Lori Birder led the peer-review process as the Associate Editor responsible for the paper.
Urodynamic improvements following oral medical therapy for partial bladder outlet obstruction in an animal model
Article first published online: 26 NOV 2013
© 2013 Wiley Periodicals, Inc.
Neurourology and Urodynamics
Volume 34, Issue 3, pages 286–291, March 2015
How to Cite
Maciejewski, C. C., Tredget, E. E. and Metcalfe, P. D. (2015), Urodynamic improvements following oral medical therapy for partial bladder outlet obstruction in an animal model. Neurourol. Urodyn., 34: 286–291. doi: 10.1002/nau.22528
Conflict of interest: none.
- Issue published online: 12 MAR 2015
- Article first published online: 26 NOV 2013
- Manuscript Accepted: 22 OCT 2013
- Manuscript Received: 24 JUL 2013
- Northern Alberta Urologic Foundation
- Edmonton Firefighters Burn Treatment Society
- Stollery Children's Hospital Foundation
- Lilly Pharmaceutical
- partial bladder outlet obstruction, rapamycin, tadalafil
Bladder deterioration after partial outlet obstruction (pBOO) occurs commonly and has significant clinical implications. Our previous animal model results described the progression of pBOO to hypertrophy and fibrosis. We wished to determine if the pathologic process of pBOO can be altered with rationally chosen oral medications.
Materials and Methods
Female Sprague–Dawley rats underwent controlled surgically induced pBOO. Rats were maintained for a period of 16 weeks at which point urodynamics were performed, and organs harvested. Rats were divided into four groups, each receiving different daily treatment: control (saline), oxybutynin (3 mg/kg), rapamycin (2 mg/kg), and tadalafil (2 mg/kg). Outcomes were assessed after 4,8,12, or 16 weeks. Measures included animal health, urodynamics, histology, mass spectrometry for collagen content, and rtPCR for inflammatory mediators.
Rapamycin treated animals exhibited significant mortality at later time points. Oxybutinin and tadalafil treated bladders demonstrated significant improvements in bladder capacity and compliance, with less detrusor hypertrophy than controls. Tadalafil also resulted in a significant down-regulation of HIF-1α, while decorin, biglycan, and TGF-β were upregulated in treated animals. Tadalafil treated bladders measured lower collagen content towards the end of the study, indicating an antifibrotic effect.
Our study has effectively demonstrated that deleterious changes secondary to pBOO can be altered pharmacologically. Oxybutinin and tadalafil seem to have a time-dependent protective effect on the detrusor muscle, although with different mechanisms of action. Tadalafil treatment in this setting appears to have an antifibrotic effect. This work has the potential to seed important clinical studies and improve clinical practice. Neurourol. Urodynam. 34:286–291, 2015. © 2013 Wiley Periodicals, Inc.