Changes in denervated skeletal muscle of amiodarone-fed mice.

Prolonged dosing of mice with amiodarone produced a myopathy characterized by autophagic vacuolation and phospholipid inclusions. A previous morphological study had shown that amiodarone did not affect the rate of nerve regeneration after sciatic nerve crush. In the present study, reinnervation was assessed by the reappearance of miniature endplate potentials that confirmed that axonal regeneration and motor reinnervation was not affected by amiodarone. However, there was a marked delay in the recovery of motor function in the amiodarone-treated mice. Denervation was found to induce an extensive necrosis of muscle fibers in the deeper parts of fast-twitch muscles. Histochemical studies showed that type 1 fibers were spared, necrosis affecting mainly type 2 fibers with relatively high oxidative enzyme activity (fast-twitch oxidative fibers). Biochemical studies showed a significant increase in the amount of amiodarone and its metabolite in denervated muscle of amiodarone-treated mice when compared with contralateral, normally innervated muscles.