Chemokine therapy for anal sphincter injury in a rat model: a pilot study

• Published in: International Urogynecology Journal 2022-11, Vol.33 (11), p.3283-3289
• Main Authors: El Haraki, Amr S., Lankford, S., Li, Wencheng, Williams, Koudy J., Matthews, Catherine A., Badlani, Gopal H.
• Format: Article
• Language: English
• Subjects: Chemokines; Childbirth & labor; Cytokines; Fecal incontinence; Feces; Gynecology; Hypotheses; Medicine; Medicine & Public Health; Original Article; Regenerative medicine; Rodents; Urology
• ISSN: 0937-3462; 1433-3023
• DOI: 10.1007/s00192-022-05195-5

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, T max 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.