PD36-03 EARLY FESOTERODINE FUMARATE ADMINISTRATION PREVENTS THE ONSET OF NEUROGENIC DETRUSOR OVERACTIVITY AFTER SPINALIZATION IN RATS

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II1 Apr 2018PD36-03 EARLY FESOTERODINE FUMARATE ADMINISTRATION PREVENTS THE ONSET OF NEUROGENIC DETRUSOR OVERACTIVITY AFTER SPINALIZATION IN RATS Mikolaj Przydacz, George Loutochin, Phillippe Cammisotto, Jakub Zimoch, Naciba Benlimame, Lysanne Campeau, and Jacques Corcos Mikolaj PrzydaczMikolaj Przydacz More articles by this author , George LoutochinGeorge Loutochin More articles by this author , Phillippe CammisottoPhillippe Cammisotto More articles by this author , Jakub ZimochJakub Zimoch More articles by this author , Naciba BenlimameNaciba Benlimame More articles by this author , Lysanne CampeauLysanne Campeau More articles by this author , and Jacques CorcosJacques Corcos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1726AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Onset of detrusor overactivity (DO) after spinal cord injury (SCI) affects patient′s quality of life and renal function. Electrical neuromodulation implemented immediately after injury in patients after SCI is currently the only recognized approach preventing DO. The aim of this experiment was to assess the urodynamic efficacy of early fesoterodine fumarate (FF) administration in preventing DO in a spinal cord transected (SCT) rat model and investigate whether observed effects were due to alternations in expression patterns of bladder muscarinic receptors. METHODS 33 Sprague-Dawley rats were allocated to 6 groups - Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10 and FF was continuously administered from post-op day 1. Cystometry was undertaken 6 weeks after SCT in awaked rats right before the animals were sacrificed. Changes of bladders layers were assessed by hematoxylin/eosin and Masson′s trichrome staining. Distribution of the receptors was investigated by immunofluorescence staining against muscarinic receptors (M1 to M5) and their prevalence was analyzed by Western blots. Comparisons were conducted using Kruskall-Wallis test (post-hoc Dunn test). RESULTS Urodynamic data: 6 weeks after SCT, intermicturition pressure was lower in low dose treated group (Group 4) compared to SCT controls (p<0.05) whereas maximum pressure was lower in most of the SCT treated rats (Groups 3-5) (p<0.01). Threshold pressure was lower in full time treated rats (Group 3-4) (p<0.05). Morphological data: No changes were noticed within the bladders layers in terms of degree of fibrosis and muscle hypertrophy. Expression of M2 receptors was lower in groups with wash-out period (Groups 5 and 6) (p<0.01) whereas expression of M3 receptors was higher in Groups 4 and 5 (p<0.01). CONCLUSIONS Early FF administration in a SCT rat model prevents the onset of DO and modifies profile of bladder muscarinic receptors. The treatment effect is sustained after a washout period. The evidence is strong enough to support clinical trials analyzing long-term prevention of DO in patients after SCI with the presented approach. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e727 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Mikolaj Przydacz More articles by this author George Loutochin More articles by this author Phillippe Cammisotto More articles by this author Jakub Zimoch More articles by this author Naciba Benlimame More articles by this author Lysanne Campeau More articles by this author Jacques Corcos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...