Effect of atropine, HLö 7 and HI 6 on respiratory and circulatory function in guinea-pigs poisoned by O-ethyl S-[2-(diisopropylamino) ethyl] methylphosponothioate (VX).
In a guinea-pig model with on-line respiratory and circulatory monitoring the therapeutic efficacy of atropine, HLö 7 and HI 6 in VX poisoning was compared. In female urethane-anaesthetized Pirbright-white guinea-pigs the a. carotis, v. jugularis and trachea were cannulated. After base line measurements the animals received VX (22.5, 45 or 90 micrograms/kg = 5, 10 or 20 x LD50) intravenously and 2 min. later the antidotes: HLö 7 or HI 6 (30 mumol/kg, each) or atropine 10 mg/kg or a combination of atropine and one of the oximes (all intravenously). Respiratory and circulatory parameters were recorded for 60 min. or until death of the animal. Erythrocyte, brain and diaphragm acetylcholinesterase (AChE) activity was determined after the experiment. VX poisoning caused a rapid respiratory arrest within 4-5 min. Atropine treatment was effective in improving the respiratory function after VX, 22.5 micrograms/kg, but had only a small effect after the higher VX doses. The treatment of VX (10 or 20 x LD50) poisoned animals with oxime plus atropine improved respiration to various extents, restored circulation and prolonged the survival time, HLö 7 being more effective than HI 6 after VX 90 micrograms/kg. Oximes alone were completely ineffective. Erythrocyte and diaphragm AChE was reactivated by HLö 7 and, less effectively, by HI 6, while brain AChE remained almost completely inhibited in all groups. The results of this investigation demonstrate a reasonable efficacy of atropine after lower VX doses and of HLö 7 and HI 6 (plus atropine) after high-dose VX poisoning, HLö 7 being slightly more effective than HI 6.
Worek
F
F
Institute of Pharmacology and Toxicology, Federal Armed Forces Medical Academy, Garching, Germany.
Kirchner
T
T
Szinicz
L
L
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004338:Drug Combinations; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D009946:Organothiophosphorus Compounds / Q000506:poisoning*; D010091:Oximes; D011041:Poisoning / Q000188:drug therapy / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects
D000110:Acetylcholinesterase; D001285:Atropine; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D004338:Drug Combinations; D009946:Organothiophosphorus Compounds; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; C009680:VX-agent; C022870:asoxime chloride