TREATMENT OF TABUN POISONED GUINEA-PIGS WITH ATROPINE, HLO-7 OR HI-6 - EFFECT ON RESPIRATORY AND CIRCULATORY FUNCTION

The oxime HI 6 (in combination with atropine) is considered to be an e ffective antidote in soman intoxication but was Shown to be less effec tive in tabun poisoning. In contrast to HI 6, first in vitro studies w ith HLo 7 demonstrated a reasonable reactivating potency at acetylchol inesterase (AChE) inhibited by soman and tabun. Therefore, the therape utic efficacy of HLo 7, HI 6 and obidoxime (with and without atropine) was compared in tabun poisoned guinea-pigs. In addition, the therapeu tic effect of atropine in guinea-pigs poisoned by Various doses of tab un was investigated. Female Pirbright-white guineapigs were anaestheti zed with urethane (1.8 g/kg) and the carotid artery, jugular vein and trachea were cannulated. After baseline measurements the animals recei ved tabun, 60, 180 or 300 mu g/kg, and 2 min later the antidotes (all i.v.): obidoxime, HLo 7, or HI 6 (30 or 100 mu mol/kg, each) or atropi ne 10 mg/kg or a combination of atropine and one of the oximes. Respir atory and circulatory parameters were recorded for 60 min or until the death of the animal. Erythrocyte, brain and diaphragm AChE activity w as determined in every animal after the experiment. Poisoning by tabun resulted in a rapid deterioration of respiratory function and respira tory arrest within 5 min. Atropine treatment was very effective in imp roving the respiratory function after tabun 60 mu g/kg but was ineffec tive after tabun 300 mu g/kg. However, circulatory parameters were res tored almost completely in all atropine therapy groups. Therapy of tab un 300 mu g/kg poisoned animals with atropine plus oxime (30 mu mol/kg ) improved respiration to a variable extent and restored circulation. The efficacy decreased in the order obidoxime > HLo 7 > > HI 6. Use of oximes 100 mu mol/kg did not further increase the therapeutic effect. Grimes alone were completely ineffective. The considerable therapeuti c efficacy of atropine and oximes was not accompanied by a reactivatio n of diaphragm or brain AChE. Erythrocyte AChE was partially reactivat ed by obidoxime. Tabun primarily impaired central respiratory control but peripheral neuromuscular block developed already at low tabun dose s. Atropine was Very effective in restoring circulation but respiratio n was improved only after low doses of tabun. The results of this inve stigation demonstrate a considerable effect of atropine plus obidoxime or HLo 7 in improving respiration and circulation after high dose tab un. This effect was not accompanied by a noticeable AChE reactivation, indicating the involvement of some other ''direct'' mechanisms. HLo 7 has to be considered as a broad-spectrum antidote, being superior to obidoxime or HI 6.