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Amiodarone‐induced experimental acute neuropathy in rats
Author(s) -
Santoro Lucio,
Barbieri Fabrizio,
Nucciotti Renato,
Battaglia Francesco,
Crispi Francesco,
Ragno M.,
Greco P.,
Caruso G.
Publication year - 1992
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.880150707
Subject(s) - amiodarone , axon , medicine , microinjection , sciatic nerve , nerve conduction velocity , electrophysiology , tibial nerve , anesthesia , peripheral neuropathy , axonal degeneration , endocrinology , anatomy , pathology , stimulation , diabetes mellitus , atrial fibrillation
Amiodarone was injected endoneurially at increasing doses into the exposed tibial nerve of rats to study its electrophysiologic and pathologic effects on peripheral nerve fibers. Forty‐five male Wistar rats were used, and each of the following concentrations was injected into 15 nerves: 25 μg/mL, 50 μg/mL, and 100 μg/mL. Microinjection of a 25 μg/mL concentration of amiodarone resulted in a subacute, incomplete conduction block evident at day 3 postinjection. This conduction block remained stable until day 10 and recovery was complete at day 35. Microinjection of a 50 μg/mL concentration of amiodarone produced a faster evolving conduction block, and significant axon degeneration (approximately 40% of fibers). Injection of a 100 μg/mL concentration resulted in severe acute motor axon degeneration followed by complete but delayed regeneration. Results of morphological studies closely correlated with electrophysiological findings. Amiodarone thus seems to have a direct toxic effect on axons at high concentrations in the peripheral nerve, and we suggest that different pathological changes described in human amiodarone neuropathy could be related to different concentrations of the drug in the nerve, perhaps due to variability of blood‐nerve barrier efficacy.