Evaluation of reactivation test in anaesthetized dogs with experimental intoxication with nerve agents.
Following repeated antidotal treatment of anaesthetized dogs (1 min with atropine, 10 min with atropine and obidoxime, 60 min with atropine and obidoxime) after the intoxication with soman, sarin and VX (1 x LD50, i.m.), the blood cholinesterases (erythrocyte, whole blood, plasma) were monitored and their reactivatability (whole blood) was determined. During this treatment, the activities of erythrocyte acetylcholinesterase (AChE), plasma butyrylcholinesterase (BuChE) and whole blood cholinesterases were monitored. Atropine and obidoxime did not affect cholinesterase activities in control animals, whereas administration of obidoxime to dogs intoxicated with nerve agent caused an increase in the cholinesterase activities. The sensitivity of cholinesterases decreased in the order erythrocyte AChE > whole blood cholinesterases > plasma BuChE, respectively. Following sarin intoxication, blood cholinesterases were increased after the obidoxime administration. Intoxication with VX showed a similar picture but reactivation after the obidoxime administration was greater. In soman intoxication, the picture of cholinesterase changes was similar during the first 30 min of treatment. Then the increase in AChE activity following obidoxime administration was not as high as in the case of sarin and VX intoxication. Thus, the reactivation efficacy of obidoxime during nerve agent intoxication indicates that its repeated administration could be easily monitored using the reactivation test.
Bajgar
J
J
Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Fusek
J
J
Bartosova
L
L
Jun
D
D
Kuca
K
K
D000110:Acetylcholinesterase / Q000097:blood; D000758:Anesthesia; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use; D002091:Butyrylcholinesterase / Q000097:blood; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D009768:Obidoxime Chloride / Q000627:therapeutic use; D009946:Organothiophosphorus Compounds / Q000506:poisoning; D011041:Poisoning / Q000097:blood / Q000188:drug therapy*; D012524:Sarin / Q000506:poisoning; D012999:Soman / Q000506:poisoning
D000110:Acetylcholinesterase; D000931:Antidotes; D001285:Atropine; D002091:Butyrylcholinesterase; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009768:Obidoxime Chloride; D009946:Organothiophosphorus Compounds; D012524:Sarin; D012999:Soman; C009680:VX-agent