CYSTOMETRIC EVALUATION OF BLADDER FUNCTION IN NON-ANESTHETIZED MICE WITH AND WITHOUT BLADDER OUTLET OBSTRUCTION

 

Authors:

R K Pandita, M Fujiwara, H Mizusawa, P Alm* and K-E Andersson

   

Institution:

Department of Clinical Pharmacology and *Pathology, Lund University Hospital, Lund, Sweden

     

Conference:

ICS 2000 Tampere

       

Type:

Podium Session

         

Category:

Neurophysiology and Basic Science

                 

Aims of Study
Transgenic knockout mice may be a useful tool for examination of the molecular mechanisms underlying various forms of bladder dysfunction. There are several published reports on cystrometry in mice both without and with bladder outlet obstruction (1-4). However, these investigations have been performed in anesthetized animals, which precludes information on active micturition. Development of a reliable and reproducible cystometric model in the non-anesthetized mouse is desirable. The aim of the present study was to develop a model for cystrometric study of bladder function in the awake mouse, and to characterize urodynamically and immunohistochemically the normal and infravesically obstructed mouse bladder.

Methods
Normal Balb/CJ mice, and mice with bladder outlet obstruction after surgical, partial ligation of the urethra underwent continuous cystometry as previously described for rats (5). Bladders were also investigated by immunohistochemistry.

Results
During the period of cystometry, reproducible micturition patterns were obtained. Bladder overactivity could be evoked by intravesical administration of capsaicin and prostaglandin E2, and by subcutaneous apomorphine. Marked differences in the urodynamic parameters between normal and obstructed mice were revealed. In mice subjected to urethral obstruction, micturition pressure (p<0.05), threshold pressure (p<0.05), bladder capacity (p<0.001), micturition volume (p<0.001), and residual volume (p<0.05) increased significantly. There was no difference in basal pressure or compliance between normal and obstructed mice. Non-voiding bladder activity was consistently recorded in obstructed mice; both frequency and amplitude increased significantly (p<0.01). Compared to normal bladders, obstructed bladders showed hypertrophy of the bladder wall and various degrees of ěpatchy denervationî of the detrusor.

Conclusions
Continuous cystometry can be reproducibly performed in awake, freely moving normal mice and mice with bladder outflow obstruction. The changes induced by infravesical obstruction in mice were similar to those previously found in rats. This model may be useful for investigations of genetically modified mice.

References
(1) J. Urol., 141: 1245, 1989
(2) J. Urol., 148: 183, 1992
(3) J. Urol., 157: 1109, 1997
(4) J. Urol., 161: 1015, 1999
(5) J. Urol., 137: 1291, 1987