F. Worek et al., EFFECT OF PYRIDOSTIGMINE PRETREATMENT ON CARDIORESPIRATORY FUNCTION IN TABUN POISONING, Human & experimental toxicology, 14(8), 1995, pp. 634-642
1 The effect of pyridostigmine on cardiorespiratory function after oxi
me+atropine injection was investigated in tabun poisoned guinea-pigs a
nd without tabun poisoning. 2 The trachea, a carotid artery and jugula
r vein were cannulated in female urethane-anaesthetised Pirbright-whit
e guinea-pigs. After baseline measurements the animals received pyrido
stigmine (0.05 mu mol kg(-1)) and 30 min later atropine (29.5 mu mol k
g(-1)) plus obidoxime, HI 6 or HLo 7 (30 or 100 mu mol kg(-1)) or tabu
n (1.85 mu mol kg(-1) = 5 x LD(50)) followed by oxime+atropine treatme
nt (all i.v.). Erythrocyte, brain and diaphragm acetylcholinesterase (
AChE) activity were determined. Similar groups without pretreatment we
re included for comparison. 3 Pyridostigmine aggravated the oxime+atro
pine induced hypotension and prevented the increase in heart rate but
not the respiratory stimulation. The pyridostigmine inhibited AChE rec
overed only in the 100 mu mol kg(-1) kg oxime groups at the end of the
experiment. 4 In tabun poisoning, pyridostigmine reduced the oxime+at
ropine induced circulatory recovery and decreased the survival time an
d rate. It did not affect the therapeutic oxime+atropine effect on res
piratory function. 5 These results suggest that pyridostigmine enhance
s oxime+atropine related circulatory depression which may be the reaso
n for the reduced efficacy of oxime+atropine treatment in tabun poison
ing. The possible mechanisms are discussed.