Effects of 2-pyridinium aldoxine methochloride and atropine in relation to elevation of blood pH in soman-poisoned dogs

Abstract

The effects of various chemical treatments on the respiratory and cardiovascular deficits caused by poisoning dogs with pinacolyl methylphosphonofluoridate (soman) and on survival of the dogs were studied. A comparison was made between treatment of the poisoned dogs with atropine alone and with atropine plus 2-pyridinium aldoxime methochloride (PAM). Intravenous injection of 1 mg/kg of atropine and 104 mg/kg of PAM within 2 min after poisoning dogs with 30 μg/kg of soman i.v. (approximately 3 times the ld50) counteracted the respiratory and cardiovascular collapse produced by soman and saved 12 of 13 animals. Phenoxybenzamine, 0.5 mg/kg, injected i.v. immediately after the onset of hypertension resulting from treatment of soman-poisoned dogs with atropine and PAM affected a more rapid return to normal blood pressure levels without impairing survival. The half-time for loss of reactivatability of soman-inhibited red blood cell acetylcholinesterase (RBC (AChE) in vivo was 5.55 min at pH 7.4 and 12.50 min at pH 7.8 (achieved by pretreatment of the dogs with Tris buffer. At the higher pH, administration of PAM could be delayed for 20 min after poisoning with 50 μg/kg of soman, and 23.4 per cent of the inhibited RBC ChE was reactivated and 80 per cent of the dogs were saved. When the blood was at physiological pH, dogs poisoned with soman and given PAM 20 min later showed little or no recovery of inhibited RBC AChE and complete mortality.