MP60-19 MUSCARINIC INDUCED BLADDER CONTRACTILITY IS ALTERED IN AN ANIMAL MODEL FOR NEUROGENIC DETRUSOR UNDERACTIVITY

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2016MP60-19 MUSCARINIC INDUCED BLADDER CONTRACTILITY IS ALTERED IN AN ANIMAL MODEL FOR NEUROGENIC DETRUSOR UNDERACTIVITY Karel Dewulf, Emmanuel Weyne, Yves Deruyver, Rieta Van Bree, Dirk De Ridder, Maarten Albersen, and Wouter Everaerts Karel DewulfKarel Dewulf More articles by this author , Emmanuel WeyneEmmanuel Weyne More articles by this author , Yves DeruyverYves Deruyver More articles by this author , Rieta Van BreeRieta Van Bree More articles by this author , Dirk De RidderDirk De Ridder More articles by this author , Maarten AlbersenMaarten Albersen More articles by this author , and Wouter EveraertsWouter Everaerts More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.872AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pelvic surgery induced detrusor underactivity (DU) is a poorly understood condition. Recent studies have shown increased muscarinic M2 receptor (M2) at protein levels in multiple animal models of DU. We aim to establish a regenerative animal model mimicking iatrogenic neurogenic DU and evaluate muscarinic bladder control in our DU animal model. METHODS Male Sprague-Dawley rats underwent preganglionic pelvic nerve crush injury (PNI, 3x15s) or sham surgery. Sequential urine spotting tests and 24 hours urine collections were planned at 1, 3 and 9 weeks following PNI to assess regeneration of bladder function. We evaluated bladder function in vivo by awake cystometry. After cystometry, full thickness bladder wall strips were taken for in vitro organ bath studies. Contractile responses to cumulative doses of arecaidine but-2-ynyl ester tosylate (ABET, a preferential M2-agonist, 10-9-3x10-4 M) and carbachol (a non-selective muscarinic agonist, 10-8-10-4 M) were recorded. Changes in gene expression of vesicular acetylcholine transporter (VAchT), M2 and M3 muscarinic receptors (M3) were assessed at 1 week (sham and PNI) and 9 weeks (PNI) by RT-qPCR. RESULTS A higher number of spots was seen one week after PNI (p<0,001) compared to all other time points. Mean area of spots was more then halved at all time points compared to sham surgery (p<0,0001). In contrast to regular micturition cycles seen in sham animals on awake cystometry, animals showed overflow incontinence one week following PNI and partial recovery at 3 and 9 weeks. Maximum pressure was halved and the intercontractile interval was higher at 3 and 9 weeks (respectively p<0,0001 and p<0,05) and the voided volume was tripled at 3 weeks (p<0,01). Maximum responses to ABET were higher 1 week after PNI (p<0,05) and the EC50 was reduced at 1 and 3 weeks (p<0,001). Maximum responses to carbachol were reduced at 3 and 9 weeks (p<0,001) and the EC50 was reduced at 1 and 3 weeks following PNI (p<0,05), all compared to sham surgery. No differences were seen in the gene expression of M2 and M3 muscarinic receptors. Relative expression of VAchT was reduced 9 weeks following PNI (p<0,05). CONCLUSIONS We established a rat animal model to study functional bladder regeneration in neurogenic DU by crushing the preganglionic pelvic nerve. Muscarinic induced bladder contractility is reduced at 3 and 9 weeks following PNI, although it is initially compensated by M2 upregulation and/or sensitization. This could explain the failure of parasympathomimetics and acetylcholine-esterase inhibitors in the treatment of DU. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e801-e802 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Karel Dewulf More articles by this author Emmanuel Weyne More articles by this author Yves Deruyver More articles by this author Rieta Van Bree More articles by this author Dirk De Ridder More articles by this author Maarten Albersen More articles by this author Wouter Everaerts More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...