Worek_1995_Human.Exp.Toxicol_14_634

1. The effect of pyridostigmine on cardiorespiratory function after oxime + atropine injection was investigated in tabun poisoned guinea-pigs and without tabun poisoning. 2. The trachea, a carotid artery and jugular vein were cannulated in female urethane-anaesthetised Pirbright-white guinea-pigs. After baseline measurements the animals received pyridostigmine (0.05 mumol kg-1) and 30 min later atropine (29.5 mumol kg-1) plus obidoxime, HI 6 or HL 7 (30 or 100 mumol kg-1) or tabun (1.85 mumol kg-1 = 5 x LD50) followed by oxime + atropine treatment (all i.v.). Erythrocyte, brain and diaphragm acetylcholinesterase (AChE) activity were determined. Similar groups without pretreatment were included for comparison. 3. Pyridostigmine aggravated the oxime + atropine induced hypotension and prevented the increase in heart rate but not the respiratory stimulation. The pyridostigmine inhibited AChE recovered only in the 100 mumol kg-1 kg oxime groups at the end of the experiment. 4. In tabun poisoning, pyridostigmine reduced the oxime + atropine induced circulatory recovery and decreased the survival time and rate. It did not affect the therapeutic oxime + atropine effect on respiratory function. 5. These results suggest that pyridostigmine enhances oxime + atropine related circulatory depression which may be the reason for the reduced efficacy of oxime + atropine treatment in tabun poisoning. The possible mechanisms are discussed.