The Effect of Low-Dose Tacrolimus on Recurrent Laryngeal Nerve Regeneration in Pigs: A Pilot Study

Abstract

Edward C Toll, Pamela J Murison, Alan Jones, Paul J Kingham, Tina Sedaghati, Alexander M Seifalian, Martin A Birchall

Objective: The functional neurotrophic effects of systemic tacrolimus in a sub-immunosuppressive regimen in the minipig model of laryngeal reinnervation were investigated. Methods: Right recurrent laryngeal nerve transection and phrenic-abductor branch of recurrent laryngeal nerve anastomosis were performed in two minipigs that were administered low-dose oral tacrolimus (0.125 mg/kg) for one month. Vocal cord abduction at four months was rated by two blinded expert assessors on a four-point Likert scale from poor (1) to complete (4), and compared with five fully matched historical control animals that received the same surgery but no other interventions. Results: Right vocal cord abduction was more complete in tacrolimus-treated animals than controls (mean abduction score 2.3 vs. 1.5, p=0.019). Conclusion: Tacrolimus may have an important role in laryngeal reinnervation following allograft transplantation, and low-dose regimens may have applications in cranial and peripheral nerve injuries or in the reinnervation of tissue-engineered laryngeal constructs, but further studies are required