Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro.
High concentrations of lidocaine induce irreversible conduction block with little effect on resting membrane potential (Em). We assumed the mechanism of persistent neurologic deficit caused by local anesthetics may result from neural death, as represented by the loss of Em. We investigated the effects of lidocaine on Em and action potential (AP) in single crayfish giant axons in vitro. Axons were perfused with two doses of lidocaine for either 15 or 30 min, and they were continuously washed. No axons exposed to 80 mM lidocaine for 30 min showed recovery of AP and Em. Those exposed to 40 mM for 30 min and 80 mM for 15 min showed a return to baseline for Em, but no recovery of AP. Those exposed to 40 mM lidocaine for 15 min showed full recovery of Em and AP immediately after washing. The membrane depolarization was significantly greater during exposure to 80 mM lidocaine for 30 min than in other groups. We conclude that lidocaine has a direct neurotoxic effect on crayfish giant axons and that the generation of AP is more vulnerable than the maintenance of Em. The irreversibility of AP and Em is dose- and time-dependent.


CONCLUSIONS
Highly concentrated lidocaine induced an irreversible conduction block and a complete loss of resting membrane potential in crayfish giant axons in vitro. Our results may represent a possible explanation for various grades of local anesthetic-induced neurotoxicity in clinical cases if the same toxicity occurs in mammalian nerves in vivo.
Kanai
Y
Y
Department of Anesthesiology, Miyazaki Medical College, Kiyotake, Japan.
Katsuki
H
H
Takasaki
M
M
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008012:Lidocaine / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects
D000779:Anesthetics, Local; D008012:Lidocaine