Submitted on November 8, 2004
Accepted on January 7, 2005
New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency
Larissa V Rodriguez1*, Shinhong Chen1, Gregory S Jack1, Fernando de Almeida1, Kyo Won Lee1, and Rong Zhang1
1 Urology, The Geffen School of Medicine at UCLA, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: lrodriguez{at}mednet.ucla.edu.
Existing animal models of stress urinary incontinence (SUI) are limited due to the low rate of incontinence seen in the animals and to their relatively low durability. In addition, most methods described to measure incontinence are operator dependent. The aim of this study was to develop a new durable animal model of SUI and establish objective measures to quantify SUI. We subjected female rats to transabdominal urethrolysis. At baseline and at 1, 4, 8, 12 and 24 weeks after intervention animals underwent cystometry and evaluation with abdominal leak point pressure (ALLP). Urethral resistance was evaluated by retrograde urethral perfusion pressure (RUPP). Tissues were obtained for histology and immunohistochemistry. Normal female rats had an average ALPP of 19.4 cmH2O and RUPP of 22.6 cmH2O at baseline. More than 93% of the animals had significantly decreased ALPP and RUPP after the procedure. The mean ALPP and RUPP decreased to 9.8 cmH2O and 11.2 cmH2O respectively by one week after urethrolysis. These changes were maintained for up to 24 weeks. Changes seen in urethral resistance and ALPP appear to be mediated by apoptosis, decreased neuronal mass, and smooth muscle atrophy. These results indicate that transabdominal urethrolysis is a reliable method of achieving durable decreased urethral resistance in a SUI model. RUPP and ALPP are objective and reproducible methods of assessing urethral resistance. Changes in continence and urethral resistance appear to be mediated by denervation and smooth muscle atrophy, which are seen in both elderly incontinent patients and in patients with intrinsic sphincter dysfunction.
