Proposal for a Standard Test to Compare the Efficacy of Oximes on Organophosphate-Blocked Neuromuscular Transmission In vitro

摘要

The present protocol describes a method to test in vitro the direct action and the reactivating effects of oximes and related compounds on organophosphate-blocked neuromuscular transmission. The test procedure or variations thereof has been successfully used during the past 20 years in the Medical Biological Laboratory TNO and is based on the following considerations: (1) high frequency stimulation (25-200 Hz) of the unpoisoned preparation during periods of e.g. 3 seconds of the motor nerve causes a sustained tetanic contraction of the attached striated muscle, (2) upon administration of increasing amounts of an organophosphorus cholinesterase inhibitor the ability to sustain a tetanus decreases, a process which starts at the tetanus resulting from stimulation with the highest frequency. Ultimately, only a first twitchlike contraction is detectable at the beginning of the stimulation period, whereas no contraction can be observed during the remainder of the stimulation period. If nerve conduction and muscle contractility are not affected, as is the case here, the degree of loss of tetanic ability at the different frequencies is a yardstick for the failure of neuromuscular transmission, (3) oxime administration causes a reversal of this process.