Computer simulation of local anesthetic effects using a mathematical model of myelinated nerve.

A mathematical model of myelinated axon was programmed for digital computer solution of the consequences of the conduction characteristics when the model membrane was affected by local anesthetics simulated by alteration of the ionic conductance parameter. The effects of tetrodotoxin on impulse conduction were studied in detail by means of a systematic reduction in sodium conductance in 1 to 10 nodes of Ranvier. Rhis technique simulates the method used experimentally and clinically to achieve a conduction block with the circumscribed application of local anesthetics to segments of nerve axons or nerve trunks. The analysis of the tetrodotoxin "dose-response" relationships revealed the fact that the model myelinated axon could support three types of conduction when depressed by this drug. One type of conduction of a subnormal impulse at the nodes of Ranvier; a second is characterized by a form of decremental conduction in which the rate of decrement of the nodal impulse is linear with distance. The third type is a second form of decremental conduction which is exponential in configuration and is seen when the g(Na) at the nodes of Ranvier is reduced to less than 27% of normal. Parallel experiments were performed to simulate the effects of lidocaine and some significant differences were observed. Analysis of the action potentials within the internodel region suggests that, although immune to drug action in the model, the internodal segment affects the generation of action potentials at the nodes. A commentary is presented on the limitations of the model as it reflects known pharmacologic relationships in real myelinated axons.