Effects of opioids and benzodiazepines on bladder function of awake restrained mice.

von Siebenthal, Michelle; Schneider, Marc P.; Zheng, Shaokai; Wüthrich, Patrick Y.; Burkhard, Fiona C.; Monastyrskaya, Katia (2021). Effects of opioids and benzodiazepines on bladder function of awake restrained mice. American journal of clinical and experimental urology, 9(6), pp. 456-468. e-Century Publishing

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OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy
10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research > ARTORG Center - Cardiovascular Engineering (CVE)

UniBE Contributor:

von Siebenthal, Michelle Andrea, Schneider, Marc Philipp, Zheng, Shaokai, Burkhard, Fiona Christine, Monastyrskaya-Stäuber, Katia

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2330-1910

Publisher:

e-Century Publishing

Language:

English

Submitter:

Jeannie Wurz

Date Deposited:

18 Jan 2022 16:19

Last Modified:

05 Dec 2022 16:03

PubMed ID:

34993265

Uncontrolled Keywords:

Urodynamic investigation (UDI) awake mice electromyography (EMG) external urethral sphincter (EUS) fentanyl hydromorphine midazolam

BORIS DOI:

10.48350/164334

URI:

https://boris.unibe.ch/id/eprint/164334

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