Redefining urine output thresholds for acute kidney injury criteria in critically Ill patients: a derivation and validation study.

INTRODUCTION: The current definition of acute kidney injury (AKI) includes increased serum creatinine (sCr) concentration and decreased urinary output (UO). Recent studies suggest that the standard UO threshold of 0.5 ml/kg/h may be suboptimal. This study aimed to develop and validate a novel UO-based AKI classification system that improves mortality prediction and patient stratification. METHODS: Data were obtained from the MIMIC-IV and eICU databases. The development process included (1) evaluating UO as a continuous variable over 3-, 6-, 12-, and 24-h periods; (2) identifying 3 optimal UO cutoff points for each time window (stages 1, 2, and 3); (3) comparing sensitivity and specificity to develop a unified staging system; (4) assessing average versus persistent reduced UO hourly; (5) comparing the new UO-AKI system to the KDIGO UO-AKI system; (6) integrating sCr criteria with both systems and comparing them; and (7) validating the new classification with an independent cohort. In all these steps, the outcome was hospital mortality. Another analyzed outcome was 90-day mortality. The analyses included ROC curve analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and logistic and Cox regression analyses. RESULTS: From the MIMIC-IV database, 35,845 patients were included in the development cohort. After comparing the sensitivity and specificity of 12 different lowest UO thresholds across four time frames, 3 cutoff points were selected to compose the proposed UO-AKI classification: stage 1 (0.2-0.3 mL/kg/h), stage 2 (0.1-0.2 mL/kg/h), and stage 3 (< 0.1 mL/kg/h) over 6 h. The proposed classification had better discrimination when the average was used than when the persistent method was used. The adjusted odds ratio demonstrated a significant stepwise increase in hospital mortality with advancing UO-AKI stage. The proposed classification combined or not with the sCr criterion outperformed the KDIGO criteria in terms of predictive accuracy-AUC-ROC 0.75 (0.74-0.76) vs. 0.69 (0.68-0.70); NRI: 25.4% (95% CI: 23.3-27.6); and IDI: 4.0% (95% CI: 3.6-4.5). External validation with the eICU database confirmed the superior performance of the new classification system. CONCLUSION: The proposed UO-AKI classification enhances mortality prediction and patient stratification in critically ill patients, offering a more accurate and practical approach than the current KDIGO criteria.

Development and construction of an open-platform, open-source low-cost portable uroflowmeter: The OpenFlow device.

BACKGROUND: Uroflowmetry is useful to screen for and manage many voiding disorders. Home-based uroflowmetry might better represent the patient's true voiding pattern and be more widely adopted if an accurate low-cost portable device was available. OBJECTIVE: Development and initial evaluation of an open-platform, open-source low-cost portable uroflowmeter. MATERIALS AND METHODS: We designed and built an uroflowmeter comprising of a load cell and digital memory card unit connected to a programmable microcontroller board mounted upon a 3D printed frame. It generated date-stamped tables which were processed and plotted. Twenty urologists were recruited to assess the device. Each participant received the equipment that was returned, along with a bladder diary, after at least 24 consecutive hours of homemade uroflowmetry recording. Additionally, were assessed with the International Prostatic Symptom Score (I-PSS) and Peeling diagram, whereas the device's ease of use, robustness, and portability were evaluated with a Likert-type questionnaire. Two experienced urodynamicists independently evaluated the tracings' quality rated with a 3° ordinal scale: (1) Interpretable without artifacts; (2) Interpretable with artifacts; (3) Uninterpretable. RESULTS: Participants' median age was 36.6 years old, none having an I-PSS > 5 or Peeling > 2. Overall 138 voidings were recorded (77 daytime, 61 nightly episodes). The device's ease of use, robustness, and portability obtained maximum score in 80% of evaluations. Most (98%) of the tracings were considered interpretable. Limitations included its small study population and short monitoring times. CONCLUSION: The construction of a cheap (<50 USD), accurate user-friendly portable uroflowmeter proved feasible, which could facilitate access to portable uroflowmetry.

Defining bladder outlet obstruction and detrusor underactivity in females with overactive bladder: Are we forgetting about the free uroflowmetry?

INTRODUCTION: Both detrusor underactivity (DU) and bladder outlet obstruction (BOO) can coexist in patients with overactive bladder. Definitions of both DU and BOO are based on pressure-flow study (PFS) data. However, invasive urodynamics study can differ from a natural micturition, in fact, discrepancies between free uroflowmetry (UFM) and PFS have been largely described. Our goal is to assess the correlation of free-flowmetry and PFS among patients with OAB and to evaluate how different definitions of DU/BOO are able to discriminate patients with different free UFMs. METHODS: A retrospective review of urodynamics performed at a single institution was conducted. Females with OAB who voided more than 150 mL in both UFM and PFS were included. Parameters from both voiding episodes were compared with nonparametric test. Two definitions of DU were applied; PIP1: Pdet@Qmax+Qmax < 30 and Gammie: Pdet@Qmax < 20 cmH2 O, Qmax < 15 mL/s, and BVE < 90% (Bladder voiding efficiency). Also, two definitions of obstruction were chosen; Defretias: Pdet@Qmax ≥25 cmH2 O and Qmax ≤ 12 mL/s and Solomon-Greenwell female BOO index ≥ 18. Patients who matched with each definition were compared to those who did not, to assess if any definitions were able to discriminate different noninvasive uroflowmetries. RESULTS: A total of 195 patients were included. Overall, mean age was 55 ± 12 years, 90.8% had mixed urinary incontinence, and 39% complained of at least one voiding symptom. Globally, Qmax and BVE correlated poorly between UFM and PFS, showing that most of the variation corresponded to a systematic error. Twenty-two individuals were found to have DU, they had a difference of 13 mL/s on both maximum flows. Fifty-four patients showed BOO, with a difference between their Qmax of 19 mL/s. Among the four definitions analyzed, only PIP1 and Defreitas were able to discriminate patients with actually a lower Qmax on the free UFM. CONCLUSIONS: Patients with overactive bladder seem to have a systematic discordance between the urine flow of the free and invasive studies. Current definitions of DU and BOO, which are based on the PFS parameters, are not consistently able to discriminate patients who actually void deficiently on the free UFM.

One-day voiding diary in the evaluation of Lower Urinary Tract Symptoms in children.

INTRODUCTION: Voiding diary (VD) is an important tool in the evaluation of children with voiding symptoms. Voiding frequency, maximal voided volume (MVV), average voided volume (AVV) and nocturnal volume (NV) can be extracted and are valuable in diagnosing and monitoring these disorders. Recently, ICCS has reduced the period of data recording on VD from 3 to 2 days.We hypothesized that one day voiding diary would be enough for guiding treatment. MATERIALS AND METHODS: Children with overactive bladder (OAB) and primary monosymptomatic enuresis (PMNE) were oriented to fulfill a 3-day VD. Data obtained from VD were evaluated for the first day (1dVD), the first two days (2dVD), and all 3 days (3dVD) and compared according to the MVV, AVV, frequency, NV and expected bladder capacity (EBC). The Friedman, Student's t test and the Fisher's exact was used. ANOVA was used for multiple comparisons. We also used Pearson correlation test. RESULTS: Ninety-eight children were included, 59 had PMNE and 30 OAB. Frequency, AVV and VN were similar regardless how many days the voiding episodes were recorded. Only MVV was higher by a mean of only 32 mL on 3dVD compared to 1dVD. A 1dVD has a sensitivity of 93,9% and a positive likelihood ratio of 2.2. As for the correlation of MVV and EBC it was observed that in 83% of children, MVV was lower than EBC. MVV corresponds to 67% and 69% of EBC in children with PMNE and OAB, respectively. CONCLUSION: We believe that 1dVD is sufficient to assess these children. It has a high sensitivity and good correlation to 3dVD in evaluating these children. Bladder capacity in this population, evaluated by maximum voided volume, was close to 68% of that obtained by the EBC.

Urodynamic profile of voiding in patients with pelvic organ prolapse after surgery: a systematic review with meta-analysis.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is a defect of the female pelvic floor. Stress urinary incontinence (SUI), urge urinary incontinence (UUI), and obstructive symptoms may occur in these patients. The objective of surgical treatment is to restore the anatomy and function of the pelvic floor; however, it may prompt urinary symptoms not present previously. We performed a systematic review and meta-analysis to determine urodynamic changes in patients undergoing surgical correction for POP. METHODS: PubMed and Cochrane databases were searched for studies that contained data from urodynamic evaluation before and after vaginal surgery for POP. The main urodynamic data collected were free uroflowmetry (maximum flow [Qmax], voided volume, and post-void residual volume [PVR]), cystometry (bladder capacity, presence of detrusor overactivity [DO], SUI or UUI, and Valsalva leak point pressure), and pressure × flow study (detrusor pressure at maximum flow [PdetQmax], Qmax, and PVR). RESULTS: A total of 22 studies were included (1,549 women). Patients had a significantly higher prevalence of DO before surgery (OR = 1.56; 95% CI = 1.06-2.29), and surgeries without sling placement demonstrated a tendency to ameliorate DO. Patients who did not receive a sling were more incontinent after surgery. Bladder-emptying parameters improved after surgery, with higher PdetQmax before surgery (IV = 3.23; 95% CI = 0.45-1.18). Patients who did not receive MUS presented a lower Qmax (IV = -3.19; 95%CI = -4.09 to -2.30) and a higher PVR (IV = 27.89; 95%CI = 15.68-40.1) before surgery. CONCLUSION: Correction surgery for POP yields better urodynamic emptying parameters, with a reduction in the prevalence of DO. In contrast, sling placement enhances obstructive parameters.

Continuous administration of leuprolide acetate improves urinary function in male rats with severe thoracic spinal cord injury.

AIMS: To determine if a continuous administration of leuprolide acetate (LA), a synthetic agonist for the gonadotrophin-releasing hormone receptor, facilitates the recovery of urinary function in spinal cord injured male rats. MAIN METHODS: Male Wistar rats were randomized into spinal cord injury (SCI; n = 7), SCI with continuous administration of LA for two weeks via implantation of a subcutaneous osmotic pump (SCI + LA; n = 7), Sham SCI (SH-SCI; n = 6) or no surgery (Intact; n = 6) groups. Micturition, hind-limb nociception and locomotor behaviors were analyzed before and after surgical procedures on days 7, 14, 21 and 28. After behavioral studies, electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies were performed in all groups. KEY FINDINGS: SCI significantly decreased frequency of voids and CMG parameters (p < 0.001), abolished the bursting activity of the EUS during CMG, significantly increased hind limb sensory threshold and decreased locomotor performance in comparison to the other groups (p < 0.001). Continuous LA treatment significantly increased the frequency of voids and improved CMG parameters (p < 0.001), exhibiting bursting EUS activity during CMGs, and enhanced locomotor performance in comparison to SCI rats (p < 0.001). SIGNIFICANCE: SCI severely affected behavioral and functional micturition processes, including sensory and locomotor functions. Systemic and uninterrupted treatment with LA improves the recovery of micturition behavior and the synergistic function of the EUS. Furthermore, sensory and locomotor responses were also improved in SCI rats. This procedure may have a therapeutic potential to facilitate urinary function recovery in patients with SCI.

Efficacy of intravaginal electrical stimulation with different treatment frequency in women with refractory idiopathic overactive bladder.

OBJECTIVE: The aim of this study is to evaluate the effect of intravaginal electrical stimulation (IVES) therapies with different treatment frequencies (two or five days in a week) added to bladder training (BT) on incontinence-related quality of life (QoL) and clinical parameters in women with refractory idiopathic overactive bladder (OAB). MATERIAL AND METHODS: Fifty-two women with refractory idiopathic OAB were randomized into two groups as follows: Group 1 (n:26) received BT and IVES, two times in a week, for 10 weeks and Group 2 (n:26) received BT and IVES five times in a week, for 4 weeks. IVES was performed 20 minutes in a day, a total of 20 sessions for both groups. Women were evaluated for incontinence severity (24h pad test), pelvic floor muscles strength (perineometer), 3-day voiding diary (frequency of voiding, nocturia, incontinence episodes, and the number of pads), symptom severity (OAB-V8), quality of life (IIQ-7), treatment success (positive response rate), cure/improvement rate and treatment satisfaction (Likert scale). RESULTS: There was no statistically significant differences in all parameters between the two groups at the end of the treatment. It was found that the treatment satisfaction scores, cure/improvement and positive response rates were not significantly different between two groups (p>0.05). CONCLUSION: We concluded that the application of IVES twice a week or 5 times a week added to BT were both effective on incontinence-related QoL and clinical parameters in women with refractory idiopathic OAB. These two IVES frequencies had similar clinical efficacy and patient satisfaction with a slight difference between them; 5 times per week IVES has a shorter treatment duration.

Dropped abdominal pressure at void in women.

INTRODUCTION AND HYPOTHESIS: "Dropped pabd at void" occurs when pabd decreases below the previous resting pressure during voiding time. We sought clinical factors associated with this phenomenon and evaluated whether its correction modifies the urodynamic diagnosis. METHODS: Retrospective cross-sectional study of non-neurological consecutive symptomatic women. The following definitions were used: "dropped pabd at void": decrease in pabd at Qmax ≥ 5 cmH2O; bladder outflow obstruction (BOO) (pdetQmax ≥ 25 cmH2O + Qmax ≤ 12 ml/s and female BOO index (pdetQmax - 2.2*Qmax) > 18; "low detrusor contraction strength": PIP1 (pdetQmax + Qmax) < 30. In patients with "dropped pabd at void", pdetQmax was corrected. RESULTS: A total of 360 women were analyzed. Ninety-five percent of the women had a variation in pabd at Qmax between -13 and 53 cmH2O. "Dropped pabd at void" was found in 100 women (27.8%). History of stress urinary incontinence (SUI) surgery was significantly higher (p = 0.016) and symptoms of mixed urinary incontinence were significantly lower (p = 0.030) in patients with "dropped pabd at void". On multivariate analysis only the history of SUI surgery maintained its significance (OR = 1.787 [95% CI: 1.058, 3.017], p = 0.030). When correcting pdetQmax in women with "dropped pabd at void", 2 or 5 patients lost BOO diagnosis (depending on how it was diagnosed) and 7 patients gained a "low detrusor contraction strength" diagnosis. CONCLUSIONS: Approximately one-quarter of women had "dropped pabd at void", which was associated with a history of SUI surgery. Correction of pdetQmax would lead to a 2.5% to 3.33% diagnostic modification.

[Moderate/severe hydronephrosis before ureteral double-j stent insertion is associated with less back pain during micturition.] / La hidronefrosis moderada/severa antes de la inserción del catéter ureteral doble J se asocia con menos dolor de espalda durante la micción.

OBJECTIVE: Symptoms related toureteral double-J stent are the most common complaintamong patients. Back pain during micturition isone of the most frequent but intensity and durationmay vary between them. This study aimed to assessthe relationship between hydronephrosis grade beforeureteral double-j stent insertion and back pain duringmicturition. PATIENTS AND METHODS: All consecutive patientsundergoing a ureteral double-j insertion secondaryto urolithiasis between 2017 and 2019 were prospectivelyenrolled. Hydronephrosis was assessed using aCT scan and was categorized according to renal pelvismeasure as 0-10 mm (low group), and ≥10 mm(moderate group). At one week postoperative, patientsymptoms were evaluated using the Spanish validatedversion of the Ureteral Stent Symptom Questionnaire(USSQ) and 10 cm visual analog scale (VAS). Meanscores for USSQ domains and mean VAS scores werecompared. RESULTS: 149 patients were included and evaluated.The mean age was 48.2±15.1 years. We found no significantdifferences in mean scores for each main domainin the USSQ or VAS. The presence of flank painduring micturition was present in 73.5% and 52.5 %for the low vs moderate hydronephrosis group respectively(p=0.01). Sub-analysis by gender was 78.7 % vs44.0 % (p=0.00) and 58.6% vs 66.6% (p=0.6) of low andmoderate group in men and women respectively.Analysis of the USSQ item score revealed thatthe moderate hydronephrosis group presented less''pain or discomfort when urinating,'' less ''presenceof back pain when urinating,'' less ''admission orprocedure because of discomfort,'' and less ''feelingabout reinsertion''. CONCLUSION: Patients in the moderate hydronephrosisgroup did not have significant advantagesin terms of voiding symptoms, pain, general health,sexual matters, or additional problems determined bythe USSQ or in VAS. However, sub-analysis reportedadvantages concerning pain and additional questions.Men with moderate hydronephrosis presented statisticallysignificantly less pain during micturition.

INTRODUCCIÓN Y OBJETIVO: Lossíntomas relacionados con el catéter ureteral doble-Json la queja más común en los pacientes. El dolor deespalda durante la micción es uno de los más frecuentes,pero la intensidad y la duración varían entre ellos.El objetivo de este estudio fue evaluar la relación entreel grado de hidronefrosis antes de la inserción del catéterureteral doble-J y el dolor de espalda durante lamicción. PACIENTES Y MÉTODOS: Se incluyeron prospectivamentetodos los pacientes consecutivos que sesometieron a la inserción de un catéter ureteral doblej debido a la urolitiasis entre 2017 y 2019. La hidronefrosisse evaluó mediante una tomografía computarizaday se clasificó según la medida de la pelvis renalcomo 0-10 mm (grupo bajo), y ≥10 mm (grupo moderado/severo). Una semana después de la operación,los síntomas del paciente se evaluaron utilizando laversión validada en español del Cuestionario de Síntomasdel Catéter Ureteral (USSQ) y la la escala visualanáloga (EVA) de 10 cm. Se compararon las puntuaciones medias de los dominios del USSQ y las puntuacionesmedias de la EVA. RESULTADOS: Se incluyeron y evaluaron 149 pacientes.La edad media fue de 48,2±15,1 años. No seencontraron diferencias significativas en las puntuacionesmedias de cada dominio principal en la USSQo la EVA. La presencia de dolor en el flanco durante lamicción estuvo presente en el 73,5% y el 52,5% parael grupo de hidronefrosis baja vs. moderada respectivamente(p=0,01). El subanálisis por género fue 78,7% vs 44,0 % (p=0,00) y 58,6 % vs 66,6 % (p=0,6) delgrupo de baja y moderada en hombres y mujeres respectivamente.El análisis de la puntuación de los ítems de laUSSQ reveló que el grupo de hidronefrosis moderadapresentó menos "dolor o molestia al orinar", menos"presencia de dolor de espalda al orinar", menos "admisióno procedimiento por molestia" y menos "sensaciónde reinserción". CONCLUSIÓN: Los pacientes del grupo de hidronefrosismoderada no ofrecen ventajas significativas encuanto a los síntomas de evacuación, el dolor, la saludgeneral, las cuestiones sexuales o los problemasdeterminados por el USSQ o en EVA. Sin embargo, elsubanálisis informó de ventajas relativas al dolor ypreguntas adicionales. Los hombres con hidronefrosismoderada presentaban un dolor estadísticamente significativodurante la micción.

Relationship between maximum voided volume obtained by bladder diary compared to contemporaneous uroflowmetry in men and women

ABSTRACT Introduction: The 24-hour bladder diary is considered to be the gold standard for evaluating maximum voided volume (MVV). However, we observed that patients often have a greater MVV during office uroflowmetry than that seen in the bladder diary. The purpose of this study is to compare these two non-invasive methods by which MVV can be determined - at the time of uroflowmetry (Q-MVV), or by 24hour bladder diary (BD-MVV). Materials and Methods: This was an Institutional Review Board approved retrospective study of patients evaluated for LUTS who completed a 24hour bladder diary and contemporaneous uroflowmetry. For Q-MVV, the patient was instructed to wait to void until their bladder felt full. Sample means were compared, and Pearson's correlations were calculated between the Q-MVV and BD-MVV data across the total sample, women, and men. Results: Seven hundred seventy one patients with LUTS completed bladder diaries. Of these, 400 patients, 205 women and 195 men, had contemporaneous Q-MVV. Mean BD-MVV was greater than mean Q-MVV. However, Q-MVV was larger in a sizable minority of patients. There was a weak correlation between BD-MVV and Q-MVV. Furthermore, there was a difference ≥50% between Q-MVV and BD-MVV in 165 patients (41%). Conclusions: The data suggest that there is a difference between the two measurement tools, and that the BD-MVV was greater than Q-MVV. For a more reliable assessment of MVV, this study suggests that both Q-MVV and BD-MVV should be assessed and that the larger of the two values is a more reliable assessment of MVV.

Evaluation of autonomic function in children and adolescents with overactive bladder

ABSTRACT Aims: To evaluate autonomic activity in children/adolescents with isolated overactive bladder. Materials and Methods: Descriptive, analytical, non-interventional, cross-sectional study conducted between February 2017 and January 2018 with individuals aged between 5 and 17 years old, with overactive bladder (OAB group) or asymptomatic (control). Neurological or anatomical abnormalities, diabetes mellitus and kidney failure constituted exclusion criteria. The DVSS and the Rome III questionnaire were applied, and heart rate variability (HRV) was assessed. The chi-square test, Student's t-test, ANOVA and the Mann Whitney U test were used in the statistical analysis. Results: 41 patients with OAB and 20 controls were included. In the OAB group, there were more girls (p=0.23), more overweight/obese and constipated patients. The DVSS score was higher in the OAB group. HRV showed a higher heart rate variability at the frequency domain and LF/HF variation in the control group (p=0.02 and p=0.05 respectively). In the intergroup evaluation, LF (Hz) was predominant in the control group at the post-voiding evaluation moment (p=0.03). Conclusion: The control group demonstrated a physiological heart rate variation during the voiding process, with a predominance of sympathetic activity during urinary storage.

Time course for urethral neuromuscular reestablishment and its facilitated recovery by transcutaneous neuromodulation after simulated birth trauma in rats.

The aims of the study were to determine the time-course of urinary incontinence recovery after vaginal distension (VD), elucidate the mechanisms of injury from VD leading to external urethral sphincter (EUS) dysfunction, and assess if transcutaneous electrical stimulation (TENS) of the dorsal nerve of the clitoris facilitates recovery of urinary continence after VD. Rats underwent 4-h VD, 4-h sham VD (SH-VD), VD plus 1-h DNC TENS, and VD plus 1-h sham TENS (SH-TENS). TENS or SH-TENS were applied immediately and at days 2 and 4 post-VD. Micturition behavior, urethral histochemistry and histology, EUS and nerve electrophysiology, and cystometrograms were evaluated. VD induced urine leakage and significantly disrupted EUS fibers and nerve-conduction (VD vs SH-VD group; p < 0.01). Urine leakage disappeared 13 days post-VD (p < 0.001). Structural and functional recovery of EUS neuromuscular circuitry started by day 6 post-VD, but did not fully recover by day 11 post-VD (p > 0.05). TENS significantly decreased the frequency of urine leakage post-VD (days 5-7; p < 0.01). We conclude that rat urinary continence after VD requires 2 weeks to recover, although urethra structure is not fully recovered. TENS facilitated urinary continence recovery after VD. Additional studies are necessary to assess if TENS could be used in postpartum women.

Evaluation of autonomic function in children and adolescents with overactive bladder.

AIMS: To evaluate autonomic activity in children/adolescents with isolated overactive bladder. MATERIALS AND METHODS: Descriptive, analytical, non-interventional, cross-sectional study conducted between February 2017 and January 2018 with individuals aged between 5 and 17 years old, with overactive bladder (OAB group) or asymptomatic (control). Neurological or anatomical abnormalities, diabetes mellitus and kidney failure constituted exclusion criteria. The DVSS and the Rome III questionnaire were applied, and heart rate variability (HRV) was assessed. The chi-square test, Student's t-test, ANOVA and the Mann Whitney U test were used in the statistical analysis. RESULTS: 41 patients with OAB and 20 controls were included. In the OAB group, there were more girls (p=0.23), more overweight/obese and constipated patients. The DVSS score was higher in the OAB group. HRV showed a higher heart rate variability at the frequency domain and LF/HF variation in the control group (p=0.02 and p=0.05 respectively). In the intergroup evaluation, LF (Hz) was predominant in the control group at the post-voiding evaluation moment (p=0.03). CONCLUSION: The control group demonstrated a physiological heart rate variation during the voiding process, with a predominance of sympathetic activity during urinary storage.

Estrogens influence differentially on the pelvic floor muscles activation at somatovisceral reflexes involved in micturition of rabbits.

OBJECTIVE: To determine the estrogen-dependency of the bladder and urethral function and the coordinated activation of pelvic floor muscles (PFM) during micturition. METHODS: We allocated age-matched female rabbits to control, 1-month ovariectomized (OVX), and OVX plus 2-week estradiol benzoate (EB) groups to record cystometry, urethral pressure, and electromyograms of bulbospongiosus (Bsm), and pubococcygeus muscles (Pcm) simultaneously. We also measured serum estradiol levels and myofiber cross-sectional area. We assessed urodynamic and urethral variables, categorized the Bsm-Pcm activation patterns at storage and voiding phases, and obtained the power spectrum density of muscle activation around the voiding phase. We investigated the influence of ovarian hormones, in general, and the contribution of estrogen, particularly on the functions of the bladder, urethra, and PFM. Statistical significance was set at P < 0.05. RESULTS: Ovarian hormones influence the bladder, urethral, and PFM functions. The urodynamics analyses indicated estrogens contribute to voiding duration and, to a lesser extent, to the time between bladder contractions. Urethral pressure at closure (maximal pressure-to-maximal urethral pressure ratio) improved partially (8%, P < 0.05) in the OVX plus 2-week estradiol benzoate compared with OVX, but urethral resistance increased (∼1.9-fold, P < 0.05) compared with control rabbits. Our findings support that Pcm activity at voiding is estrogen-sensitive, albeit EB administration reduced it at storage resume, which relates to high urethral resistance. CONCLUSIONS: Ovariectomy impairs bladder and urethral pressures and Bsm and Pcm activation at micturition in anesthetized rabbits. Estrogen administration partially reverts some of these effects and influences Pcm activation.

Metformin abrogates the voiding dysfunction induced by prolonged methylglyoxal intake.

Methylglyoxal (MGO) is a reactive carbonyl species found at high levels in blood of diabetic patients. The anti-hyperglycemic drug metformin can scavenger MGO and reduce the formation of advanced glycation end products (AGEs). Here, we aimed to investigate if MGO-induced bladder dysfunction can be reversed by metformin. Male C57/BL6 mice received 0.5% MGO in drinking water for 12 weeks, and metformin (300 mg/kg, daily gavage) was given in the last two weeks. The bladder functions were evaluated by performing voiding behavior assays, cystometry and in vitro bladder contractions. MGO intake markedly elevated the levels of MGO and fluorescent AGEs in serum and reduced the mRNA expression and activity of glyoxalase (Glo1) in bladder tissues. Glucose levels were unaffected among groups. MGO intake also increased the urothelium thickness and collagen content of the bladder. Void spot assays in conscious mice revealed an increased void volume in MGO group. The cystometric assays in anesthetized mice revealed increases of basal pressure, non-voiding contractions frequency, bladder capacity, inter-micturition pressure and residual volume, which were accompanied by reduced voiding efficiency in MGO group. In vitro bladder contractions to carbachol, α,ß-methylene ATP and electrical-field stimulation were significantly greater in MGO group. Metformin normalized the changes of MGO and AGEs levels, Glo1 expression and activity, urothelium thickness and collagen content. The MGO-induced voiding dysfunction were all restored by metformin treatment. Our findings strongly suggest that the amelioration of MGO-induced voiding dysfunction by metformin relies on its ability to scavenger MGO, preventing its accumulation in blood.