von Siebenthal Michelle, Schneider Marc P, Zheng Shaokai, Wuethrich Patrick Y, Burkhard Fiona C, Monastyrskaya Katia
Urology Research Laboratory, Department for BioMedical Research DBMR, University of Bern Switzerland.
Urogenital Engineering Group, ARTORG Center, Faculty of Medicine, University of Bern Bern, Switzerland.
Am J Clin Exp Urol. 2021 Dec 15;9(6):456-468. eCollection 2021.
We aimed to study the effects of anaesthetics on bladder function using repeated urodynamic investigation (UDI) including external urethral sphincter (EUS) electromyography (EMG) in awake restrained mice.
Female C57Bl/6J mice underwent either bladder catheter (n=6) or bladder catheter plus electrodes (n=10) implantation next to the EUS. A control group (n=3) was included for histological analysis. Following awake UDI, the effects of midazolam (5 mg/kg) and opioids (fentanyl (50 μg/kg) and hydromorphine (250 μg/kg)) on bladder function were studied. Mice were allowed to recover from drug application for at least one day before being subjected to the next drug and UDI. Bladder weight was assessed and fibrotic changes were analysed by Masson's trichrome staining.
EUS-EMG activity during voiding was reduced compared to before and after voiding in baseline measurements. Threshold and maximal detrusor pressure were significantly increased in both midazolam and the opioids. The opioids lead to either a significantly increased bladder filling volume and micturition cycle duration (hydromorphine) or a complete loss of the voiding phase leading to overflow incontinence (fentanyl). Bladder-to bodyweight ratio was significantly increased in both groups with an implanted catheter compared to controls. No differences were observed between the groups with- or without implanted electrodes regarding bladder-to bodyweight ratio, bladder fibrosis and urodynamic parameters.
Repeated UDIs combined with EUS-EMG are feasible in the awake mouse model. The presence of electrodes next to the EUS does not obstruct the bladder outlet. Opioids and benzodiazepines severely interfere with physiological bladder function: fentanyl and hydromorphine disrupted the voiding phase evidenced by the reduced coordination of EUS activity with detrusor contraction, while bladder emptying under midazolam was achieved by EUS relaxation only.
我们旨在通过重复尿动力学检查（UDI），包括在清醒受限小鼠中进行尿道外括约肌（EUS）肌电图（EMG）检查，研究麻醉剂对膀胱功能的影响。
雌性C57Bl/6J小鼠在EUS旁植入膀胱导管（n = 6）或膀胱导管加电极（n = 10）。设立一个对照组（n = 3）用于组织学分析。在清醒状态下进行UDI后，研究咪达唑仑（5 mg/kg）和阿片类药物（芬太尼（50 μg/kg）和氢吗啡酮（250 μg/kg））对膀胱功能的影响。在给予下一种药物和进行UDI之前，让小鼠从药物作用中恢复至少一天。评估膀胱重量，并通过Masson三色染色分析纤维化变化。
在基线测量中，排尿期间的EUS - EMG活动与排尿前和排尿后相比有所降低。咪达唑仑和阿片类药物组的阈值和最大逼尿肌压力均显著升高。阿片类药物导致膀胱充盈量和排尿周期持续时间显著增加（氢吗啡酮），或导致排尿期完全丧失，进而导致充溢性尿失禁（芬太尼）。与对照组相比，两个植入导管组的膀胱与体重之比均显著增加。在膀胱与体重之比、膀胱纤维化和尿动力学参数方面，植入电极组和未植入电极组之间未观察到差异。
在清醒小鼠模型中，重复进行UDI并结合EUS - EMG是可行的。EUS旁电极的存在不会阻塞膀胱出口。阿片类药物和苯二氮䓬类药物严重干扰膀胱生理功能：芬太尼和氢吗啡酮破坏排尿期，表现为EUS活动与逼尿肌收缩的协调性降低，而咪达唑仑作用下膀胱排空仅通过EUS松弛实现。
