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439: Detrusor underactivity (DU) caused by bladder outlet obstruction (BOO) is associated with an early impairment of the bladder sensory mechanism

Speaker
L. Vale, Vizela (PT)
Authors
Vale L. 1 , Antunes-Lopes T. 1 , Avelino A. 1 , Birder L.A. 2 , Charrua A. 1 , Cruz F. 1
Institutions
1Hospital Sao João & Faculty of Medicine/i3S of Porto, Dept. of Urology, Porto, Portugal, 2University of Pittsburgh, Dept. of Pharmacology, Pittsburgh, United States of America, 3
Event
33rd Annual EAU Congress Copenhagen
Date – time - Location
18 March 2018, 12:15 - 13:45, Green Area, Room 1 (Level 0)
Session
Poster Session 33 - Better understanding LUTS: A look behind the curtain
Topic
Functional LUTS, incontinence and neuro-urology: Basic science

Introduction & Objectives

DU is a contraction of reduced strength and/or duration, resulting in prolonged or incomplete bladder emptying. Estimates suggest that DU prevalence ranges from 9-23% in men 70y. DU is therefore expected to be a common complication of BOO. Here, we test the hypothesis that DU occurring after BOO results from an early impairment of the bladder afferent signalling mechanism.

Materials & Methods

BOO was obtained by creating partial urethral obstruction in female rats. After 3 and 15 days, rats were anaesthetised and cystometries were performed using saline infusion for 30 minutes at 6 ml/hour. DU and elevated voiding contractions (contr) were defined as the average contr of naïve animals ± 4 sd. This defined the cut-off at 1 contr/min, respectively. Saline voided was stored for ATP measurement DU bladders were then submitted to (i) intravesical infusion of 5 mg/kg ATP and (ii) serosal application of Ach (1 µM) or ATP 5 mg/kg. Sham-operated animals were used as controls. ATP was measured by bioluminescence using firefly luciferase at 37°C.

Results

Control rats had 0.6±0.1 voiding cont/min. At 3 days after BOO, 63% (5/8) of rats had 1.4±0.4 contr/min, p<0.01) while 29% (2/8) had normal frequency (0.7±0.1 voiding contr/min) and 13% (1/8) had DU (0.0±0.0 voiding contr/min, voiding by overflow).
At 15 days, 67% (6/9) of rats had DU (0.1±0.1 voiding contr/min, p<0.01, most of urine voided by overflow), while the remaining 33% (3/9) had more voiding contractions than controls (1.2±0.3 cont/min, p<0.05).
ATP in saline voided was 1.08E-14 mol/ml in control rats. ATP was significantly higher (1.08E-12 mol ATP/ml, p<0.01) in rats with more voiding contractions and was significantly lower (4.18E-17 mol ATP/ml, p<0.001) in rats with DU (see Fig).
In DU bladders, serosal application of Ach or ATP generated immediate expulsive detrusor contractions (12 cmH20 and 17 cmH20, respectively), indicating the integrity of the detrusor muscle. Intravesical application of ATP generated immediate expulsive detrusor contractions of 46 cmH20, denoting a low availability of urothelial ATP.
Image

Conclusions

This study suggests that BOO impairs the afferent pathway before impairing the detrusor, with urothelial ATP being less available to promote bladder contraction. This mechanism may open new therapeutic options to overcome DU after BOO.