A novel animal model for external anal sphincter insufficiency

Abstract

Abstract:Purpose: 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. Mason 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 external sphincter muscle function.Additional Information:Question Response Was this manuscript been published previously or under consideration in wholeThis Manuscript has not been published in whole or in part elsewhere. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationor in part somewhere else?2. Was this manuscript in its present form has been read and approved to submission to "International Journal of colorectal disease" for publication by all participated authors?This manuscript in its present form has been read and approved to submission to "International Journal of colorectal disease" for publication by all participated authors. Acknowledgments:The authors thank Meline Stoelting, Souzan Salemi, and Fatma Kivrak for the introduction in analyzing techniques and for technical assistance.4. Conflict of interest or financial disclosure:The authors declare no conflict of interest or financial disclosure. Do you certify that this research is entirely original?This research is entirely original.6. Which of the following government agencies provided funding for your research?No government agency provided funding for this research. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15...

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“…After a 5 min adaptation period, spontaneous contraction waves were recorded for 5-10 min. To determine the resting pressure, the balloon probe was drawn out in a contraction interval, and the resulting difference from the baseline pressure (the mean of 5 intervals) was calculated 15 (Fig. 2).…”