30, and 50 Hz (P>0.05). Conclusions: This study demonstrated that 15 Hz was an appropriate frequency for SNM and that frequencies higher than 15 Hz did not lead to better surgical outcomes.

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

Han Deng,Limin Liao,Xing Li,Qinggang Liu,Xuesheng Wang,Zhonghan Zhou 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.4

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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

The Comparative Effectiveness of Botulinum Toxin-A Injection Therapy Versus Augmentation Uretero-Enterocystoplasty for the Treatment of Lower Urinary Tract Dysfunction

Xuesheng Wang,Zhonghan Zhou,Limin Liao 대한배뇨장애요실금학회 2023 International Neurourology Journal Vol.27 No.1

urpose: We investigated the effectiveness of intravesical botulinum toxin-A (BTX-A) injection therapy in patients with lower urinary tract dysfunction (LUTD) and upper urinary tract (UUT) deterioration and evaluated whether BTX-A injection therapy could substitute for augmentation uretero-enterocystoplasty (AUEC). Methods: Data from a prospective, single-center cohort from 2017–2021 were analyzed. Patients were divided into 2 treatment groups: AUEC and BTX-A (i.e., patients who declined AUEC). Bladder and UUT functions were assessed by comparing clinical information, urodynamic data, laboratory results, and imaging records. Results: In total, 121 patients were enrolled (BTX-A group: 41 patients; AUEC group: 80 patients). The BTX-A group showed a reduced maximum detrusor pressure and increases in the maximum bladder volume and bladder compliance (P<0.05). However, in follow-up evaluations, significantly smaller improvements (all P<0.05) in urodynamic parameters were found in the BTX-A group than in the AUEC group. Notably, there was no significant improvement in vesicoureteral reflux (VUR; P=0.66) or upper urinary tract dilatation (UUTD; P=0.75) in the BTX-A group, and no statistically significant difference in serum creatinine (Scr) levels or the estimated glomerular filtration rate (eGFR) was observed in the follow-up evaluations (all P>0.05). Both VUR and UUTD improved significantly in the AUEC group, and the Scr and eGFR levels significantly improved after AUEC relative to baseline levels (P<0.05). The reduction in the Scr level was significantly lower in the BTX-A group than in the AUEC group during 0–15 months of follow-up (Scr reduction differences, -1.36; P<0.01). Conclusions: Although BTX-A injection therapy was effective for improving bladder function, BTX-A injections did not alleviate UUT deterioration in this study, particularly in patients with advanced-stage LUTD. Conversely, AUEC for LUTD has a well-established role in improving UUT function. Hence, BTX-A injection therapy should not replace AUEC to ameliorate UUT impairment and protect UUT function.

Risk Factors Predicting Upper Urinary Tract Damage in Patients With Myelodysplasia: Data Analysis of 637 Cases From A Single Center

Han Deng,Zhaoxia Wang,Limin Liao,Juan Wu,Yue Wang 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.S1

Purpose: To determine the risk factors predicting upper urinary tract (UUT) damage using a grading system for upper urinary tract dilation (UUTD) and a descriptive system for all urinary tract dysfunction (AUTD) in patients with myelodysplasia. Methods: Six hundred thirty-seven patients with myelodysplasia were evaluated at our center from January 2008 to November 2019. Clinical data, ultrasonography, magnetic resonance urography, and video-urodynamics (VUDS) parameters were collected. Univariate and multivariate analyses were used to determine the risk factors predicting UUT damage. Results: Three hundred eighty-three males and 254 females were included. The average course of lower urinary tract symptoms (LUTS) was 14.08±7.07 years (range, 3–31 years). The urodynamic diagnoses of all patients were as follows: detrusor overactivity, 26.8%; detrusor underactivity, 6.44%; and acontractile detrusor, 66.72%. UUT damage was determined in 66.56% of the patients. Of the patients, 28.73 % had vesicoureteral reflux (VUR) during filling (bilateral, n=50; unilateral, n=133) on fluoroscopy during VUDS testing. Two hundred thirty-four patients had UUTD (bilateral, n=203; unilateral, n=31). The occurrence of hydronephrosis based on ultrasonography was closely related to ipsilateral VUR (P<0.05). Absent of bladder sensation, long-term course of LUTS, decreased maximum cystometric capacity (MCC) and bladder compliance (BC), and increased postvoid residual urine (PVR) were shown to be independent risk factors in logistic regression analysis. Conclusions: This retrospective study using UUTD and AUTD systems indicated that patients with myelodysplasia have a high incidence of UUT damage. Absence of bladder sensation, long-term course of LUTS, decreased MCC and BC, and increased PVR were independent risk factors predicting UUT damage.

The Video-Urodynamic and Electrophysiological Characteristics in Patients With Traumatic Spinal Cord Injury

Zhaoxia Wang,Han Deng,Xing Li,Limin Liao 대한배뇨장애요실금학회 2021 International Neurourology Journal Vol.25 No.4

Purpose: To investigate the video-urodynamic and pelvic floor electrophysiological characteristics in patients with traumatic spinal cord injury (SCI). Methods: This retrospective reviewed the clinical records, urodynamic and pelvic floor electrophysiological data of 647 patients with traumatic SCI and out of spinal shock. Patients were classified based on American Spinal Injury Association (ASIA) Impairment Scale and urodynamic findings. Results: Of the 647 patients, detrusor overactivity (DO) with or without detrusor sphincter dyssynergia (DSD) was found in 79.5%, 61%, 35.2%, 35%, and 19.2% of patients with cervical, thoracic (T1–9), thoracic (T10–12), lumbar, and conical cauda injury, respectively. Other patients manifested detrusor areflexia (DA). Patients with DO and/or DSD had a longer duration of SCI at each injury level than patients with DA. In suprasacral injury patients with DA, 63.0% (58 of 92) had a normal bulbocavernosus reflex (BCR) response. Compared with patients without bladder sensation (BS), bladder capacity during urine leakage was far higher in those with BS. The manifestation of BCR and somatosensory-evoked potential (SEP) was associated with the level of injury. Conclusions: This study showed a significant correlation between the level of SCI and video-urodynamic findings, but clinical examination cannot by predict bladder function; urodynamic testing is also necessary. In addition, the role of BCR and SEP for guiding bladder management is limited. Moreover, BS is important for urinary control in patients with traumatic SCI.

Frequency-Dependent Effects on Bladder Reflex by Saphenous Nerve Stimulation and a Possible Action Mechanism of Tibial Nerve Stimulation in Cats

Xing Li,Xiaoping Wan,Zhaoxia Wang,Yanan Liang,Zhuo Jia,Xu Zhang,Limin Liao 대한배뇨장애요실금학회 2021 International Neurourology Journal Vol.25 No.2

Purpose: The present study determined the effects of saphenous nerve stimulation (SNS) at different stimulation frequencies on bladder reflex and explored a possible action mechanism of tibial nerve stimulation (TNS) on bladder activity in cats. Methods: Two bipolar nerve cuff electrodes were implanted on the saphenous nerve and the contralateral tibial nerve in 13 cats, respectively. Multiple cystometrograms were obtained to determine the effects of single SNS at different frequencies and that of combined SNS and TNS on the micturition reflex by infusing normal saline. Results: SNS at 1 Hz significantly reduced the bladder capacity (BC) to 59.8%±7.7% and 59.3%±5.8% of the control level at the intensity threshold (T) and 2T, respectively (P<0.05), while that at 20 Hz significantly increased the BC to 130.6%±4.2% of the control level at 6T (P<0.05). The TNS and SNS at 20 Hz did not significantly change the BCs at 1T (P>0.05), while combined stimulation at 1T significantly increased the BC to 122.7%±1.9% of the control level and induced an inhibitory effect which was similar to that TNS at 2T. Conclusions: The current study revealed that SNS reduced and increased BC depending on different stimulation frequencies. The combined SNS and TNS maximized the clinical efficacy at a low intensity. Also, SNS may be a potential therapeutic mechanism of TNS.