Concentration Dependence of Lidocaine-induced Irreversible Conduction Loss in Frog Nerve

Abstract

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.