Inhibition by local anaesthetic drugs at low and high stimulation frequencies: A comparison between the isolated phrenic nerve of the rat and the phrenic nerve-diaphragm preparation

Abstract

The effects of lidocaine (0.25 mM), prilocaine (0.3 mM), diphenylhydantoin (0.24 mM), tetraeaine (0.005 mM) and dibucaine (0.002 mM) on the isolated rat phrenic nerve, neuromuseular transmission and the directly stimulated rat diaphragm, were observed at low (twitch) and high (tetanic) stimulation frequency. The phrenic nerve compound action potential and muscle tension during indirect and direct stimulation were compared. At high frequency stimulation all drugs caused high frequency inhibition of both nerve and muscle. The high frequency inhibition was usually biphasic with an initial decrease in the amplitude of compound action potential and tetanic tension and a subsequent stabilization at a reduced plateau level. The duration of the initial phase increased with the potency of the drugs and was similar for nerve and muscle. A specific high frequency inhibition during indirect stimulation was found with diphenylhydantoin and prilocaine, indicating pre- and post-synaptic inhibition of neuromuscular transmission. At low frequency stimulation, the drugs induced a basal inhibition of the nerve compound action potential. In spite of that, the twitches were not depressed during indirect stimulation of the muscle, illustrating the margin of safety with neuromuscular transmission. These results indicate that the action of the drug was similar at the excitable nerve and muscle membranes when stimulated at high frequency, but different at low frequency stimulation.