Improved Early Muscle Recovery Using FK506 in a Rat Nerve-Repair Model

The authors hypothesized that FK506 improves maximal muscle force (P₀) recovery during early muscle reinnervation. Rat peroneal nerve was unilaterally cut and repaired. Rats received subcutaneous injections of vehicle (controls) or FK506 at 1 mg/kg (FK506-1MG) or 5 mg/kg (FK506-5MG) for 3 weeks. Extensor digitorum longus (EDL) isometric muscle P₀ was measured bilaterally 4 weeks postoperatively. FK506 treatment adversely affected body mass. With body mass as a covariate, the P₀ for denervated-reinnervated muscle in the FK506-5MG group was statistically significantly higher by 34 percent and 32 percent, compared with controls and FK506-1MG groups. There was no group difference for the contralateral, nerve-intact EDL muscle P₀, when loss of body mass was considered. NCAM immunohistologic data showed significantly better reinnervation of the denervated muscle in a dose-dependent fashion. Thus, FK506 treatment at high dose improves early recovery of force in denervated-reinnervated muscle, following nerve repair, when loss of body mass is considered.

KEYWORDS

Tacrolimus - denervation - muscle

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