EFFECT OF ATROPINE, HLO7 AND HI6 ON RESPIRATORY AND CIRCULATORY FUNCTION IN GUINEA-PIGS POISONED BY O-ETHYL S-[2-(DIISOPROPYLAMINO)ETHYL] METHYLPHOSPHONOTHIOATE(VX)

In a guinea-pig model with on-line respiratory and circulatory monitor ing the therapeutic efficacy of atropine, HLo 7 and HI 6 in VX poisoni ng was compared. In female urethane-anaesthetized Pirbright-white guin ea-pigs the a. carotis, v. jugularis and trachea were cannulated. Afte r base line measurements the animals received VX (22.5, 45 or 90 mu g/ kg=5, 10 or 20xLD(50)) intravenously and 2 min. later the antidotes: H Lo 7 or HI 6 (30 mu mol/kg, each) or atropine 10 mg/kg or a combinatio n of atropine and one of the oximes (all intravenously). Respiratory a nd circulatory parameters were recorded for 60 min. or until death of the animal. Erythrocyte, brain and diaphragm acetylcholinesterase (ACh E) activity was determined after the experiment. VX poisoning caused a rapid respiratory arrest within 4-5 min. Atropine treatment was effec tive in improving the respiratory function after VX, 22.5 mu g/kg, but had only a small effect after the higher VX doses. The treatment of V X (10 or 20xLD(50)) poisoned animals with oxime plus atropine improved respiration to various extents, restored circulation and prolonged th e survival time, HLo 7 being more effective than HI 6 after VX 90 mu g /kg. Grimes alone were completely ineffective. Erythrocyte and diaphra gm AChE was reactivated by HLo 7 and, less effectively, by HI 6, while brain AChE remained almost completely inhibited in all groups. The re sults of this investigation demonstrate a reasonable efficacy of atrop ine after lower VX doses and of HLo 7 and HI 6 (plus atropine) after h igh-dose VX poisoning, HLo 7 being slightly more effective than HI 6.