Characterization of pressor and visceromotor reflex responses to bladder distention in rats: sources of variability and effect of analgesics

PURPOSE: We assessed the usefulness of cardiovascular and visceromotor responses to bladder distention as measures of acute visceral nociception in rats by determining the reliability of these responses. MATERIALS AND METHODS: Halothane anesthetized male and female Sprague-Dawley rats were acutely instrumented with tracheal, jugular venous, carotid arterial and bladder cannulas. Wires were inserted into the abdominal musculature to enable myoelectrical activity measurement. Anesthesia was decreased until flexion reflexes were present. Repeat phasic and graded bladder distention was administered, and arterial blood pressure and abdominal electromyography activity were continuously monitored. We determined the effects of gender, vaginal smear estrous cycle stage and drug treatment on the measured responses. RESULTS: Bladder distention produced reliable pressor and visceromotor (abdominal contractile) responses. There was great inter-animal variability in response vigor but good reproducibility was noted within individual animals. During slow bladder filling bladder contractions were not noted at this level of anesthesia. Sex differences included a more vigorous reflex response in females than in males, which was most vigorous in females in proestrus. Repeat bladder distention led to increasingly vigorous pressor responses and the improved reliability of visceromotor responses. Intravenous morphine and lidocaine dose dependently inhibited the reflex responses. CONCLUSIONS: Pressor and visceromotor responses to bladder distention in halothane anesthetized rats are reliable measures of acute bladder nociception that may prove useful for analgesic screening and in studies of hormonal effects on nociception.     

Prevalence of postoperative bladder distension and urinary retention detected by ultrasound measurement

Background. Postoperative bladder distension and urinary retentionare commonly underestimated. Ultrasound enables accurate measurementof bladder volume and thus makes it possible to determine theprevalence of postoperative bladder distension. Methods. Using ultrasound, we measured the volume of the bladdercontents at the time of discharge from the recovery room in177 adult patients who had undergone thoracic, vascular, abdominal,orthopaedic or ENT surgery. Results. Forty-four per cent of the patients had a bladder volume>500 ml and 54% of the 44%, who had no symptoms of bladderdistension, were unable to void spontaneously within 30 min.The risk factors for urinary retention were age >60 yr (oddsratio (OR) 2.11, 95% confidence interval (CI) 1.01–4.38),spinal anaesthesia (OR 3.97, 95% CI 1.32–11.89) and durationof surgery >120 min (OR 3.03, 95% CI 1.39–6.61). Conclusion. Before discharge from the recovery room it seemsworthwhile to systematically check the bladder volume with aportable ultrasound device in patients with risk factors. Br J Anaesth 2004; 92: 544–6     

Experimental models of reflex contractile activity in the rabbit bladder

We were able to produce two highly reproducible experimental models (in the rabbit) that demonstrated a high degree of reflex bladder contractile activity. In one model, a somatovesical reflex was induced by touching or pinching the perineal area. This reflex may be organized through a neurogenic reflex at the spinal level. In another model, rhythmic bladder contractions were produced by distal urethral constriction in the absence of bladder distension. These rhythmic contractions were thought to be due to a supraspinal reflex. In both types of contractile reflexes, intravenous administration of hexamethonium inhibited the reflex contractile activity virtually completely, intravenous atropine inhibited over 90% of the induced contractile activity, thus suggesting that these contractions were mediated reflexly through cholinergic stimulation. These two models of reflex bladder contractions should be useful for the study of hyperreflexic bladders.     

Sympathetic inhibition of reflex activation of bladder motility during filling at a physiological-like rate in urethane anaesthetized rats

The mean volume of saline (infused at a physiological-like rate) required to elicit neurogenic rhythmic contractions of the detrusor muscle (micturition threshold) in urethane anaesthetized rats was reduced by reserpine pretreatment, as well as by chemical (6-hydroxydopamine) or surgical sympathectomy (bilateral section of the hypogastric nerves). Propranolol pretreatment had no significant effect on micturition threshold but increased the intraluminal pressure at which the rhythmic contractions occurred. In spinal rats (T12L1) a flat pressure volume curve was obtained with only a minor phasic contractile activity. Propranolol administration or bilateral section of the hypogastric nerves significantly increased the intraluminal pressure response to saline filling in spinal rats. Topical tetrodotoxin increased the intraluminal pressure response to saline filling in control spinal rats but not following propranolol administration or bilateral section of the hypogastric nerves. These findings provide evidence for a sympathetic inhibition of the reflex activation of the detrusor muscle in response to a physiological-like filling of the urinary bladder.     

Partial outlet obstruction induces chronic distension and increased stiffness of rat urinary bladder

In order to identify the passive properties of the bladder during filling, we measured cystometrograms (CMGs) of rat urinary bladders that had been outlet obstructed for 6 weeks and age-matched controls in conscious, unrestrained animals and in fully relaxed whole bladders in an organ bath. In the organ bath, each bladder was allowed to empty passively at zero transmural pressure. The volume remaining was labelled zero pressure volume (ZPV) and was used as the reference volume to normalize contained volume, deriving wall stretch. Increased ZPV implies that the bladder contains more urine at low stresses and therefore is more distended. In awake animals, the obstructed bladder CMGs showed spontaneous contractions. The pressures between contractions were similar to those in CMGs performed in the organ bath, suggesting that passive properties determine the minimum pressures during filling in vivo. The ZPV of the obstructed and control bladders was 1.07 ± 0.12 ml and 0.07 ± 0.01 ml, respectively. The differences were significant (P < 0.01). The ZPV correlated with bladder weight and thus with degree of hypertrophy. Under conditions when weight cannot be determined, e.g., clinically, ZPV may provide a useful measure of the degree of chronic distension and bladder hypertrophy. The pressure-volume curves of the obstructed bladder CMGs in vitro varied between preparations. However, when pressure-volume was converted to stress-stretch using the law of Laplace, the obstructed bladders were all significantly stiffer than the controls. We confirmed this result by step-stretching relaxed bladder strips. The obstructed bladder strips again demonstrated stiffer stress-stretch curves than the controls. © Wiley-Liss, Inc.     

Urodynamic evaluation of the bilharzial urinary bladder

Urodynamic evaluations of 63 male bilharzial patients and 25 normal males were included in the present work. According to the uroflowmetric parameters, patients were classified into two groups: those with normal voiding (38 patients) and those with impaired voiding (25 patients). Fluid cystometry followed by a micturition study were conducted in all patients with impaired voiding, 14 patients with normal micturition, and for two of the control group. The urodynamic data were computed and analyzed. Nineteen patients with bilharzial calcification of the urinary bladder underwent the same urodynamic evaluation. No urodynamic differences were found between the control group, the patients with normal voiding, and the patients with bilharzial bladder calcification. Patients with impaired voiding showed a significantly lower peak flow and longer micturition time; the voiding pressures and the abdominal contribution (%) were also significantly higher. Three factors were associated with impairment of micturition in our patients: (1) bladder outlet obstruction, (2) hypoactive detrusor, and () high-grade vesicoureteral reflux.     

Influence of temperature on urethra to bladder micturition reflex in the awake ewe

AIMS: The flow of fluid along the urethra is known to facilitate detrusor contraction during micturition. This reflex, previously described in awake ewes, helps to achieve complete bladder emptying. In anesthetized cats, another urethra to bladder reflex involving urethral cold receptors has been described. The aim of this study was to investigate whether the urethral reflex first described in awake ewes could also be temperature-dependent. METHODS: Experiments were performed on 10 healthy ewes. Urethral flows were performed by injecting 10 ml saline (ranging from 17 to 43 degrees C) at the level of the proximal urethra. Catheterization of the bladder was performed so that detrusor pressure was continually recorded during the experiments. RESULTS: Urethral flows using body temperature saline (37-39 degrees C) consistently evoked detrusor contraction. Urethral flows using saline at temperatures between 40 and 43 degrees C induced detrusor contractions that were not significantly different from those observed at 37-39 degrees C. Urethral flows using saline at temperatures below 37-39 degrees C (17-36 degrees C) resulted in a weaker or absent detrusor contraction. CONCLUSIONS: In ewes, we have shown that urethral to bladder micturition reflex involving mechanoreceptors is decreased at temperatures below the physiological range. It is suggested that transient receptor potential vanilloid cation channels (e.g., TRPV4 which is activated by sheer/stress flows at near-body temperature) could be involved in this urethra to bladder reflex. In humans, this reflex has hardly been described and is still a matter of debate. Our results reinforce that its full investigation may require systematic use of a range of saline flows at different temperatures.     

人工体神经-内脏神经反射弧治疗脊髓脊膜膨出患者大小便功能障碍

目的 :建立“人工体神经 内脏神经反射弧”(简称人工反射弧 )治疗脊柱裂脊髓脊膜膨出患者大小便功能障碍。方法 :对 30例大小便功能障碍的脊髓脊膜膨出患者 ,手术建立人工反射弧。进行术前与术后 6～ 1 8个月的尿动力学比较。结果 :30例中 1 3例获得了至少 1年的随访。 7例无反射型患者中 4例获得控尿和自主排尿功能 ,尿失禁消失 ,排尿间隔期逐渐延长至 3h以上 ,逼尿肌压由 (1 .37± 0 .78)kPa(1kPa =0 .0 98cmH2 O)增至(3.1 4± 1 .6 7)kPa ;6例高反射型患者全部于术后 1年左右恢复可控排尿 ,剩余尿逐渐减至 (2 2± 1 5 )ml,充盈性尿失禁消失。 1 0例获得膀胱功能控制者 ,直肠功能转为基本正常。下肢功能损伤较小。结论 :人工反射弧能安全有效地治愈先天性脊髓脊膜膨出所致大小便失禁     

Critical evaluation of the problem of chronic urinary retention after orthotopic bladder substitution in women

PURPOSE: We studied the possible causes of chronic retention after radical cystectomy and orthotopic bladder substitution in women. MATERIALS AND METHODS: Between January 1995 and January 2001, 136 women with a mean age plus or minus standard deviation of 52 +/- 8 years underwent standard radical cystectomy and orthotopic substitution for organ confined bladder cancer. Videourodynamics, pelvic floor electromyography, pelvic floor magnetic resonance imaging and pan-endoscopy were done. In the last 37 cases some technical modifications were adopted to circumvent the development of chronic urinary retention. RESULTS: One woman died postoperatively of massive pulmonary embolism. Of the 100 patients evaluable at a mean followup of 36 months 95 were continent in the daytime, 86 were continent at night, 2 were completely incontinent and 16 were in chronic retention. Videourodynamics showed that retention was mechanical in nature due to the pouch falling back in the wide pelvic cavity, resulting in acute angulation of the posterior pouch-urethral junction. In addition, herniation of the pouch wall through the prolapsed vaginal stump was observed in most cases. Pelvic floor electromyography demonstrated complete pelvic floor silence during voiding. No abnormality of the pelvic floor or rhabdosphincter was noted on magnetic resonance imaging. Pan-endoscopy showed a normal urethra with no urethroileal stricture. A 4 mg. dose of the alpha1-adrenergic blocker doxazosin daily was ineffective, excluding the possibility that sprouting from adjacent adrenergic neurons into the denervated proximal urethral muscles may have been the cause of this problem. After omental packing behind the pouch, suturing of the peritoneum on the rectal wall to the vaginal stump, suspension of the latter by the preserved round ligaments and suspension of the pouch near its dome to the back of the rectus muscle at cystectomy the incidence of chronic retention decreased from 18.7% (14 of 75 cases) before to 8% (2 of 25) after modifications. Furthermore, after vaginal wall descent was mechanically corrected by a pessary there was significant improvement in evacuation. CONCLUSIONS: Strong evidence was provided that chronic urinary retention after orthotopic substitution is due to anatomical rather than to functional or neurogenic reasons. Modifications to increase back support of the pouch with ventral suspension near its dome and support the vaginal stump are recommended to avoid this complication.     

Modulation of the micturition reflex pathway by intravesical electrical stimulation: An experimental study in the rat

Intravesical electrical stimulation (IVES) is used clinically to improve bladder evacuation in patients with inadequate micturition contractions. The procedure involves field stimulation of Aδ bladder mechanoreceptor afferents resulting in a prolonged enhancement of the micturition reflex. The aim of the present experimental study in the rat was to identify the site for this neuromodulation, whether it was due to sensitization of bladder mechanoreceptors, to enhancement of transmission in the central micturition reflex pathway, or to improved effectiveness of the peripheral motor system of the bladder. The experiments were performed on female rats, anesthetized by α-chloralose. Multi-unit afferent or efferent activity was recorded from bladder pelvic nerve branches during repeated cystometries before and after IVES. The specific antagonist CPPene was used to block central glutaminergic receptors of NMDA type. Micturition threshold volume decreased significantly after IVES. The afferent threshold volume, peak response, and pressure sensitivity were unchanged as were the peak efferent activity and bladder contractility. There was no efferent activity until just before the micturition contraction. The IVES-induced decrease in micturition threshold was blocked by prior administration of the NMDA (N-methyl-d -aspartic acid) antagonist CPPene (3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid). The findings indicate that the IVES-induced modulation of the micturition reflex is due to an enhanced excitatory synaptic transmission in the central micturition reflex pathway. The observed modulation may account for the clinical beneficial effect of IVES treatment. Neurourol. Urodynam. 17:543–553, 1998. © 1998 Wiley-Liss, Inc.     

Pediatric urinary incontinence: evaluation of bladder wall wraparound sling procedure

PURPOSE: In 1996 a surgical procedure for sphincter deficiency was reported in patients with neurogenic urinary incontinence. To our knowledge we report the first series that assesses this procedure since it was initially described. MATERIALS AND METHODS: Seven female and 7 male patients with spinal dysraphism and neurogenic intrinsic sphincter deficiency underwent surgery between 1997 and 2005. All patients had an associated poorly compliant or small capacity bladder. Patient age ranged from 8 to 22 years (mean 14) and all patients presented with persistent urinary incontinence despite intermittent catheterization and pharmacotherapy. Evaluation was based on clinical examination, as well as preoperative and postoperative urodynamic assessments. The surgical procedure involved wrapping a pedicle strip of anterior bladder wall around the bladder neck and fixing it on the pubic symphysis. Bladder augmentation cystoplasty was also routinely performed during the same procedure. RESULTS: Of 14 patients 13 were completely dry and 1 had stress incontinence. Followup was 2 to 8 years (mean 5). Postoperative urodynamic evaluation showed a maximum urethral pressure increase of 40%. We also observed an increase in bladder capacity of 105% and improved bladder compliance (7 ml/cm H(2)O preoperatively vs 35 ml/cm H(2)O postoperatively). CONCLUSIONS: The bladder wall wraparound sling procedure provides excellent results for continence in association with bladder augmentation.     

Ultrasonic evaluation of bladder neck position and mobility: The influence of urethral catheter,bladder volume,and body position

The influence of urethral catheter, bladder volume, and body position on the ultrasonic assessment of bladder neck position and mobility was evaluated in 24 incontinent women. The bladder neck position was described by two independent parameters: BS-distancc, from the bladder neck to the lower tip of the symphysis pubis. and the rotation angle between the BS-line and the symphyseal middline. Catheterisution resulted in apposition of the bladder neck towards the symphysis puhis, seen as a significant shortening of the BS-distance in postmenopausal women without estrogen replacement. The rotation angle was unaffected. Increasing the bladder volume to symptomatic-ally full resulted in increased capacity to withhold, since the rotation angle decreased 6.6°. Examination in the sitting position, compared to the supine resulted in bladder neck descent to a “lower level.” and the rotation angle increased in average 16°. Bladder neck mobility was unaffected by cathelerisalion and body position. Vaginal ultrasonic evaluation of bladder neck suspension is recommended to be performed without a catheter, with a comfortably full bladder in a convenient, but standardised examination position. © 1994 Wiley-Liss, Inc.     

Lack of effect following repeated in vivo exposure of the rabbit urinary bladder to urine from interstitial cystitis patients at low infusion volumes

We reported previously that substances in interstitial cystitis urine, when infused into the rabbit bladder, induce changes that resemble bladders of interstitial cystitis (IC) patients. Here we report our investigation of the effect of additional molecular weight subfractions of IC urine and lower infusion volume in this rabbit bladder bioassay. Urine was pooled from symptomatic IC patients, asymptomatic IC patients (in remission), and normal volunteers. Two fractions of 20× concentrated urine were obtained for each of the 3 groups: a 10–100-kD fraction and a fraction > 100 kD but <0.22 μm. Six rabbits per group were infused twice per week with 6 ml of 1 of these 6 urine fractions or saline as a control. After 6 weeks, each rabbit was cystoscoped before and after hydrodistension, bladder capacity and urea permeability were determined, and the bladder was removed for histologic examination. A questionnaire revealed a significant difference (P < 0.01) regarding voiding symptom severity between symptomatic IC patients and both normal volunteers and IC patients in remission. There was no statistically significant difference among groups of rabbits in cystoscopic bladder appearance, bladder capacity, urea permeability, or bladder histology. If a urine-borne factor is in part responsible for IC symptoms, the rabbit bladder must be filled with urine to near capacity to be able to detect a difference between IC and normal urine in this rabbit bladder bioassay. Neurourol. Urodynam. 17:147–152, 1998. © 1998 Wiley-Liss, Inc.     

The basis for drug treatment of the overactive bladder

 The normal bladder functions, storage and elimination of urine, are dependent on neural circuits in the brain and spinal cord that coordinate the activity of the detrusor and that of the smooth and striated muscles of the outflow region. Disturbances at different levels may cause the overactive bladder (OAB) syndrome, characterized by urge, frequency and urge incontinence. Knowledge about the mechanisms controlling both normal and abnormal micturition is mandatory for the detection of targets for pharmacological intervention. Such targets may be found in the central nervous system (CNS) or peripherally. Several CNS transmitters can modulate voiding, but few drugs with a defined CNS site of action have been demonstrated to be clinically useful. Traditionally, drugs for treatment of OAB have had a peripheral site of action. Antimuscarinics are still the gold standard, but their wellknown side effects have focused interest on other modalities of treatment. Promising preclinical results have been obtained for some principles, but so far there are few positive clinical proof of concept studies available.     

A model for both the passive and active properties of urinary bladder tissue related to bladder function

Herein we propose a new mechanical model for interpretation of volume-pressure relationships of the bladder in both the collection and in the evacuation phase. Contractile tissue is ascribed plastic properties. The static volume-pressure relation is related to a plasto/contractile-elastic tissue component. In contrast to other models, the elastic element in series with the contractile element corresponds to tissue elasticity, which also determines the static volume–pressure relation. Viscoelasticity is more relevant in the evacuation phase than in the collection phase.