title: A nonhuman primate model of stable urinary sphincter deficiency.
abstract: OBJECTIVE
  The pathophysiology of urinary sphincter deficiency in women remains incompletely understood and current treatment options have limitations. Female nonhuman primates may represent a relevant animal model for studies of pathophysiology and treatment interventions because of their human-like reproductive and age associated stages of life (premenopause, perimenopause and postmenopause), lower urinary tract structure and bipedal posture. We developed and characterized a nonhuman primate model of defined injury to the urethral sphincter complex.
  
  
  METHODS
  We used 22 adult female cynomolgus monkeys in which injury to the sphincter complex was created by cauterizing and then transecting its pudendal innervation. Urodynamic studies were performed before and during pudendal and hypogastric nerve stimulation at baseline, and 3, 6 and 12 months after injury. We also analyzed sphincter structure in vivo by cystourethrography, and ex vivo by quantitative histology and immunohistochemistry at these time points.
  
  
  RESULTS
  Injury produced a 47% to 50% decrease in maximal urethral pressure (vs baseline p <0.05). It also abolished the increase in maximal urethral pressure in response to pudendal and hypogastric nerve stimulation (vs baseline p >0.05), which persisted more than 12 months after injury. Urodynamic changes were consistent with decreased skeletal and smooth muscle content, decreased nerve responses and an associated decrease in somatic and adrenergic innervation in the sphincter complex.
  
  
  CONCLUSIONS
  These structural and urodynamic changes are consistent with those in patients with stress urinary incontinence. They support the usefulness of nonhuman primates as translatable surrogates for pathophysiological studies of urinary sphincter deficiency and testing novel therapies for that condition.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27101, USA.
authors.forename: Sherif
authors.initials: S
authors.lastname: Badra
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Ashley
authors.initials: A
authors.lastname: Dean
authors.forename: Sherif
authors.initials: S
authors.lastname: Mourad
authors.forename: J Koudy
authors.initials: JK
authors.lastname: Williams
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008252:Macaca fascicularis; D060525:Pudendal Nerve; D014521:Urethra / Q000294:innervation; D014550:Urinary Incontinence, Stress