Leak Point Pressure Measurement Research Articles

Microenergy acoustic pulse therapy restores urethral wall integrity and continence in a rat model of female stress incontinence.

To determine the outcomes and mechanisms of microenergy acoustic pulse (MAP) therapy in an irreversible rat model of female stress urinary incontinence. Twenty-four female Sprague-Dawley rats were randomly assigned into four groups: sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + β-aminopropionitrile (BAPN), and VBDO + β-aminopropionitrile treated with MAP (MAP). MAP therapy was administered twice per week for 4 weeks. After a 1-week washout period, all 24 rats were evaluated with functional and histological studies. The urethral vascular plexus was examined by immunofluorescence staining with antibodies against collagen IV and von Willebrand factor (vWF). The urethral smooth muscle stem/progenitor cells (uSMPCs) were isolated and functionally studied in vivo and in vitro. Functional study with leak point pressure (LPP) measurement showed that the MAP group had significantly higher LPPs compared to VBDO and BAPN groups. MAP ameliorated the decline in urethral wall thickness and increased the amount of extracellular matrix within the urethral wall, especially in the urethral and vaginal elastic fibers. MAP also improved the disruption of the urethral vascular plexus in the treated animals. In addition, MAP enhanced the regeneration of urethral and vaginal smooth muscle, and uSMPCs could be induced by MAP to differentiate into smooth muscle and neuron-like cells in vitro. MAP appears to restore urethral wall integrity by increasing muscle content in the urethra and the vagina and by improving the urethral vascular plexus and the extracellular matrix.

Validation of a new rat model of urethral sphincter injury and leak point pressure measurements

Aims In vivo experiments were performed to establish and validate a rat model of urethral sphincter injury and to develop a method for leak point pressure (LPP) measurements performed repeatedly in the same animal. Methods Twenty-four Sprague-Dawley female rats underwent bladder and epidural catheter implantation. Five days later, cystometry was performed using continuous infusion. Anesthesia with isoflurane, ketamine-xylazine (KX) or fentanyl-fluanisone-midazolam (FFM) was used. After three micturition cycles, intrathecal bupivacaine was administered leading to the suppression of reflex bladder contractions. LPP measurements were performed using vertical tilt. After the initial LPP measurement, animals underwent partial resection of the striated urethral sphincter. The effect was evaluated 6 weeks after surgery, by repeating the LPP measurement in the same animal. Results Ten out of 19 animals showed full micturition cycles under isoflurane, and all 9 animals under KX anesthesia. No significant difference in micturition pressures (Mean ± SEM; 30.1 ± 2.3 vs. 26.8 ± 1.6 mmHg) and LPP (31.0 ± 2.4 vs. 28.0 ± 0.9 mmHg) was observed between isoflurane and KX groups, respectively. Reflex micturition was suppressed with FFM. Bupivacaine led to overflow incontinence in all cases. Sphincter injury caused fibrotic changes and a significant increase in LPP (26.4 ± 2.3 before vs. 46.9 ± 4.6 mmHg after injury, p < 0.05). Conclusions KX anesthesia preserves bladder contractions. Intrathecal bupivacaine eliminates reflex micturition, allowing for repeated LPP measurements in the same animal. Resection of striated sphincter resulted in increased LPP 6 weeks post injury. The site of urethral sphincter resection healed with fibrosis.

Urodynamic Studies for the Diagnosis of Lower Urinary Tract Symptoms: Experience in BSMMU

Objectives: The aim of urodynamic testing is to obtain objective information regarding urinary bladder storage and voiding function. This investigation provides information of the underlying causes depending on the individual situation and findings. Materials and Methods: This Retrospective study of the UDS was conducted at Urology department of Bangabandhu Sheikh Mujib Medical University, Dhaka from January 2012 to April 2017. A total of 403 cases of urodynamic studies done. Patient age range was 10-85 years. Female Patient was only 41 and post operative cases was only six. Bladder dairy, Ultrasonography of Kidney, ureter, bladder with maximum cystometric capacity (MCC)and post void residue (PVR), Urine culture were done for most of the patient. Patient with indwelling catheter was remove and clean intermittent catheterization was demonstrated. There was no patient with pace maker or valve replacement. We didn’t use routine prophylactic antibiotics, Patients was advice to contact to UDS room physically or over telephone if they feel fever, retention, and other complications. Urodynamic tests include uroflowmetry, postvoid residual measurement, cystometric test, leak point pressure measurement, pressure flow study, and few cases with electromyography. Results: Among them most cases are equivocal and obstructive cases are ranked second about 68 cases (16.87 These were Benign Prostatic Hyperplasia (BPH), stricture urethra, atonic bladder, and dysfunctional voiding. Only five patients had urinary tract infections (1.2%) with rise of temperature but only two had cultural positive and treated with sensitive antibiotics. Organism were streptococcus aureus and pseudomonus. One female and one male patient develop retention and relived by continuous catheterisation and after 7 days removed catheter. Conclusions: Urodynamics could help most diagnosis of LUTSs in most of the cases. We are not yet in using video urodynamics instead urethrocystoscopy may help in assessing the urethra and bladder neck. Bangladesh Journal of Urology, Vol. 21, No. 1, January 2018 p.8-13

Association of intrinsic sphincter deficiency with urine flow acceleration measurement.

Intrinsic sphincter deficiency (ISD) is associated with an inability to maintain mucosal coaptation either at rest or in the presence of stress resulting from damage to muscles or nerves that maintain tonus. The purpose of our trial was to determine the role of urodynamic measurements of flow such as maximum flow rate, flow time, and acceleration speed of flow to assess the urethral resistance on prediction of stress incontinence and ISD. Our study was based on a retrospective analysis of urodynamic records of female patients performed for urinary incontinence. Mean flow rate, maximum flow rate, detrusor pressure at maximum flow, vesical pressure at maximum flow, maximum detrusor pressure, and flow rate at maximum detrusor pressure measurements were extracted from the voiding phase of urodynamic charts. The slope of the maximum flow was used to calculate acceleration of flow (Qacc). The urodynamic records of 142 women were reviewed and Qacc was measured. The mean age of the ISD group was 53.3 ± 12.5 (24-78) and of the non-ISD group 53.7 ± 12.5 (35-74). The mean Qacc (30.3 ± 16.1° [mL/s2 ]) in the ISD group was significantly higher than in the non-ISD group (21.6 ±9.6° [mL/s2 ]). Urodynamic bladder capacity of the non-ISD group (432.3 ± 90.4 mL) was higher than the ISD group (389.2 ± 109) (P = .01). The Valsalva leak point pressure and maximum urethral closure pressure measurements in assessing urethral function are not useful for predicting incontinence surgery failure. We demonstrated that Qacc is higher in ISD stress incontinent women than stress incontinent women. Qacc may demonstrate urethral resistance and tonus in a more reliable manner.

Therapeutic new targets for stress urinary incontinence in the central nervous system

Stress urinary incontinence (SUI) is a common and bothersome problem among middle-aged women. However, there are few useful drugs for SUI. Urethral hypermobility and intrinsic sphincter deficiency are two main causes of SUI. Various animal models of SUI, such as vaginal distention, pudendal nerve injury, or ovariectomy, have been developed to study the pathophysiology of SUI. In addition, we have previously reported that cerebral infarction rats also induce SUI. Leak point pressure measurements are the most commonly used methods to evaluate the urethral dysfunction in SUI animal models. Originally, we have developed microtransducer-tipped catheter measurements of urethral activity during sneezing. Previous or our basic research has clarified potential strategies for pharmacotherapy of SUI in the central nervous system. Therapeutic targets include adrenergic and serotonergic (5-HT) receptors in the spinal cord, which stimulate pudendal nerve innervating the external urethral sphincter and/or sympathetic nerve innervating urethral smooth muscle. Activation of α1-adrenoceptors, 5-HT2C, or 5-HT7 receptors enhances the reflex at the spinal cord level whereas pre- or postsynaptic α2-adrenoceptors and/or 5-HT1A receptors inhibit the reflex. We have recently reported that stimulation of the spinal μ-opioid receptors by tramadol also enhances the reflex. Thus, we review the recent advances in basic SUI research and potential targets for pharmacotherapy of SUI in the central nervous system.

Influence of the urethral pressure transducer in measuring Valsalva leak point pressure in women undergoing multichannel urodynamic testing.

To determine if the air-charged urethral sensor balloon currently used in urodynamic testing (UDS) significantly impacts Valsalva leak point pressure (VLPP) measurements. This is a prospective cohort study of women undergoing UDS at an academic institution. VLPPs were obtained at 150 mL and urodynamic capacity with and without the urethral pressure sensor in the urethra. VLPP measurements were analyzed using a Wilcoxon signed-rank test. Median and interquartile range are presented. Sixty-three patients were enrolled in the study, 53 were included in the primary analysis. The mean age of the subjects was 56.2 ± 12.1 years. Nine patients (16%) solely leaked when the balloon was not present in the urethra either with cough or during VLPP measurement. At both 150 mL and urodynamic capacity, when VLPP testing was performed, there was a significant difference (cmH2 O) between the control and intervention values, (76.2 [55.0, 97.0] vs 68.8 [46.3, 93.3], P = .0012; 79.3 [53, 96.5] vs 72.5 [50.8, 92.3], P = .04). There was also a statistically significant difference between the control and intervention values for the lowest leak value at 150 mL and capacity (70.5 [51, 94.5] vs 60.0 [40, 88] P = .002; 73.5 [49.5, 91.5] vs 61 [45, 88], P = .017). The higher VLPPs obtained with the urethral balloon in place indicate that the balloon may be the cause of falsely elevated VLPPs during urodynamic testing. Additionally, the balloon may mask a diagnosis of stress urinary incontinence in some patients.

The effects of microenergy acoustic pulses on an animal model of obesity-associated stress urinary incontinence. Part 1: Functional and histologic studies.

Obesity is a strong independent risk factor for urinary incontinence. Effective therapeutic approaches for obesity-associated stress urinary incontinence (OA-SUI) are lacking as the mechanisms remain unclear. The aim of our study is to explore the impacts of microenergy acoustic pulse (MAP) therapy on urethral and pelvic floor muscle structure and function in female lean and fatty rats. A total 24 Zucker fatty (ZF) and 24 Zucker lean (ZL) female 24-week-old rats were grouped into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. For MAP treatment, 500 pulses were delivered at an energy level of 0.033 mJ/mm 2 and a frequency of 3 Hz and were applied twice a week for 4 weeks. After a 1-week washout, all rats underwent conscious cystometry and leak-point pressure (LPP) measurements followed by ex vivo organ-bath assay and histological study. ZF rats had lower LPP as compared to ZL rats, and MAP treatment significantly improved LPP in ZF rats (P < .05). Impaired muscle contractile activity (MCA) in organ-bath study was noted in ZF rats. MAP treatment significantly increased MCA in ZF rats (P < .05) and also increased the thickness of the striated muscle layer and the number of neuromuscular junctions (NMJs). In situ, MAP activated muscle satellite cells significantly (P < .05). Obesity impairs the function of both the urethral sphincter and the pelvic floor and leads to atrophy and distortion of the striated muscle in obese female rats. These issues contribute to OA-SUI. MAP improves continence by stimulating muscle regeneration and nerve innervation as well as by activating satellite cells.

An animal experimental study on pubourethral ligament restoration with platelet rich plasma for the treatment of stress urinary incontinence.

IntroductionMinimally invasive methods for injured ligament and tendon restoration have been developed and gained popularity in recent years. Injury and relaxation of the pubourethral ligament (PUL) can lead to stress urinary incontinence (SUI). The aim of this study was to investigate the impact of injecting platelet rich plasma (PRP) into the PUL following its surgical transection resulting in SUI, confirmed by leak point pressure (LPP) measurements pre- and post-intervention in an experimental animal model.Material and methodsTwenty female adult Sprague-Dawley rats were assigned in 2 groups: 1) treatment group with transection of the PUL and application of PRP at the time of transection and at one month follow-up and 2) a control group, with transection of the PUL only. Leak point pressures (LPPs) were measured prior to transection, immediately following the transection and at 1 and 2 months in both groups.ResultsThe median LPPs for the control group were: LPP – preT: 35.6 (29.8–44.8) cmH2O, LPP – postT: 14.6 (5.8–19.0) cmH2O, LPP – 1 month: 27.3 (19.2–33.8) cmH2O, LPP – 2 months: 29.0 (27.0–34.0) cmH2O, whereas for the PRP group were: LPP-preT: 40.5 (33.2–46.3) cmH2O, LPP – postT: 15.7 (3.0–24.0) cmH2O, LPP – 1month: 31.6 (24.8–37.4) cmH2O, LPP – 2 months: 36.8 (32.5–45.4) cmH2O. PRP injections on transected PULs significantly increased LPPs at one month follow-up [31.6 cmH2O vs. 27.3 cmH2O, p = .043]. This effect was confirmed at two months [36.8 cmH2O vs. 29.0 cmH2O, p <.001].ConclusionsInjection of PRP into transected PULs significantly improved LPPs at one and two months' follow-up. However, further experimental and clinical research is needed to evaluate the safety and efficacy of this treatment, in clinical practice.

Retrograde leak point pressure measurement improves outcomes of the Virtue male sling for postprostatectomy incontinence.

We aimed to compare the efficacy of two different sling tensioning approaches, and to report our experience, including safety and impact on quality of life (QoL) of the Virtue® male sling for the treatment of postprostatectomy incontinence (PPI). From our prospectively maintained database, we retrospectively identified all men treated with the Virtue male sling for PPI between March 2009 and February 2014 by two urologists in two institutions. Baseline demographic data and the sling tensioning method were abstracted from the database. Likewise, the Patient Global Impression of Improvement (PGI-I) scale, severity of incontinence, and clinical outcomes were also abstracted. 48 patients were treated with the Virtue quadratic male sling. Sling tensioning was done using cystoscopy in the first 18 patients (Group 1), while per-operative retrograde leak point pressure (RLPP) measurement was done in the last 30 patients (Group 2). The median (interquartile range [IQR]) followup from the day of surgery was 22 (15-41) months. At the last followup visit, 7 (39%) patients in Group 1 were cured or improved of their PPI, compared to 21 (70%) patients in Group 2 (p=0.03). The final median (IQR) RLPP in these patients was 41 (37-48) cm H2O. Transient pain was the most common adverse event, occurring in 23 (48%) of patients. Twenty-one (70%) patients in Group 2 were "much better" or "very much better" with their device, compared to 7 (39%) in Group 1 (p=0.0008). The Virtue male sling is a valuable treatment option for PPI. Per-operative RLPP measurement significantly improves cure and satisfaction rates.

Valsalva Leak Point Pressure Measurement in Women with Stress Urinary Incontinence: At what Bladder Volume?

Valsalva Leak Point Pressure Measurement in Women with Stress Urinary Incontinence: At what Bladder Volume?

Variables affecting maximum urethral closure pressure (MUCP) and abdominal leak point pressure (ALPP) measurements.

The relationship between pelvic floor muscles and measurements of urethral function is not well studied. It is not known whether adjusting for clinical, demographic and urodynamic parameters would improve the association between MUCP and ALPP. Our hypothesis was that pelvic floor muscle strength (PFMS) influences the relationship between MUCP and ALPP. This was a retrospective study of women who underwent a complex urodynamic study with evaluation of MUCP and ALPP using ICD-9 codes with documentation of PFMS. Urodynamic stress incontinence was confirmed in 478 patients, of whom 323 had MUCP recorded and 263 had both MUCP and ALPP recorded. Women with higher PFMS had a higher MUCP. In regression analysis ALPP at 150mL and MUCP were weakly associated (coefficient 0.43, 95% CI 0.08-0.78; p=0.02), whereas ALPP at capacity and MUCP were moderately associated (coefficient 0.60, 95% CI 0.25-0.95; p<0.001). This study showed that MUCP and ALPP at 150mL were weakly associated and that this improved to a moderate association for ALPP at capacity. MUCP increased with increasing PFMS among women with stress urinary incontinence and decreased with increasing age. There was no evidence that ALPP was associated with PFMS or age. The relationship between MUCP and ALPP was unchanged when accounting for covariates of PFMS (age, parity, BMI, prior procedure, urethral mobility, bladder capacity, stage of cystocele, or stage of uterine or apical prolapse).

MP65-01 STROMAL CELL DERIVED FACTOR-1 ACCELERATES RECOVERY OF CONTINENCE IN RAT MODEL OF VAGINAL DISTENSION INJURY

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II1 Apr 2016MP65-01 STROMAL CELL DERIVED FACTOR-1 ACCELERATES RECOVERY OF CONTINENCE IN RAT MODEL OF VAGINAL DISTENSION INJURY Ahmad Khalifa, Amr Mahran, Michael Kavran, Juliana Woda, Marc Penn, and Adonis Hijaz Ahmad KhalifaAhmad Khalifa More articles by this author , Amr MahranAmr Mahran More articles by this author , Michael KavranMichael Kavran More articles by this author , Juliana WodaJuliana Woda More articles by this author , Marc PennMarc Penn More articles by this author , and Adonis HijazAdonis Hijaz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1212AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Vaginal distension (VD) in rats results in a reproducible injury to urethral continence mechanism that is recoverable in 2 weeks. VD injury has been shown to cause ischemia. Stromal cell derived factor-1 (SDF-1), is a known chemokine involved in angiogenesis and chemo attraction of stem cells into injury area. Previously in animal and human studies, delivery of non-viral human SDF-1 plasmid (pSDF-1), which expresses SDF-1 for 2-3 weeks, has shown safety, increased vessel density and improved patient status in ischemic heart and vascular diseases. In this experiment we examined the efficacy of pSDF-1 injection on continence recovery after VD & correlated the changes with histological changes. METHODS A total of 72 Sprague Dawley rats underwent VD and were randomly divided into 2 groups. Group 1 (42 rats) underwent SDF-1 injection followed by Leak point pressure (LPP) measurement at 4, 7, and 14 days (14 rats per time point). Group 2 (30 rats) were sham injected (5% dextrose) after VD and LPP was measured at same time points (10 rats per time point). VD was done as described with inflation of a 10 French modified Foley catheter intravaginal for 4 hours to create injury. SDF-1 and dextrose were injected peri-uretherally immediately after VD. Following LPP measurement, urogenital tissues were harvested for histological examination. Slides were stained with H&E and Masson’s trichrome. Vascularity and collagen content was determined using Adobe Photoshop and Image J software. Data analysis was done by IBM SPSS v.22. RESULTS As expected, the LPP decreased at 4 days in both groups. SDF-1 group exhibited a significant increase in LPP at 7 days compared to the sham (22.3 cmH2O vs 13.62 3 cmH2O, P value <0.001 respectively). The improvement in LPP continued in both groups at day 14, with the statistical difference approaching significance (36.38 cmH2O vs 25.82 cmH2O respectively, p=0.067). Histological evaluation and image analysis revealed no gross differences in the smooth and skeletal muscle thickness of the mid-urethra with no statistically significant difference in the collagen content and vascular density in the urethra at all-time points. CONCLUSIONS pSDF-1 plasmid injection at the time of VD accelerated the recovery of continence in the rat model of simulated birth trauma. The mechanism of improved recovery is not evident from the gross histological evaluation. Further research is needed to explain the mechanism of early improvement, possible hypothesizes are stem cell attraction and decrease in cellular injury or death. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e864 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ahmad Khalifa More articles by this author Amr Mahran More articles by this author Michael Kavran More articles by this author Juliana Woda More articles by this author Marc Penn More articles by this author Adonis Hijaz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD35-05 HUMAN URINE-DERIVED STEM CELLS OR THEIR SECRETOME ALONE FACILITATE FUNCTIONAL RECOVERY IN A RAT MODEL OF STRESS URINARY INCONTINENCE

You have accessJournal of UrologyStem Cell Research1 Apr 2016PD35-05 HUMAN URINE-DERIVED STEM CELLS OR THEIR SECRETOME ALONE FACILITATE FUNCTIONAL RECOVERY IN A RAT MODEL OF STRESS URINARY INCONTINENCE Christine Tran, Abhi Tangada, Hualin Yi, Brian Balog, Yuanyuan Zhang, and Margot Damaser Christine TranChristine Tran More articles by this author , Abhi TangadaAbhi Tangada More articles by this author , Hualin YiHualin Yi More articles by this author , Brian BalogBrian Balog More articles by this author , Yuanyuan ZhangYuanyuan Zhang More articles by this author , and Margot DamaserMargot Damaser More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1077AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stem cell based therapy has emerged as a promising alternative to current female stress urinary incontinence (SUI) treatments. Human urine-derived stem cells (USCs) have no risk from biopsy but have not previously been investigated for SUI. One therapeutic mechanism of action of stem cells is secretion of bioactive growth factors or ″secretome″ that drives the regulation of many physiological processes via paracrine actions. We hypothesized that USCs or their secretome alone would promote functional recovery in a rodent model of female SUI. METHODS Thirty two-female Sprague-Dawley rats were randomized into 3 groups and underwent vaginal distension (VD) followed by intraperitoneal delivery of USCs (VD + USC), VD and saline, or sham VD and saline 1 hour after injury. To investigate if factors secreted by USCs facilitate functional recovery after VD, concentrated conditioned media (CCM) was generated by incubating confluent USCs in serum-free media for 24 hours. Cultured supernatant was then extracted, washed, and concentrated to form CCM. Concentrated media (CM) was created by concentrating serum-free media without the influence of cells. Thirty rats randomized into 3 groups underwent VD and intraperitoneal delivery of CCM (VD + CCM), VD and CM, or sham VD and CM 1 hour after injury. One week after injury, treatment efficacy was assessed by measurement of leak point pressure (LPP), and histological and immunocytochemical analysis of the urethra. RESULTS After 1 week, LPP significantly increased after VD in rats treated with USCs or CCM, compared to animals that received saline, and was similar to sham VD animals. On semiquantitative histological analysis, there was no significant difference between both the striated and smooth muscle components of the urethral sphincter of VD + USC and VD + CCM animals compared to sham VD animals; VD + saline and VD + CM animals, however, demonstrated significant muscle fiber attenuation and disorganization. Additionally, elastin fibers in VD + USC and VD + CCM animals were long, thickened, and mostly oriented compared to the short, thin, and disoriented fibers in VD + saline and VD + CM animals. No implanted USCs were found in the region of urethra. CONCLUSIONS Intraperitoneal injection of USCs and their secretions facilitate recovery from SUI in a rat model, likely via paracrine effects. Furthermore, elastogenesis may play a role in recovery of urethral function. USCs represent an attractive, alternate stem cell source with no biopsy risk to target the underlying pathophysiology in female SUI. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e845 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Christine Tran More articles by this author Abhi Tangada More articles by this author Hualin Yi More articles by this author Brian Balog More articles by this author Yuanyuan Zhang More articles by this author Margot Damaser More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP65-02 EFFECTS OF A SELECTIVE ANDROGEN RECEPTOR MODULATOR, GSK2849466A AND TESTOSTERONE ON STRESS URINARY INCONTINENCE IN OVARIECTOMIZED RATS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II1 Apr 2016MP65-02 EFFECTS OF A SELECTIVE ANDROGEN RECEPTOR MODULATOR, GSK2849466A AND TESTOSTERONE ON STRESS URINARY INCONTINENCE IN OVARIECTOMIZED RATS Takahiro Shimizu, Katsumi Kadekawa, Naoki Kawamorita, Philip Turnbull, Alan Russell, and Naoki Yoshimura Takahiro ShimizuTakahiro Shimizu More articles by this author , Katsumi KadekawaKatsumi Kadekawa More articles by this author , Naoki KawamoritaNaoki Kawamorita More articles by this author , Philip TurnbullPhilip Turnbull More articles by this author , Alan RussellAlan Russell More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1213AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stress urinary incontinence (SUI) is common in post-menopausal women, indicating that estrogen deficiency is one of the major causes of SUI that induces atrophic and degenerative changes in urethral and pelvic floor muscles. Selective androgen receptor modulators (SARMs) selectively stimulate anabolic pathway of the androgen receptor (AR) in muscle and bone while sparing the androgenic effects. In this study, we examined effects of a SARM (GSK2849466A, GSK) and dihydrotestosterone (DHT) on urethral continence function in a bilateral ovariectomy (OVX)-induced rat SUI model. METHODS Female nulliparous Sprague-Dawley rats with bilateral OVX were used. Rats were divided into 5 groups; sham operated (S), vehicle-treated OVX (O-V), GSK-treated OVX (0.005 or 0.03 mg/kg/day, po, O-L or O-H, respectively), and DHT-treated OVX (1 mg/kg/day, sc, O-D) groups. At 2 or 3 weeks after OVX, GSK (or vehicle) or DHT treatment was started. Six weeks after OVX, rats were subjected to the evaluation of sneeze-induced continence reflex and sneeze-induced leak point pressure (SLPP) measurements, followed by histological analyses of urethral tissues. RESULTS Urethral baseline pressure (UBP) and the amplitude of urethral responses during sneezing (AURS) were significantly reduced in O-V rats (n=11) by 46% and 38%, compared to S rats (n=8). Compared to the O-V, UBP was significantly increased in the O-L (n=6) and O-H (n=9) by 123% and 86%, and AURS was significantly increased in the O-H and O-D (n=10) by 106% and 60%. Fluid leakage was observed during sneezing in all O-V rats (n=8, SLPP=59.9 ± 9.5 cmH2O) whereas sham rats (n=8) did not leak. The leakage was also observed in O-L (7 of 9 rats, SLPP=67.4 ± 3.0 cmH2O), O-H (1 of 8 rats, SLPP=82.9 cmH2O) and O-D rats (3 of 8 rats, SLPP=73.2 ± 12.8 cmH2O). O-H rats showed hypertrophy/reversal of atrophy of striated (ST) and smooth (SM) muscles in urethral transverse sections, compared to O-V rats. CONCLUSIONS These results indicate that OVX significantly impairs urethral continence function after 6 weeks, and that GSK dose-dependently restores the reductions in UBP, AURS and SLPP accompanied with urethral muscle hypertrophy, leading to the prevention of SUI. Based on our previous studies, UBP and AURS predominantly reflect urethral SM and ST activity in rats. Considering that DHT restores the reduction in AURS without affecting reduced UBP and partially prevents SUI in OVX rats, SARMs could be more effective for the treatment of SUI by enhancing both SM and ST-mediated urethral function under stress conditions such as sneezing. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e864 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Takahiro Shimizu More articles by this author Katsumi Kadekawa More articles by this author Naoki Kawamorita More articles by this author Philip Turnbull More articles by this author Alan Russell More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

43: Variables affecting maximum urethral closure pressure (MUCP) and abdominal leak point pressure (ALPP) measurements

43: Variables affecting maximum urethral closure pressure (MUCP) and abdominal leak point pressure (ALPP) measurements

Leak point pressure at different bladder volumes in stress urinary incontinence in women: Comparison between Valsalva and cough-induced leak point pressure.

We compared Valsalva leak point pressure (VLPP) in urodynamically proven stress urinary incontinence (SUI) in women at different bladder volumes; examined the relationship between VLPP and cough-induced leak point pressure (CLPP) compared by incontinence severity; and evaluated the influence of bladder volume on each leak point pressure (LPP). Women with urodynamically proven SUI who underwent serial VLPP and CLPP measurement at bladder volumes of 150, 200, 250, and 300 mL were included in this study (n=228). LPP determination was repeated two times in each subject after finishing one series of LPP measurement. LPP at different bladder volumes was compared by subjective symptom severity of Stamey grade. Patients mean age was 51.3±7.6 years (range: 40-65 years). Stamey grade I, II, and III was assigned to 68 (29.8%), 102 (44.7%), and 58 (25.4%) patients, respectively. Mean CLPP was higher than VLPP (p=0.002) at every bladder volume. VLPP and CLPP were significantly decreased by the increase of bladder volume (p=0.001). The mean first positive LPPs were significantly lower at higher Stamey grade (p=0.004). LPP is more frequently induced by cough than by the Valsalva maneuver. VLPP and CLPP decreased significantly with bladder filling and those with severe symptoms of SUI are more likely to have low LPP.

Adipose-derived stem cells seeded on polyglycolic acid for the treatment of stress urinary incontinence.

To evaluate the effect and possible mechanism of suburethral tissue-engineered sling in an animal model of stress urinary incontinence (SUI). Adipose-derived stem cells (ADSCs) were obtained from the adipose tissues of rats. The differentiation potential, proliferation, and viability of rat ADSCs were evaluated after infecting these cells with a lentiviral vector-encoding green fluorescent protein (GFP). Next, GFP transfected ADSCs were seeded on polyglycolic acid (PGA) fibers to construct the tissue-engineered sling with the induction of 5-azacytidine (5-Aza). Afterward, the tissue-engineered slings were transplanted into a rat model of SUI that was established by vaginal balloon dilatation method and bilateral ovariectomy. Histology and the leak point pressure measurements were performed at 2months after tissue-engineered sling implantation. The ADSCs were found to be efficiently transfected with GFP, without any effects on proliferation, cell cycle and multi-differentiation potential. After been seeded on PGA fibers, ADSCs formed tissue-engineered slings in 4weeks of induction culture. Two months after implantation, the mean leak point pressure (LPP) was significantly increased in sling-treated rats compared with the balloon-injured ovariectomized rats. Immunofluorescence assay showed that some of the GFP expressing cells stained positive for muscle-specific markers. The newly suburethral tissue-engineered sling restores LPP in the rat model of SUI, which could be an effective treatment in future SUI therapy.

Role of urodynamics in stress urinary incontinence: A critical appraisal.

Introduction:Role of urodynamics prior to surgery of stress urinary incontinence (SUI) is under constant debate. Demonstration of the presence of detrusor overactivity is the only aspect that has been emphasized in the literature so far. We believe that there are number of other factors which may influence the evaluation and in turn the choice of surgical management and prediction of outcome of treatment. They are as follows: (1) Presence of voiding inefficiency, (2) asymptomatic detrusor overactivity, (3) and severity of SUI. These features may complicate the precise evaluation of patients of SUI. The main objective of this study is to analyze the dynamics of leakage and voiding using urodynamics. This study also aims at correlating these findings with clinical information.Materials and Methods:One hundred consecutive cases referred to our center for preoperative evaluation of SUI were recruited in the study prospectively. All patients were interrogated using International Consultation on Incontinence Questionnaire. All patients underwent complete urodynamic evaluation including uroflowmetry, filling cystometry, leak point pressure measurement, and pressure flow studies, according to Good Urodynamic Practice guidelines. Patients’ symptoms were correlated with urodynamic findings, with special emphasis on the presence of detrusor overactivity, severity of SUI, voiding efficiency, and presence of bladder outlet obstruction. Clinical information and urodynamic findings were correlated using Chi-square test.Results:There is a statistically significant correlation between the presence of symptoms of urge urinary incontinence and urodynamic findings of detrusor overactivity at P < 0.05. There is a statistically significant correlation between the symptoms of urge incontinence (in addition to SUI) and urodynamic findings of intrinsic sphincter deficiency at P < 0.05. Fifteen of 51 patients who did not have associated storage symptoms were found to have some degree of detrusor overactivity on urodynamic evaluation. There was no statistically significant correlation between asymptomatic cases of urge incontinence and incidental finding of detrusor overactivity at P < 0.05. There is no statistically significant correlation between the urodynamic findings of symptoms of voiding dysfunction and urodynamic findings, suggestive of the same value at P < 0.05.Conclusions:Urodynamic study in SUI has a potential of giving much more information than demonstration of Detrusor Overactivity alone. The predominant symptom of urge urinary incontinence can predictably diagnose detrusor overactivity in these cases. However, the incidence of asymptomatic detrusor overactivity remains as high as 15% and may have implication in postoperative results. This study clearly shows that there is a definite incidence of significant voiding dysfunction, which cannot be reliably evaluated without properly conducted pressure flow study. This factor may govern the choice of correct treatment which also predicts the outcome more reliably. Preoperative urodynamic study thus adds a dimension of precision to evaluation of the patients of SUI and may also influence technique and outcome measures in this group of patients.

A Method for Recording Urethral Pressure Profiles in Female Rats

AimsUrethral pressure profile (UPP) and leak-point pressure (LPP) measurements as well as external urethral sphincter (EUS) electromyography (EMG) and videourodynamic analyses are the primary methods for evaluating urethral function in humans. However, UPP recording in female rats, a widely used animal model, is challenging due to their small body sizes. This study reports a novel method for recording UPP in female rats.Materials and MethodsSeventeen anesthetized female rats were studied. LPP data for 14 rats were included. The other 3 rats were excluded because of death or abnormal urogenital organs. UPP curves were recorded using a modified water-perfusion catheter system, with the lateral hole facing the 3-, 6-, 9-, and 12-o’clock positions in a randomized sequence. LPP, functional urethral length (FUL) and maximum urethral closure pressure (MUCP) were analyzed.ResultsThe mean LPP was 64.39 ± 20.29 cm H2O. The mean FUL and MUCP values at the 3-, 6-, 9-, and 12-o’clock positions were 12.90 ± 1.20, 16.70 ± 1.95, 13.90 ± 2.42, and 11.60 ± 0.97 mm, respectively, and 38.70 ± 11.85, 33.90 ± 11.82, 37.40 ± 11.95, and 71.90 ± 23.01 cm H2O, respectively. The FUL at the 6-o’clock position and MUCP at the 12-o’clock position were significantly greater than those at the other 3 positions. The FUL and MUCP of repeated UPP recordings were not significantly different than those of the first recordings.ConclusionsUPP recording using a modified method based on a water-perfusion catheter system is feasible and replicable in female rats. It produces UPP curves that sensitively and appreciably reflect detailed pressure changes at different points within the urethra and thus provides opportunity to evaluate urethral structures, especially the urethral sphincter, in detail. These results may enhance the utility of female rat models in research of urinary sphincter mechanisms.

PD27-11 THERAPEUTIC EFFECTS OF A SELECTIVE ANDROGEN RECEPTOR MODULATOR, GSK2849466A ON STRESS URINARY INCONTINENCE IN OVARIECTOMIZED RATS

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Female Incontinence - Therapy I1 Apr 2015PD27-11 THERAPEUTIC EFFECTS OF A SELECTIVE ANDROGEN RECEPTOR MODULATOR, GSK2849466A ON STRESS URINARY INCONTINENCE IN OVARIECTOMIZED RATS Katsumi Kadekawa, Naoki Kawamorita, Philip Turnbull, Alan Russell, Sundeep Chandra, Joanna Barton, and Naoki Yoshimura Katsumi KadekawaKatsumi Kadekawa More articles by this author , Naoki KawamoritaNaoki Kawamorita More articles by this author , Philip TurnbullPhilip Turnbull More articles by this author , Alan RussellAlan Russell More articles by this author , Sundeep ChandraSundeep Chandra More articles by this author , Joanna BartonJoanna Barton More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.455AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although the etiology of stress urinary incontinence (SUI) in women is multifactorial, estrogen deficiency due to menopause is one of the major causes of SUI that induces atrophic and degenerative changes in urethral and pelvic floor muscles. Selective androgen receptor modulators (SARMs) selectively stimulate anabolic pathways of the androgen receptor in muscle and bone while sparing the androgenic effects typically seen with steroidal androgens. In this study, we examined the effect of a SARM (GSK2849466A) on the urethral continence mechanisms in a rat model of SUI induced by bilateral ovariectomy (OVX). METHODS Female nulliparous Sprague-Dawley rats with bilateral OVX were used. Rats were divided into 3 groups; sham operated (sham), vehicle-treated OVX (OVX-V), and GSK2849466A (0.03mg/kg/day, p.o.)-treated OVX (OVX-SARM) groups. At 2 weeks after OVX, vehicle or SARM treatment was started. After 4 weeks of treatment (6 weeks after OVX), rats were subjected to the evaluation of sneeze-induced continence reflex and sneeze-induced leak point pressure (S-LPP) measurements, followed by histological analyses of urethral tissues. RESULTS Urethral baseline pressure (UBP) and the amplitude of urethral responses during sneezing (AURS) were significantly decreased in the OVX-V group (n=11) by 46% and 38%, respectively, compared to the sham group (n=8). In the OVX-SARM group (n=11), UBP and AURS were significantly increased by 64% and 74%, respectively, compared to the OVX-V group. Fluid leakage was observed with S-LPP values of 59.8 □} 9.5 cmH2O during sneezing in all rats of the OVX-V group (n=8) whereas sham rats (n=8) did not leak during sneezing. In the OVX-SARM group (n=8), fluid leakage during sneezing was observed with a higher S-LPP value (82.9 cmH2O) in only 1 out of 8 rats (12.5%). Also, the OVX-SARM group had hypertrophy/reversal of atrophy of striated and smooth muscles in urethral transverse sections, compared to the OVX-V group. CONCLUSIONS These results indicate that ovariectomy significantly impairs urethral continence function after 6 weeks, and that SARM treatment restores the reductions in UBP, AURS and SLPP accompanied with urethral muscle hypertrophy, leading to the prevention of SUI. Based on our previous studies, UBP and AURS parameters are predominantly correlated to urethral smooth and striated muscle activity, respectively. Our current studies show that SARMs could be effective for the treatment of SUI by enhancing smooth and striated muscle mediated urethral function under stress conditions such as sneezing. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e575-e576 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katsumi Kadekawa More articles by this author Naoki Kawamorita More articles by this author Philip Turnbull More articles by this author Alan Russell More articles by this author Sundeep Chandra More articles by this author Joanna Barton More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...