Persistently Increased Voiding Frequency Despite Relief of Bladder Outlet Obstruction

Chai, Toby C.; Gemalmaz, Hakan; Andersson, Karl‐Erik; Tuttle, Jeremy B.; Steers, William D.

doi:10.1016/s0022-5347(05)69006-4

Cited by 52 publications

(14 citation statements)

References 18 publications

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“…Interest in the structures of this region is increasing following the realization that damage might contribute to changes resulting in general pathology, specifically overactive bladder [4,6–8]. Several structures are obvious candidates for such damage (nerve trunks, superficial and intramural ganglia and blood vessels).…”

Section: Discussionmentioning

confidence: 99%

“…Damage to the bladder neck is associated with increased voiding frequency, an increase in bladder excitability, and major changes to the thickness of the bladder wall and its cellular constituents [1–7]. Typically, these changes result from ligatures or restrictions applied to the urethra that are put in place to reduce urine flow, an approach designed to mimic BOO caused by conditions such as BPH [1,3].…”

Section: Introductionmentioning

confidence: 99%

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Regional differences in sensory innervation and suburothelial interstitial cells in the bladder neck and urethra

et al. 2008

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OBJECTIVE To identify and characterize possible structural specialisations in the wall of the lower urinary tract (LUT) in the region of the bladder urethral junction (BUJ), with the specific objective of identifying regional variations in sensory nerve fibres and interstitial cells (ICs). MATERIALS AND METHODS The bladder base and urethra was removed from five male guinea pigs killed by cervical dislocation. Tissue pieces were incubated in Krebs’ solution at 36 °C, gassed with 95% O2 and 5% CO2, fixed in 4% paraformaldehyde and processed for immunohistochemistry. The nonspecific marker vimentin and the general neuronal marker protein gene product (PGP) 9.5 were used to identify ICs and nerve fibres, respectively. Specific antibody binding was visualized using the appropriate secondary antibodies. RESULTS The wall of the LUT in the region immediately between the bladder base and the urethra, the BUJ, differed in its cellular composition relative to the adjacent areas. PGP‐positive (PGP+) nerve fibres, presumptive afferent fibres, lay within the urothelium running between the epithelial cells. There were two general nerve patterns: branching fibres with no varicosities, and complex fibres with varicosities. Fibre collaterals with varicosities exited the urothelium and occupied the space under the urothelium adjacent to the layer of suburothelial ICs. The latter, lamina propria and around the muscle bundles were identified using vimentin (vim+). In the base a few vim+ cells were also PGP+. In the region of the BUJ there was a decrease in the amount of smooth muscle. In this region, below the lamina propria, there was an area densely populated with vim+/PGP+ ICs. Nerve fibres ran between the cells in this region. CONCLUSION These structural specialisations within the urothelium and deeper layers of the BUJ suggest that they might be associated with specific functions. The localized highly branched network of the putative afferent nerves suggests the presence of a local axonal reflexes involving possible cross‐talk between the urothelium and suburothelial layer. The function of the specialized region of ICs is not known and must await further information on the functional properties of this novel cell type. These observations show further the cellular heterogeneity of the cells in the LUT and the complexity of the structures. One of the major current challenges in functional urology is to understand the relationships between these novel structures and overall bladder and urethral function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regional differences in sensory innervation and suburothelial interstitial cells in the bladder neck and urethra

et al. 2008

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“…Increases in connective tissue between muscle fibers and between muscle bundles significantly decrease bladder elasticity, resulting in a decrease in compliance. Reversal of partial obstruction of the animal bladder outlet, in most cases, results in a progressive decrease in bladder mass, increased compliance, and improved contractile responses to all forms of stimulation tested [Malgren et al, 1990;Malqvist et al, 1991;Gabella et al, 1992;Seki et al, 1992b;Wang et al, 1995;Chai et al, 1999]. When decompensation progresses beyond some critical point, however, removing the obstruction does not improve bladder function, and bladder dysfunction proceeds to end-stage decompensation.…”

Section: Compliancementioning

confidence: 99%

Obstructive response of human bladder to BPH vs. rabbit bladder response to partial outlet obstruction: A direct comparison

et al. 2000

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“…Indeed, the clinically relevant period available to treat and study this condition is during the post‐release phase, once the anatomic obstruction itself has been detected and mitigated. While several reports have described the effect of REL, the response to targeted pharmacotherapy in the REL period has not systematically combined molecular and functional analyses to find novel relevant candidates. While some molecular studies have looked at early genome‐wide responses after a 10‐days of REL, this timepoint may still be a part of the healing phase post‐release.…”

Section: Introductionmentioning

confidence: 99%

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin

et al. 2020

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Current and potential medical therapy for obstruction‐induced myopathic bladder dysfunction (from benign prostatic hyperplasia or posterior urethral valves) focuses on symptoms. The persistent tissue pathology and dysfunction after release of obstruction is often deemed irreversible without any systematic therapeutic approaches. As rapamycin can attenuate bladder smooth muscle hypertrophy and dysfunction during the genesis of partial obstruction in vivo, we tested whether rapamycin could improve persistent function after release of obstruction (de‐obstruction or REL). Female Sprague‐Dawley rat bladders were partially obstructed (PBO) by suturing around both the urethra and a para‐urethral steel rod, then removing the rod. One day prior to release of obstruction (preREL), voiding parameters and residual urine volume of preREL+future rapa, preREL+future veh groups were recorded. Release of obstruction (REL) was performed by suture removal following 6 weeks of PBO. For 4 more weeks after the de‐obstruction, REL animals were randomized to rapamycin (REL+rapa) or vehicle (REL+veh). PBO for 6 weeks were used as positive controls. In shams, the urethra was exposed, but no suture tied. Voiding parameters and residual urine volume were measured prior to sacrifice of sham and REL+veh or REL+rapa, and PBO. Rapamycin efficacy was tested by pair‐wise comparison of changes in individual voiding data from preREL+future veh or preREL+future rapa versus REL+veh or REL+rapa, respectively, as well as by comparisons of REL+veh to REL+rapa groups. Bladders were weighed and processed for a high‐throughput QPCR array, and histopathology. Bladder/body mass ratios with PBO increased significantly and remained higher in the release phase in REL+veh animals. REL+rapa versus REL+veh improved residual volumes and micturition fractions toward sham levels. Three genes encoding extracellular proteins, BMP2, SOD3, and IGFBP7, correlated with functional improvement by Pearson's correlations. The promoters of these genes showed enrichment for several motifs including circadian E‐boxes. While obstruction and REL augmented CLOCK and NPAS2 expression above sham levels, rapamycin treatment during release significantly blocked their expression. This experimental design of pharmaco‐intervention during the de‐obstruction phase revealed a novel pathway dysregulated during the clinically relevant treatment phase of obstructive bladder myopathy.

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Persistently Increased Voiding Frequency Despite Relief of Bladder Outlet Obstruction

Cited by 52 publications

References 18 publications

Regional differences in sensory innervation and suburothelial interstitial cells in the bladder neck and urethra

Regional differences in sensory innervation and suburothelial interstitial cells in the bladder neck and urethra

Obstructive response of human bladder to BPH vs. rabbit bladder response to partial outlet obstruction: A direct comparison

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin

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