Vagal tone monitoring: a potential indicator of anti-cholinesterase exposure in Macaca mulatta.

A vagal tone monitor (VTM) was used to evaluate cardiac rhythm changes in Rhesus monkeys (Macaca mulatta) after intramuscular (i.m.) administration of an anti-cholinergic (atropine sulfate), two carbamates (pyridostigmine bromide and physostigmine salicylate), and combinations of pyridostigmine and atropine. Twelve monkeys were studied in 4 experiments using Latin Square blind designs. Experiment I tested the VTM responses to atropine sulfate injections of 0, 14, 44 and 140 micrograms/kg. Experiment II tested the responses to 0, 100, 200 and 400 micrograms/kg pyridostigmine injections. Experiment III tested the responses to physostigmine injections of 0, 25, 50 and 100 micrograms/kg. Experiment IV tested the same atropine sulfate treatments as Experiment I 30 min after a pyridostigmine pretreatment of 200 micrograms/kg. The VTM analysis produced an estimate of vagal tone (V) every 30 s, and V was averaged over 15 min. The results indicated that V responded more to physostigmine and atropine than pyridostigmine. There was also an attenuated response to atropine following pyridostigmine pretreatment. The attenuated response had been demonstrated earlier in organophosphate (OP) treated dogs. The results suggest that V may be used as a non-invasive indicator of cholinergic drug effects.