CARDIORESPIRATORY FUNCTION IN NERVE AGENT POISONED AND OXIME PLUS ATROPINE TREATED GUINEA-PIGS - EFFECT OF PYRIDOSTIGMINE PRETREATMENT

The effect of pyridostigmine pretreatment on the efficacy of oxime + a tropine treatment in sarin and VX poisoning was investigated in a guin ea-pig model with on-line monitoring of respiratory and circulatory pa rameters. The carotid artery, jugular vein and trachea were cannulated in female urethane-anesthetized Pirbright-white guinea-pigs. After ba seline measurements the animals received pyridostigmine (PYR, 0.05 mu mol/kg, i.v.), 30 min later sarin (100 or 200 mu g/kg = 5 or 10xLD(50) , i.v.) or VX (45 or 90 mu g/kg = 10 or 20xLD(50), i.v.), followed 2 m in later by atropine (10 mg/kg, i.v.) plus HI 6 or HLo double over dot 7 (30 mu mol/kg each, i.v.). Sixty-minute survival time and rate and respiratory and circulatory parameters were recorded. Diaphragm acetyl cholinesterase(AChE) activity was determined spectrophotometrically. I dentical groups without PYR were included for comparison. With regard to survival time and rate, PYR pretreatment slightly improved the effi cacy of HI 6 plus atropine in sarin 5xLD(50) poisoned animals, reduced the efficacy of oxime + atropine treatment in the other sarin groups and had no effect in VX poisoning. Compared to non-pretreated oxime atropine groups, PYR slightly improved respiratory function in sarin a nd in VX poisoning (only HI 6). PYR did not affect circulatory functio n in VX poisoning but reduced circulatory parameters in sarin poisonin g to varying extent's. The oxime efficacy in reactivating diaphragm AC hE decreased in the order sarin > VX without significant differences b etween pretreated and non-pretreated groups. The data suggest that pyr idostigmine pretreatment does not enhance the efficacy of oxime + atro pine in sarin or VX poisoning.