PD34-02 CHEMOKINE THERAPY FOR ANAL SPHINCTER INJURY: DEVELOPMENT OF A RAT MODEL OF CHRONIC INJURY

Abstract

You have accessJournal of UrologyCME1 May 2022PD34-02 CHEMOKINE THERAPY FOR ANAL SPHINCTER INJURY: DEVELOPMENT OF A RAT MODEL OF CHRONIC INJURY Amr El Haraki, Shannon Lankford, Wencheng Li, Catherine Matthews, Koudy Williams, and Gopal Badlani Amr El HarakiAmr El Haraki More articles by this author , Shannon LankfordShannon Lankford More articles by this author , Wencheng LiWencheng Li More articles by this author , Catherine MatthewsCatherine Matthews More articles by this author , Koudy WilliamsKoudy Williams More articles by this author , and Gopal BadlaniGopal Badlani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002585.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Stromal cell-derived factor 1 (CXCL12) is a potential alternative to stem cell augmentation therapy for management of fecal incontinence. The objective of this study was to develop a rat model of anal sphincter injury and determine the predictability of using anal manometry in the rat model to collaborate histologic findings. METHODS: Adult female rats were divided into three groups: Group A was a control group that did not undergo surgery; group B had an anal sphincterotomy with primary surgical repair and group C had an anal sphincterotomy with primary surgical repair and intra-sphincteric injection of 200 ng of CXCL12 at 6 weeks post-injury. All rats underwent anal manometry measurements at baseline and at 6 weeks and 12 weeks post-injury. In each rat, the three strongest contractions were chosen for measurement and mean values of the following: total duration (D), time to peak (Tmax), and difference between maximal and minimal pressure value (P∆) were calculated and compared between groups. Mason-Trichrome staining of the anal sphincters was performed and histologic analysis was obtained. RESULTS: 16 rats, 5 in Group A, 5 in Group B and 6 in Group C were investigated. At baseline and at 6 weeks, there were no statistically significant differences between D, Tmax and P∆ of Groups A, B and C. At 12-week manometry, the total duration of contractions on anal manometry was significantly less in Group C compared to Groups A and B (3.65, 5.5, 5.3 p<0.01) as was time to peak of contraction at 12 weeks (1.6,2.1,3.1 p<0.01); however, group C had a significantly higher P∆ at 12 weeks compared to Groups A and B (2.25,1.4, 0.34 p<0.01). On histologic analysis, there were no statistically significant differences in the ratio of muscle to collagen at the site of injury between the different groups, however, muscle fibers were significantly smaller in group C and less per bundle than groups A and B. CONCLUSIONS: Delayed injection of CXCL12 seemed to enhance the magnitude of anal sphincter contractions on anorectal manometry in a rat model of anal sphincter injury. The mechanism of increased anal sphincter contraction magnitude was not explained by histologic differences in explanted specimens. A deficit in the rat model, the rat's intrinsic self-healing ability and difficulty to accurately measure direct sphincter activity, likely contributed to this discrepancy. A better animal model will be needed in future experiments of fecal incontinence to assess the application of regenerative therapy. Source of Funding: Wake Forest Institute of Regenerative Medicine © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e559 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amr El Haraki More articles by this author Shannon Lankford More articles by this author Wencheng Li More articles by this author Catherine Matthews More articles by this author Koudy Williams More articles by this author Gopal Badlani More articles by this author Expand All Advertisement PDF DownloadLoading ...