A canine model of irreversible urethral sphincter insufficiency.
OBJECTIVE
To develop a canine model of external urinary sphincter insufficiency by creating irreversible damage to the sphincter, because there is a need for a reliable and reproducible large animal model for the study of stress urinary incontinence (SUI) caused by deficient sphincter function.


METHODS
About a quarter of the total external sphincter muscle was removed microsurgically from seven female dogs; three age-matched dogs served as normal controls. The dogs had standard urodynamic and radiographic studies before and at 1, 2, 3, 4 and 7 months after surgery. Three dogs were killed at 4 months and four at 7 months after surgery for tissue analyses.


RESULTS
The interventions produced a consistent outcome. Urodynamic studies showed a significant and sustained decrease in sphincter function, which included a static urethral pressure profile, stress urethral profile and detrusor leak-point pressure. Furthermore, in vivo pudendal nerve stimulation and organ-bath studies of the retrieved tissue strips confirmed the loss of sphincter tissue function. Histologically, absence of functional sphincter muscle was evident in the damaged sphincter region.


CONCLUSIONS
These results show that a reliable and reproducible canine model of irreversible sphincter insufficiency can be created by microsurgical removal of sphincter muscle tissue. This model of external sphincter insufficiency could be used for evaluating methods (e.g. cell therapies) for treating SUI.
Eberli
Daniel
D
Wake Forest Institute for Regenerative Medicine, Medical Center Boulevard, Winston-Salem, NC 27514-1094, USA.
Andersson
Karl-Erik
KE
Yoo
James J
JJ
Atala
Anthony
A
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D009119:Muscle Contraction; D014521:Urethra / Q000293:injuries*; D014550:Urinary Incontinence, Stress / Q000209:etiology* / Q000503:physiopathology; D014563:Urodynamics