Concentration is a causal factor in local anesthetic nerve toxicity. Therefore, it is essential to define a concentration below which injury does not occur. We explored the relation of lidocaine concentration and nonreversible block after drug washout in frog sciatic nerve.Frog sciatic nerve was mounted in sucrose-gap or extracellular recording chambers. The observed compound action potential in response to a supramaximal stimulus was used as a measure of nonreversible block after applying lidocaine in a range of concentrations (0.5-200 mM for 15 min) and then washing off (for as long as 180 min).Lidocaine causes a nonreversible block after washout that begins at concentrations as low as 40 mM and increases in a graded fashion with increasing concentrations to complete ablation of the compound action potential at 80 mM (approximately 2%). Extended storage of frogs (5 weeks) at 4 degrees C makes the nerves more resistant to the effects of lidocaine. The presence of nifedipine (10(-5) M), an L-type calcium-channel blocker, makes the nerves more resistant to lidocaine as well.Lidocaine induces a nonreversible loss of impulse activity in frog nerve in a progressive fashion with increasing drug concentration, beginning at 40 mM (approximately 1.0%). The range of lidocaine that produces such changes in mammalian nerve awaits determination.
