Effect of pyridostigmine pretreatment on cardiorespiratory function in tabun poisoning.
1. The effect of pyridostigmine on cardiorespiratory function after oxime + atropine injection was investigated in tabun poisoned guinea-pigs and without tabun poisoning. 2. The trachea, a carotid artery and jugular vein were cannulated in female urethane-anaesthetised Pirbright-white guinea-pigs. After baseline measurements the animals received pyridostigmine (0.05 mumol kg-1) and 30 min later atropine (29.5 mumol kg-1) plus obidoxime, HI 6 or HLö 7 (30 or 100 mumol kg-1) or tabun (1.85 mumol kg-1 = 5 x LD50) followed by oxime + atropine treatment (all i.v.). Erythrocyte, brain and diaphragm acetylcholinesterase (AChE) activity were determined. Similar groups without pretreatment were included for comparison. 3. Pyridostigmine aggravated the oxime + atropine induced hypotension and prevented the increase in heart rate but not the respiratory stimulation. The pyridostigmine inhibited AChE recovered only in the 100 mumol kg-1 kg oxime groups at the end of the experiment. 4. In tabun poisoning, pyridostigmine reduced the oxime + atropine induced circulatory recovery and decreased the survival time and rate. It did not affect the therapeutic oxime + atropine effect on respiratory function. 5. These results suggest that pyridostigmine enhances oxime + atropine related circulatory depression which may be the reason for the reduced efficacy of oxime + atropine treatment in tabun poisoning. The possible mechanisms are discussed.
Worek
F
F
Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität, München, Germany.
Kleine
A
A
Szinicz
L
L
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D009768:Obidoxime Chloride / Q000494:pharmacology; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000008:administration & dosage* / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; D009768:Obidoxime Chloride; D001285:Atropine; C022870:asoxime chloride; D011729:Pyridostigmine Bromide; C009374:tabun