Cardiorespiratory function in nerve agent poisoned and oxime + atropine treated guinea-pigs: effect of pyridostigmine pretreatment.

Abstract

The effect of pyridostigmine pretreatment on the efficacy of oxime + atropine treatment in sarin and VX poisoning was investigated in a guinea-pig model with on-line monitoring of respiratory and circulatory parameters. The carotid artery, jugular vein and trachea were cannulated in female urethane-anesthetized Pirbright-white guinea-pigs. After baseline measurements the animals received pyridostigmine (PYR, 0.05 mumol/kg, i.v.), 30 min later sarin (100 or 200 micrograms/kg = 5 or 10 x LD50, i.v.) or VX (45 or 90 micrograms/kg = 10 or 20 x LD50, i.v.), followed 2 min later by atropine (10 mg/kg, i.v.) plus HI 6 or HLö 7 (30 mumol/kg each, i.v.). Sixty-minute survival time and rate and respiratory and circulatory parameters were recorded. Diaphragm acetylcholinesterase (AChE) activity was determined spectrophotometrically. Identical groups without PYR were included for comparison. With regard to survival time and rate, PYR pretreatment slightly improved the efficacy of HI 6 plus atropine in sarin 5 x LD50 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 and in VX poisoning (only HI 6). PYR did not affect circulatory function in VX poisoning but reduced circulatory parameters in sarin poisoning to varying extent's. The oxime efficacy in reactivating diaphragm AChE decreased in the order sarin > VX without significant differences between pretreated and non-pretreated groups. The data suggest that pyridostigmine pretreatment does not enhance the efficacy of oxime + atropine in sarin or VX poisoning.