Amr S El Haraki1, S Lankford2, Wencheng Li3, Koudy J Williams2, Catherine A Matthews4, Gopal H Badlani4. 1. Department of Urology, Wake Forest Baptist Medical Center, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA. aelharak@wakehealth.edu. 2. Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA. 3. Department of Pathology, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA. 4. Department of Urology, Wake Forest Baptist Medical Center, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA.
Abstract
INTRODUCTION AND HYPOTHESIS: To determine whether delayed administration of CXCL12 alters anorectal manometric pressures and histology in rats following anal sphincterotomy compared to primary surgical repair alone. METHODS: Adult female rats were divided into three groups: A, a control group that did not undergo surgery; B, anal sphincterotomy with primary surgical repair; C, anal sphincterotomy with primary surgical repair and intra-sphincteric injection of CXCL12 at 6 weeks post-injury. All rats underwent anal manometry measurements at baseline and at 6 and 12 weeks post-injury. Histologic analysis of the anal sphincters was also performed. RESULTS: At baseline and 6 weeks, there were no statistically significant differences among 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). There were no statistically significant differences in the ratio of muscle to collagen at the site of injury; however, muscle fibers were significantly smaller in group C and less per bundle than the other groups. CONCLUSIONS: Administration of chemokine therapy at 6 weeks post-repair using CXCL12 enhanced the magnitude of anal sphincter contractions in a rat model of anal sphincter injury but decreased overall duration of contraction. Increased anal sphincter contraction magnitude was not explained by histologic differences in explanted specimens.
INTRODUCTION AND HYPOTHESIS: To determine whether delayed administration of CXCL12 alters anorectal manometric pressures and histology in rats following anal sphincterotomy compared to primary surgical repair alone. METHODS: Adult female rats were divided into three groups: A, a control group that did not undergo surgery; B, anal sphincterotomy with primary surgical repair; C, anal sphincterotomy with primary surgical repair and intra-sphincteric injection of CXCL12 at 6 weeks post-injury. All rats underwent anal manometry measurements at baseline and at 6 and 12 weeks post-injury. Histologic analysis of the anal sphincters was also performed. RESULTS: At baseline and 6 weeks, there were no statistically significant differences among 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). There were no statistically significant differences in the ratio of muscle to collagen at the site of injury; however, muscle fibers were significantly smaller in group C and less per bundle than the other groups. CONCLUSIONS: Administration of chemokine therapy at 6 weeks post-repair using CXCL12 enhanced the magnitude of anal sphincter contractions in a rat model of anal sphincter injury but decreased overall duration of contraction. Increased anal sphincter contraction magnitude was not explained by histologic differences in explanted specimens.
Authors: Massarat Zutshi; Levilester B Salcedo; Paul J Zaszczurynski; Tracy L Hull; Robert S Butler; Margot S Damaser Journal: Dis Colon Rectum Date: 2009-07 Impact factor: 4.585