The influence of motor nerve tetanization on the effect of organophosphorus cholinesterase inhibitors on neuromuscular transmission

Abstract

1. The changes in the activity of synaptic cholinesterases (ChE) of the ant. tibial muscle in the anaesthetized cat were detected by recording the changes of the blocking activity of acetylcholine (ACh) and comparing them with the blocking activity of carbaminoylcholine (carbachol) injected intra-arterially or intravenously. After the administration of organophosphorus inhibitors (OPI) of ChE the ACh blocking dose diminished 500 to 2000-fold but the carbachol blocking dose did not change. In 4-6 h after the injection of OPI the ACh blocking dose increased again 8 to 15-fold, but the dose of carbachol still remained unchanged. The transmission of high frequency impulses improved after OPI in parallel with the decrease of the ACh blocking activity. Thus the synaptic ChE is partly restored in a few hours after its irreversible inhibition with OPI. 2. Tetanization of the motor nerve (50-60 Hz, 10 min), started simultaneously with the intravenous injection of OPI (armine Gd-42), diminished the impairment of neuromuscular transmission. On the side of tetanization the ACh blocking action was less pronounced and the transmission of high frequency impulses better than on the control side. Thus the tetanization produced some protection of synaptic ChE against inhibition by OPI. The protective effect of tetanization was absent when the tetanization was performed before the injection of OPI or was started 10-20 min after the injection of OPI. 3. The protective effect of tetanization was also observed on the isolated phrenic nerve diaphragm preparation of the rat. 4. The possible mechanisms of the protective effect of tetanization are discussed.