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

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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.

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Abbreviations

Group A:

No intervention group

Group B:

Sphincterotomy and primary repair

Group C:

Sphincterotomy, primary repair and CXCL12

D:

Duration of contraction

Tmax :

Time to peak of contraction

PΔ:

Change in contraction pressure from baseline

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Authors and Affiliations

  1. Department of Urology, Wake Forest Baptist Medical Center, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Amr S. El Haraki, Catherine A. Matthews & Gopal H. Badlani

  2. Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA

    S. Lankford & Koudy J. Williams

  3. Department of Pathology, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA

    Wencheng Li

Authors
  1. Amr S. El Haraki
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  2. S. Lankford
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  3. Wencheng Li
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  4. Koudy J. Williams
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  5. Catherine A. Matthews
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  6. Gopal H. Badlani
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Contributions

AS El Haraki: Rat measurements and surgery, data analysis and manuscript writing

S Lankford: Rat measurements, data collection and surgery

Wencheng Li: qualitative histologic analysis

JK Williams: Project development, manuscript editing

C Matthews: Manuscript writing

GH Badlani: Principal investigator, project development, manuscript editing

Corresponding author

Correspondence to Amr S. El Haraki.

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El Haraki, A.S., Lankford, S., Li, W. et al. Chemokine therapy for anal sphincter injury in a rat model: a pilot study. Int Urogynecol J 33, 3283–3289 (2022). https://doi.org/10.1007/s00192-022-05195-5

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  • DOI: https://doi.org/10.1007/s00192-022-05195-5

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