Comparison of the urethral properties of the female guinea pig and rat

AIMS: The main focus of this study was to profile and compare urethral function in the female guinea pig and rat, and to characterize urodynamically distinctive patterns in the micturition cycle of the two species. This exercise aimed to investigate potential species-related differences and determine a suitable animal model for the human urethra. MATERIALS & METHODS: Female Dunkin-Hartley guinea pigs (400-500 g) and Sprague-Dawley rats (200-300 g) were used throughout the study. For in vitro experiments urethral rings were suspended vertically for isometric tension recording in 5 ml organ baths and drugs (phenylephrine 10(-4) M and carbachol 10(-4) M) were applied directly to the bathing solution. In vivo urethral pull-through and urodynamic studies were performed under urethane anesthesia, and phenylephrine (200 microg/kg) was administered during urethral pull-through experiments via the intravenous (i.v.) route. Urethral, bladder and arterial pressures, and external urethral sphincter electromyographic (EMG) spike activity were recorded simultaneously throughout. RESULTS: Organ bath studies coupled with in vivo pull-through experiments produced urethral profiles with distinct regional variations for both species. Urodynamic studies with the urethral probe fixed in the high pressure zones of the proximal urethra produced similar recordings in both species during bladder filling and marked differences during micturition. The guinea pig showed complete sphincteric inhibition immediately prior and during micturition as also seen in the human, whereas the rat exhibited high frequency bursts in EMG activity at this stage in the cycle. CONCLUSIONS: The EMG activity seen in the rat during micturition is presumably necessary for efficient voiding, thus the guinea pig is a more suitable comparative model for the human in relation to urethral properties during micturition.     

Selectivity of oxymetazoline for urethral pressure vs blood pressure in the anaesthetized female rabbit

OBJECTIVE: The aim of this study was to test alpha-adrenergic reference agonists for tissue selectivity in the urethra and to pharmacologically characterize the functional alpha-adrenoceptor type of the female rabbit urethra in vivo. MATERIAL AND METHODS: The effect of alpha-adrenergic agonists and antagonists on the urethral pressure was compared with that on blood pressure and heart rate measured simultaneously in the anaesthetized female rabbit. RESULTS: Oxymetazoline, NS-49, phenylephrine and phenylpropanolamine enhanced the urethral pressure in a dose-dependent manner. Phenylephrine and phenylpropanolamine also enhanced the blood pressure with significantly lower ED50 (dose that gives half of the maximal enhancing effect) values than for the urethral pressure. This was in contrast to oxymetazoline and NS-49. The ED50 values for oxymetazoline on urethral pressure, and systolic and diastolic blood pressure were 0.00067, 0.0030 and 0.0020 mg/kg, respectively. The ED50 values for NS-49 on urethral pressure, and systolic and diastolic blood pressure were 0.019, 0.21 and 0.18 mg/kg, respectively. Clonidine and UK 14,304 had no effect on urethral or blood pressure. The oxymetazoline-evoked increase in urethral pressure was inhibited by WB-4101 with an ID50 (dose that gives half of the inhibitory effect) significantly lower than that for rauwolscine. CONCLUSIONS: The results suggest that in the female rabbit in vivo activation of alpha1-adrenoceptors increased the urethral pressure. Phenylephrine and phenylpropanolamine, in contrast to oxymetazoline and NS-49, selectively enhanced blood pressure as compared with urethral pressure. Provided that the present results also have validity in humans, it would seem possible to develop urethra-selective drugs for treatment of stress incontinence with few or no cardiovascular side-effects.     

Small intestinal submucosa as a urethral coverage layer.

PURPOSE: Urethrocutaneous fistula is the most common complication of hypospadias surgery. Numerous techniques have been used to decrease the incidence of this complication and the use of biocompatible materials in surgery has expanded the options in difficult situations. We hypothesized that porcine small intestinal submucosa may be used as a coverage layer after urethral surgery. We evaluated the histological changes associated with small intestinal submucosa when used as a coverage layer over the urethra in a rabbit model. METHODS AND METHODS: We performed urethral surgery in 16 New Zealand White rabbits divided into 4 animals each in groups 1-sham operation with penile degloving only, 2-penile degloving and small intestinal submucosa patch placement, 3-urethrotomy without a patch and 4-urethrotomy with a small intestinal submucosa patch. The graft edges were marked with permanent suture at surgery for later identification. All rabbits were maintained for 6 weeks before sacrifice. The urethra of each animal was then serially sectioned and examined histologically. RESULTS: Histological examination of animals with an small intestinal submucosa patch revealed a foreign body tissue reaction with an infiltrate of histiocytes, giant cells and lymphocytes in the area of graft placement. There was no histological evidence of remaining small intestinal submucosa patch in any sections. The urethral mucosa healed normally in all cases in which it was disrupted. There was no evidence of acute or chronic inflammation in any group 1 or 2 nonsmall intestinal submucosa animals and none in the animals with a small intestinal submucosa graft in areas other than the former graft site. There were also no urethrocutaneous fistulas in any of the 8 rabbits that underwent urethrotomy. CONCLUSIONS: Small intestine submucosa provides an adequate coverage layer in the rabbit penis after urethrotomy. Histologically the foreign material did not alter normal healing of the urethral mucosa, although it did appear to cause an infiltration of histiocytes, giant cells and lymphocytes. Small intestinal submucosa has previously been studied as a scaffold on which tissue may be remodeled or may regenerate. Our study shows that small intestinal submucosa did not interfere with normal tissue healing in this animal model. When used as a urethral coverage layer, it appears to provide extra tissue between the urethra and skin. Small intestinal submucosa may potentially decrease the incidence of urethrocutaneous fistula after urethral surgery.     

Electromyography of the female urethral sphincter

Electromyography of the urethral striated sphincter gives information on the function of this muscle which consists of two structures: the intraurethral and periurethral sphincter. The types of electrode used to perform EMG of this sphincter are reviewed. The EMG findings of the peri- and intraurethral sphincters with empty bladder at rest and during maximal voluntary contraction are given as well as during bladder filling. Assessment of the urethral sphincter is described in different pathological situations. Methods and results of evoked potentials and nerve conduction measurements are also described in normal and pathological conditions.     

Porcine small intestinal submucosa graft for repair of anterior urethral strictures

OBJECTIVES: We evaluated porcine small intestinal submucosa (SIS) used in the treatment of inflammatory, iatrogenic, posttraumatic, and idiopathic strictures of bulbar and penile urethra. Midterm maintenance of urethral patency was assessed. METHODS: Fifty patients aged 45-73 yr with anterior urethral stricture underwent urethroplasty using a porcine SIS collagen-based matrix for urethral reconstruction. Stricture was localized in the bulbar urethra in 10 patients, the bulbopenile area in 31 cases, and in the distal penile urethra in nine patients. All patients received a four-layered SIS patch graft in an onlay fashion. A voiding history, retrograde and antegrade urethrography, and cystoscopy were performed preoperatively and postoperatively. Failure was defined as stricture confirmed on urethrogram. RESULTS: After a mean follow-up of 31.2 mo (range: 24-36 mo), the clinical, radiological, and cosmetic findings were excellent in 40 (80%) patients. Restricture developed in one of 10 bulbar, five of 31 bulbopenile, and four of nine penile strictures. These all occurred in the first 6 mo postoperatively. All patients with recurrences needed further therapy, but there has been no additional recurrence observed to date. No complications such as fistula, wound infection, UTI, or rejection were observed. CONCLUSIONS: Use of inert porcine SIS matrix appears to be beneficial for patients with bulbar and bulbopenile strictures. Midterm results are comparable to skin flaps and mucosal grafts.     

Physical properties of female urethral wall. Experimental method for determining relative degree of urethral wall stiffness

The female dog urethra was used in an experimental model to evaluate the relative degree of urethral wall stiffness in varying conditions. The model consisted of simultaneous monitoring of the pressure-volume relation and the external diameter changes during continuous distention of a closed urethral segment. The normal urethral response was analyzed, and changes as influenced by instrumental urethral dilation, urethral myotomy, and death were evaluated. The results indicated that appreciable increase in apparent compliance occurred under the previously mentioned experimental conditions. Although changes in specific compliance could not be reliably measured, observations on the diameter tracings suggested that a decrease would probably occur with no. 40 F. and larger-sized dilations.     

Post-traumatic female urethral reconstruction

Post-traumatic urethral damage resulting in urethrovaginal fistulas or strictures, though rare, should be suspected in patients who have unexpected urinary incontinence or lower urinary tract symptoms after pelvic surgery, pelvic fracture, a long-term indwelling urethral catheter, or pelvic radiation. Careful physical examination and cystourethroscopy are critical to diagnose and assess the extent of the fistula. A concomitant vesicovaginal or ureterovaginal fistula should also be ruled out. The two main indications for reconstruction are sphincteric incontinence and urethral obstruction. Surgical correction intends to create a continent urethra that permits volitional, painless, and unobstructed passage of urine. An autologous pubovaginal sling, with or without a Martius flap at time of reconstruction, should be considered. The three approaches to urethral reconstruction are anterior bladder flaps, posterior bladder flaps, and vaginal wall flaps. We believe vaginal flaps are usually the best option. Options for vaginal repair of fistula include primary closure, peninsula flaps, bilateral labial pedicle flaps, and labial island flaps. Outcomes are optimized by using exacting surgical principles during repair and careful postoperative management by an experienced reconstructive surgeon.     

小肠黏膜下脱细胞基质修复前尿道狭窄的疗效分析

目的 探讨小肠黏膜下脱细胞基质(small intestinal submucosa,SIS)修复前尿道狭窄的可行性和有效性.方法 2009年6月至2010年8月采用4层SIS补片修复治疗尿道狭窄患者18例.患者年龄20～69岁,平均38岁;尿道狭窄段3.5～7.0 cm,平均4.6 cm;术前最大尿流率1.5～5.5 ml/s,平均3.8 ml/s.术中按需将SIS(长4.0～7.5 cm,宽 2.0 cm)植入尿道背侧缺损处,5-0可吸收线将SIS间断固定在阴茎海绵体上,SIS两侧与已剪开的狭窄段尿道作连续缝合,两端分别与尿道断端作间断吻合.结果 手术过程顺利,术后恢复好.随访6～18个月,平均10个月,患者未发生感染、排斥反应等并发症.17例排尿通畅,最大尿流率14.0～44.0 ml/s,平均25.4 ml/s.尿道造影显示尿道通畅;术后4、6周尿道镜检查示SIS移植物与周围组织分界清楚;术后14周尿道镜检查SIS已降解,修复段尿道与周围组织间限消失,黏膜光洁完整,管腔无明显狭窄;植入SIS部位活检显示黏膜表层为上皮细胞.1例尿道下裂术后患者术后5个月出现轻度尿道狭窄症状,行尿道扩张治疗.结论 利用SIS修复尿道狭窄具有创伤小、抗感染力强的特点,可作为组织工程尿道修复重建材料修复部分尿道狭窄患者.

Abstract：

Objective To investigate the feasibility of using small intestinal submucosa (SIS) graft for the repair of anterior urethral strictures. Methods From June 2009 to August 2010, 18 men (mean age, 38 yrs) with anterior urethral strictures underwent urethroplasty using a four-layer SIS as an onlay patch graft. SIS was used to augment the urethral caliber at the stricture site. The mean stricture length was 4.6 cm (range 3.5 to 7 cm). The pre-operative mean maximal flow rate was 3.8 ml/s (range 1.5 to 5.5 ml/s). The required SIS grafts (4 to 7.5 cm long and 2 cm wide) were positioned into the urethrotomy defect and were spread-fixed to the corpora cavernosa using 5-0 polyglactin interrupted sutures. Two apices of the graft were sutured to the proximal and distal apices of the urethrotomy with 5-0 polyglactin interrupted stitches. The margins of the opened urethra were sutured to the SIS patch with 5-0 polyglactin running sutures. Results The mean follow-up period was 10 mon. (range 6-18 mon.). No postoperative complication, such as infection or rejection related to the use of heterologous graft material was observed. Seventeen patients voided well postoperatively with the mean peak urine flow of 25.4 ml/s (14-44 ml/s). Cystoscopy revealed that at four weeks and six weeks, the SIS graft was well distinguishable from the normal surrounding tissue; and at 16 weeks, the urothelium was regenerated and the biomaterial was not distinguishable from the normal surrounding tissue. The squamosal epithelium was seen in the histological examination of the grafts. The remaining one patient with failed hypospadias developed a slight urethral narrowing at five months post-operatively and needed sound dilatations. Conclusions SIS matrix appears to be a safe and effective reconstructive material in selected urethral reconstructions.     

Reconstruction of rabbit urethra with surgisis small intestinal submucosa

PURPOSE: To evaluate the efficacy of Surgisis, porcine small intestinal submucosa, in the reconstruction of iatrogenic urethral defects in rabbits. MATERIALS AND METHODS: Eight male white rabbits were enrolled in this protocol. A 2.5-cm segment of urethra was excised. One control consisted of a normal urethra. The other rabbits underwent urethroplasty with Surgisis and 6-0 Vicryl running suture. An 8F feeding tube was left in place to divert urine for 2 weeks after surgery. Retrograde urethrograms were performed to assess the patency of the urethras and to rule out fistula formation prior to sacrifice of the animals. The sacrifice protocol began with the control and a urethroplasty animal 6 weeks after surgery. The other rabbits were euthanized at 2-week intervals thereafter. RESULTS: Surgisis promoted epithelial regeneration in all cases. One animal developed a wound infection; this was associated with a small fistula at the proximal end of the anastomosis. Good cosmetic and functional results were documented. Retrograde urethrograms showed no stricture formation at the site of the anastomosis in six rabbits. The histopathologic examination showed complete regeneration of all urethral layers, almost indistinguishable from the normal urethra. CONCLUSION: Surgisis is an excellent material for urethral reconstruction in rabbits. It promotes regeneration of all the components of the host urethral layers and is biodegradable.     

Diagnosis and management of female urethral diverticulum

Female urethral diverticulum is a disorder that affects 1% to 6% of women. Women with diverticula may present with a variety of nonspecific genitourinary complaints, making the diagnosis challenging. Diagnosis is made by physical examination and can be confirmed with cystourethroscopy and/or radiographic imaging. Asymptomatic women can be managed conservatively, whereas treatment for symptomatic women usually involves a diverticulectomy. Potential complications from diverticulectomy include diverticulum recurrence, de novo stress incontinence, urethrovaginal fistula, urethral stricture, and recurrent urinary tract infections. This article reviews the etiology, differential diagnoses, evaluation, and management of female urethral diverticula.     

Evaluation and management of female urethral diverticulum

The urethral diverticulum has many varied presentations; therefore, ultimate diagnosis may be difficult. Until recently, radiographic evaluation was difficult to perform, was uncomfortable for the patient, and had poor sensitivity. The increasingly widespread use of magnetic resonance imaging coupled with heightened awareness of the problem has enhanced the overall detection of urethral diverticula. Management is still primarily surgical and entails proper anatomical identification of the defects that cause the diverticulum, so subsequent reconstruction can be performed easily and with minimal morbidity.     

Contemporary evaluation and management of the female urethral diverticulum

We are in agreement with Davis and Telinde, who state, "The most important single diagnostic instrument for the discovery of suburethral diverticula is the high index of suspicion" [25]. The key to successful treatment of a female diverticulum is not only in the surgical management but also in the identification and evaluation of patients who present with a myriad of symptoms. It is our responsibility to include urethral diverticula in the differential diagnoses before the labels of interstitial cystitis, urethral syndrome, or urgency frequency syndrome are misplaced. The diagnosis may be elusive and the pathology difficult to identify on physical examination. However, if the index of suspicion is high and the proper radiologic imaging studies are gathered, then the correct diagnosis will often be made. The evaluation of the female urethral diverticulum has evolved greatly over the past several years. However, once appropriate diagnosis is made, the management scheme is fairly straightforward. Strict adherence to principles of surgical reconstruction allows one to eradicate the diverticulum while simultaneously preventing complications and recurrences.     

Physiologic properties of small intestine submucosa

BACKGROUND: Porcine small intestine submucosa (SiS) has been introduced as a bioprosthesis in herniorrhaphy. This study evaluates in vivo properties of SiS that would affect clinical use. MATERIALS AND METHODS: Twelve pigs underwent implantation of SiS (perforated and nonperforated) on the peritoneal surface. Gross characteristics were evaluated and random samples harvested for histological study at 2 (n = 6) and 8 (n = 6) weeks. Collagen deposition was determined by polarized microscopy. Neovascularity (percent area blood vessels, %A(bv)) was determined by immunohistochemical staining with a polyclonal CD-31 antibody. RESULTS: Perforated SiS had a higher density of capillary ingrowth compared with nonperforated at both 2 (5.6%A(bv) versus 1.4%A(bv), P < 0.05) and 8 weeks (6.0%A(bv) versus 1.6%A(bv), P < 0.05). Compared with 2 weeks, 8-week SiS had a larger proportion of incorporation (25% versus 83%, P < 0.05) and new collagen deposition (50% versus 94%, P < 0.05). Significant contraction was observed in SiS 8 weeks after implantation (preimplant area 98 cm2 versus post-implant area 50 cm2, P < 0.05). CONCLUSION: SiS incorporated well 8 weeks after implantation, with deposition of new collagen. Perforated SiS demonstrated a more rapid and greater amount of neovascularity. The degree of contraction suggests that larger areas of SiS should be selected for herniorrhaphy than would be necessary if synthetic materials were used.