Acute and subacute organophosphate poisoning in the rat.
The intermediate syndrome in organophosphate poisoning is clinically characterized by weakness in the territory of cranial nerves, weakness of respiratory, neck and proximal limb muscles, and depressed deep tendon reflexes. It occurs between the acute cholinergic crisis and the usual onset of organophosphate-induced delayed neurotoxicity. The weakness has been ascribed to muscle fiber necrosis. Fenthion has been the most common cause. This study assesses the occurrence of the necrotizing myopathy in rats in relation to the clinical course and the acetylcholinesterase (AChE) inhibition after poisoning with organophosphates representative for each of the major types of organophosphate-related neurotoxicity. Marked differences are noted in the duration of cholinergic symptoms and of AChE inhibition after either paraoxon and mipafox, or fenthion poisoning. The necrotizing myopathy begins shortly after the initial decline in AChE activity with all organophosphates studied. Maximal muscle involvement occurs within the first 2 days of the poisoning with all organophosphates studied. The myopathy is not aggravated by a further decline in AChE activity in fenthion poisoning. Our data argues against the monophasic necrotizing myopathy being the cause of the intermediate syndrome, and is suggestive of persistent AChE inhibition being involved.
De Bleecker
J
J
Neurology Department, University Hospital, Gent, Belgium.
Lison
D
D
Van Den Abeele
K
K
Willems
J
J
De Reuck
J
J
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D005284:Fenthion / Q000506:poisoning; D007306:Insecticides / Q000506:poisoning*; D007531:Isoflurophate / Q000031:analogs & derivatives / Q000506:poisoning; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D010261:Paraoxon / Q000506:poisoning; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D007531:Isoflurophate; C005238:mipafox; D005284:Fenthion; D010261:Paraoxon