Morphological aspects of the female pig bladder neck and urethra: quantitative analysis using computer assisted 3-dimensional reconstructions.

PURPOSE: To investigate whether the pig is a suitable model for studies of lower urinary tract function and dysfunction, we sought to determine the morphology of the female pig bladder neck and urethra. Computer assisted 3-dimensional (D) reconstructions from step serial histological sections were used for visualization of the spatial relationships between neighboring urethral wall components, and the quantification of these components in the bladder neck and along the urethra. MATERIALS AND METHODS: Step serial histological paraffin sections from the bladder neck and urethra of 6 female pigs, stained with Masson's trichrome, were used to generate computer assisted 3-D reconstructions using MacStereology (Ranfurly MicroSystems Ltd., Airdrie, United Kingdom) as the 3-D software package. RESULTS: The bladder neck and urethral anatomy revealed well defined smooth and striated muscle layers that varied in location, regional distribution and orientation. Circular smooth muscle was maximally developed in the mid urethra, at which point maximal urethral pressure was observed. The longitudinal smooth muscle layer appeared continuous with the detrusor, implicating a possible role in urethral shortening at the onset of voiding. A small circular and longitudinal striated muscle component was present in the distal urethra. CONCLUSIONS: Anatomical differences exist between the female pig and human bladder neck and urethra, which were successfully highlighted using computer assisted 3-D reconstructions from step serial histological paraffin sections.

The effect of bladder outflow obstruction on detrusor blood flow changes during the voiding cycle in conscious pigs.

PURPOSE: We monitored detrusor blood flow in pigs with bladder outflow obstruction. MATERIALS AND METHODS: Partial urethral obstruction was created in 9 immature, female large white pigs with an implanted ring, and 10 normal animals were used for comparison. Urodynamic parameters and detrusor blood flow were measured using chronically implanted access catheters and laser Doppler fibers. Repeated recordings were made from each animal while it was lightly sedated. RESULTS: The animals with implanted rings developed prolonged, high pressure voiding contractions in association with poor urinary flow, indicating bladder outflow obstruction, and had evidence of detrusor instability. In obstructed and normal animals detrusor blood flow was maintained during bladder filling. Elevated detrusor pressure during voiding significantly decreased blood flow to similar levels in each group. The duration of the ischemic period was much greater in obstructed animals. CONCLUSIONS: Bladder outflow obstruction is associated with repeated episodes of prolonged detrusor ischemia which may account for the biochemical and neuronal alterations in such bladders.

The contribution of cholinergic detrusor excitation in a pig model of bladder hypocompliance.

OBJECTIVE: To investigate the role of cholinergic excitation in mediating changes in detrusor compliance (manifested on conventional cystometry as an incremental rise in detrusor pressure as bladder volume increases) under conditions of propofol-sedation in the pig. Materials and methods Consecutive cystometrograms (CMGs) were obtained from eight female Large White pigs at a bladder filling rate of 50 mL/min. The first CMG was obtained while the pig was awake and unsedated. Two subsequent CMGs were obtained after light to moderate sedation with propofol (2-8 mg/kg/h) before and after the administration of intravenous atropine (0.02 mg/kg). RESULTS: All bladders were highly compliant over the volumes instilled (before sedation) with a maximum pressure during the filling phase of 0.9 cmH2O and a compliance of 943 mL/cmH2O. After sedation with propofol, the maximum pressure during the filling phase increased to 14 cmH2O with a compliance of 69 mL/cmH2O. Atropine antagonized this change in compliance; after sedation and atropine, the maximum pressure during the filling phase decreased to 4 cmH2O (P < 0.05) and the compliance increased to 337 mL/cmH2O (P < 0.05). CONCLUSION: The decrease in compliance seen in the pig bladder after sedation with propofol is mediated via muscarinic excitation. This probably occurs as a result of low-level tonic release of acetylcholine by the efferent parasympathetic nerves. The existence of such efferent excitatory activity during the storage phase in the overactive human bladder might explain the efficacy of bladder-selective muscarinic antagonists in a proportion of patients with detrusor hyper-reflexia and instability.

The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder.

OBJECTIVE: To investigate the effect of partial bladder outlet obstruction on detrusor blood flow and oxygen tension (PdetO2) in female pigs. MATERIALS AND METHODS: Detrusor-layer oxygen tension and blood flow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in five female Large White pigs with a partial urethral obstruction and in five sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described. RESULTS: In the obstructed bladders, blood flow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood flow declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals. CONCLUSION: In pigs with chronic bladder outlet obstruction, blood flow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during filling caused significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.

Studies of the pathophysiology of idiopathic detrusor instability: the physiological properties of the detrusor smooth muscle and its pattern of innervation.

PURPOSE: Idiopathic detrusor instability (IDI) is a common cause of lower urinary tract storage symptoms, such as urgency, frequency and urge incontinence. We have investigated the in vitro properties and pattern of innervation of the detrusor from patients with this condition. MATERIALS AND METHODS: Full thickness bladder specimens were obtained perioperatively from 14 patients with IDI and from 14 cadaveric controls undergoing transplant organ retrieval. Isolated detrusor smooth muscle strips were mounted in organ baths for isometric tension recording. Frequency-response curves to electrical field stimulation (EFS) (1 Hz to 50 Hz) and concentration response curves for carbachol (10(-7) M to 5 x 10(-4) M) and potassium (12 mM to 120 mM) were constructed. Acetylcholinesterase histochemistry and immunohistochemistry for both phosphorylated and non-phosphorylated neurofilaments was carried out on frozen sections of control and IDI bladders. RESULTS: IDI strips developed greater spontaneous tone (0.25 gm./mg. versus 0.12 gm./mg.; p <0.0001) and more spontaneous fused tetanic contractions (16.8% versus 6.8%; p <0.005) during an initial 90 minutes equilibration period. The IDI strips were less responsive than controls to nerve stimulation (max. response to EFS 0.79 gm./mg. versus 1.23 gm./mg.; p <0.0001) and were supersensitive to potassium (EC50 39.7 mM versus 45.7 mM; p = 0.003) but not to carbachol (EC50 7.3 x 10(-6) M versus 6.6 x 10(-6) M; p = 0.48). Morphometric studies revealed reduced staining of presumed cholinergic nerves, with 34.7% of IDI smooth muscle bundles appearing denervated compared with 1.5% of controls (p <0.0001). CONCLUSIONS: Our study supports the notion that there is a fundamental abnormality in IDI at the level of the bladder wall, with evidence of altered spontaneous contractile activity consistent with an increased electrical coupling of cells, a patchy denervation of the detrusor and a potassium supersensitivity.

Blood supply to the bladder during filling.

Amongst other features of bladder physiology, the mechanics of cyclic filling and emptying make the blood supply of the bladder unique with respect to other organs of the body. Blood vessels are required to lengthen and shorten, whilst maintaining sufficient perfusion of the smooth muscle. Interruption of the blood supply may result in ischaemia and, ultimately reperfusion, resulting in bladder pathologies. The blood flow is also likely to be affected by factors such as increased intra-abdominal pressure. In this article, several features of the blood supply to the bladder- and also the urethra--are discussed.

The in vivo and in vitro effects of hypoxia on pig urethral smooth muscle.

OBJECTIVE: To assess the in vitro effects of hypoxia on urethral smooth muscle and the role that these may have in the fall in urethral luminal pressure consequent upon interruption of its arterial blood supply. MATERIALS AND METHODS: In eight anaesthetized female Large White pigs, femoral blood pressure, urethral luminal pressure and lamina propria blood flow were recorded before, during and after aortic occlusion. In three animals, changes in urethral intramural oxygen tension were also recorded. Smooth muscle strips taken from the mid-urethra were studied in an organ bath under normal and hypoxic conditions, and in the presence of cyanide. The generation of spontaneous tone and the response to electrical-field stimulation were also examined. RESULTS: Urethral luminal pressure declined biphasically after aortic occlusion, from a mean of 83.8 to 39.0 cmH2O. The initial rapid phase seemed to be related to a decrease in urethral lamina propria blood flow, whilst the slower phase appeared to mirror the observed decline in intramural oxygen tension. In vitro, the high spontaneous tone of the muscle strips was abolished by hypoxia or metabolic inhibition whilst the contractile response to nerve stimulation was preserved. CONCLUSIONS: The decrease in urethral pressure after aortic occlusion appears to have two components, the first mediated through a decrease in vascular filling of the lamina propria and the second as a result of hypoxia-induced smooth muscle relaxation. The in vitro effects of hypoxia upon urethral smooth muscle concur with the changes observed in vivo.

Urinary bladder blood flow changes during the micturition cycle in a conscious pig model.

PURPOSE: To develop a method using laser Doppler flowmetry in conscious pigs, which allows the accurate simultaneous measurement of cystometric and cardiovascular parameters together with changes in vesical blood flow. The animal model was then used to investigate the changes in blood flow in the urinary bladder which occur during the micturition cycle. MATERIALS AND METHODS: Seven large white female pigs were subjected to chronically implanted vascular access and urodynamic catheters as well as an intramural vesical laser Doppler probe. The animals underwent repeated conscious urodynamics with simultaneous measurement of cardiovascular, urodynamic and vesical blood flow parameters. RESULTS: The model shows both compliant and low-compliance behavior and allows greater investigation of the effects of intravesical pressure on blood flow. Blood flow is not altered, during compliant filling and voiding transiently decreases flow to 38% of resting levels, with a rapid return to normal. Low-compliance filling results in a progressive fall in blood flow to a minimum of 45% of normal. At all times an inverse relationship between intravesical pressure and blood flow is maintained. CONCLUSIONS: The pig model proved to be well suited to the experimental conditions and provided reproducible results. The principal determinant of blood flow within the wall of the bladder is the pressure within its lumen. During normal filling the blood supply of the bladder is able to adapt to the large increase in surface area which occurs, maintaining blood flow until the pressure increases.

Intrinsic urethral closure mechanisms in the female pig.

This study investigates the role of the various components of the female pig urethral wall in the generation of the urethral closure pressure. Prior to voiding urethral pressure fails and this is accompanied by a rise in lamina propria blood flow. Pharmacological manipulation shows that striated muscle is not involved in the generation of the urethral closure pressure. Drugs active upon smooth muscle change urethral pressure significantly by a mechanism independent of their cardiovascular system effects. Histological studies show that it is possible to correlate the disposition of circular smooth muscle with the urethral pressure profile. In vitro smooth muscle from the high pressure zone is pharmacologically different to that from the proximal urethra in a manner which may reflect their physiological roles.

Familial transitional cell carcinoma and the Lynch syndrome II.

A family is presented in which 4 male siblings developed transitional cell carcinoma (TCC). Four upper tract tumours occurred in 3 and in the fourth the tumour was intravesical. Two of these patients also had colorectal adenocarcinoma. There were 2 other relatives in the pedigree with large bowel cancer. It is suggested that this is an example of Lynch Syndrome II, a hereditary non-polyposis colorectal cancer with extracolonic cancer sites. The implications regarding the screening, surveillance and detection of possible carrier status in healthy relatives is discussed.

Optical urethrotomy under local urethral anaesthesia.

A series of 46 patients underwent 76 optical urethrotomies under local urethral anaesthesia in the out-patient clinic; in 70% of patients the strictures were controlled by local anaesthetic urethrotomy alone; 61% felt either no pain or mild pain during the procedure; 72% expressed a preference for local anaesthesia should the procedure have to be repeated and 82% were happy with the result of their treatment. Optical urethrotomy under local urethral anaesthesia produces results comparable to those reported by others using general anaesthesia. If large numbers of patients are to be treated, possibly repeatedly, then out-patient urethrotomy may result in more efficient use of resources.