Tacrolimus Does Not Affect Early Wound Healing in a Rodent Model of Bowel Anastomoses and Abdominal Wall Closure

BACKGROUND: Use of immunosuppressant drugs has been associated with complications in wound healing. The calcineurin inhibitor tacrolimus is thought to have a relatively low complication rate, but preclinical research has yielded contradictory data, prompting the current comprehensive study. METHODS: Three groups of 33 male Wistar rats received a daily subcutaneous dose of 0,5, 2 or 5 mg/kg tacrolimus. A control group received saline. On day 0 a resection of 1 cm ileum and 1 cm colon was performed, and end-to-end anastomoses were constructed. Ten rats of each group were killed on day 3 and day 5 and the remaining animals on day 7. Both anastomoses and the wound in the abdominal wall were analyzed. Wound strength was the primary outcome parameter. RESULTS: Mean strength of the abdominal wall increased significantly over time in all groups (p<0.0001). Both the breaking strength and the bursting pressure of the ileum and colon anastomoses followed the same pattern. No differences were observed between control and experimental groups. In addition, no consistent differences were found between groups regarding wound hydroxyproline content and the activities of matrix metalloproteinase-2 and -9. CONCLUSION: Tacrolimus does not affect early wound healing.