Hypothesis / aims of study
Rodents have served to study the function of the lower urinary tract for many years. Mice models are leading in genetic research and widely used in urodynamic studies. Compared to humans animal research is less controlled by standards which leads to a wide heterogeneity and poor comparability of studies. The aim of this review was to provide an overview of the prevailing situation of urodynamic studies in mice, to conduct a quality assessment and to define normative values for urodynamic studies in mice.
Study design, materials and methods
A systematic search was conducted on EMBASE, MEDLINE, SCOPUS and PubMed database. The focus was set on studies performing cystometries using in vivo mice. The existence of a control group and publication of analysable data were amongst others some of the requirements. In addition to outcome values, information on experimental setup as well as mice characteristics were extracted. The quality assessment was carried out based on the SYRCLE Bias Risk Tool for Animal Studies.
Results
In the first phase 2718 publications were identified, out of which 162 reported on urodynamic studies in mice. An increasing prevalence of urodynamic studies over the years can be observed. Based on our inclusion and exclusion criteria 86 studies were extracted for the final review. The analysis of the included studies revealed 18 different mouse strains from 5 to 104 weeks old with a weight range from 13.4 gram to 61 gram, ten different anaesthetics and their combinations in varying doses as well as infusion speeds differing between 0,59 and 80 μl/min. Saline was the most widely used infusion liquid (82.6%). The distribution of cystometries carried out in anaesthetised (47.7%) and awake mice (55.8%) was nearly the same with some studies undertaking the measurement both ways. Three different types of bladder catheterisation (implanted catheter, transvesical cannulation and transurethral catheter) were used and cystometry was carried out between 0 and 8 days after catheter implantation. The duration of the measurements varied between 20 to 150 minutes. Furthermore there was no consistency of terminology. A number of synonyms were used in the literature but also varying definitions of identical terms occured. The quality assessment disclosed a medium to high risk of bias in the included publications. Randomised group assignment as well as blinding of personnel and outcome assessment were implemented only in three to seven studies. Apart from the variety of study and animal characteristics the reporting rate of the analysed factors was low. Overall, the average reporting rate per urodynamic influencing factor was 69,9%.
Interpretation of results
Due to the lack of guidelines on rodent urodynamic studies, a vast heterogeneity of methods and cystometry setups were discovered. This is crucial as all these factors have been described as relevant confounders of urodynamic studies. We identified incomplete and undetailed reporting being a general problem. All publications lacked information on key aspects of study and experimental setups. The combination of incomplete reporting and heterogeneity of studies prevent a meaningful analysis and identification of normative values as for each calculation the constellation of the different modifiers (age, sex and strain of mouse, type of catheter, infusion liquid and speed etc.) has to be considered. Thus, no meta-analysis could be conducted. Instead results are made publicly accessible through a website currently under construction.