title: A novel animal model for external anal sphincter insufficiency.
abstract: OBJECTIVE
  Reliable animal models are essential to evaluate future therapeutic options like cell-based therapies for external anal sphincter insufficiency. The goal of our study was to describe the most reliable model for external sphincter muscle insufficiency by comparing three different methods to create sphincter muscle damage.
  
  
  METHODS
  In an experimental animal study, female Lewis rats (200-250 g) were randomly assigned to three treatment groups (n = 5, each group). The external sphincter muscle was weakened in the left dorsal quadrant by microsurgical excision, cryosurgery, or electrocoagulation by diathermy. Functional evaluation included in vivo measurements of resting pressure, spontaneous muscle contraction, and contraction in response to electrical stimulation of the afferent nerve at baseline and at 2, 4, and 6 weeks after sphincter injury. Masson's trichrome staining and immunofluorescence for skeletal muscle markers was performed for morphological analysis.
  
  
  RESULTS
  Peak contraction after electrical stimulation was significantly decreased after sphincter injury in all groups. Contraction forces recovered partially after cryosurgery and electrocoagulation but not after microsurgical excision. Morphological analysis revealed an incomplete destruction of the external sphincter muscle in the cryosurgery and electrocoagulation groups compared to the microsurgery group.
  
  
  CONCLUSIONS
  For the first time, three different models of external sphincter muscle insufficiency were directly compared. The animal model using microsurgical sphincter destruction offers the highest level of consistency regarding tissue damage and sphincter insufficiency, and therefore represents the most reliable model to evaluate future therapeutic options. In addition, this study represents a novel model to specifically test the external sphincter muscle function.
authors.affiliation: Laboratory for Urologic Tissue Engineering and Stem Cell Therapy, Department of Urology, University Hospital Zürich, Frauenklinikstrasse 10, 8091, Zürich, Switzerland, lukas.bruegger@insel.ch.
authors.forename: Lukas
authors.initials: L
authors.lastname: Brügger
authors.forename: Roman
authors.initials: R
authors.lastname: Inglin
authors.forename: Daniel
authors.initials: D
authors.lastname: Candinas
authors.forename: Tullio
authors.initials: T
authors.lastname: Sulser
authors.forename: Daniel
authors.initials: D
authors.lastname: Eberli
mesh_terms: D001003:Anal Canal / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D000818:Animals; D003452:Cryosurgery; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004564:Electrocoagulation; D005242:Fecal Incontinence / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D007150:Immunohistochemistry; D008365:Manometry; D008866:Microsurgery; D009119:Muscle Contraction; D011897:Random Allocation; D011917:Rats, Inbred Lew