title: Percutaneous exposure to VX: clinical signs, effects on brain acetylcholine levels and EEG.
abstract: The nerve agent VX has a variable and delayed absorption through the skin, which may have implications for treatment regimens. In the present study, central and peripheral effects of percutaneous VX intoxication were investigated in hairless guinea pigs. Although onset times of clinical signs varied considerably, the relative onset times of signs of poisoning were shown to have a predictive value for survival time. All animals showed elevation of brain choline (Ch) levels. Only two of six animals demonstrated seizure activity on EEG, which was accompanied by acetylcholine (ACh) accumulation. The non-seizing animals displayed only marginal increases of ACh levels, but significant changes in all EEG bands. Acetylcholinesterase activity was highly inhibited in brain and diaphragm. The increases in Ch levels and EEG effects observed in non-seizing animals probably reflected those of ischemia induced by peripheral effects leading to cardiorespiratory compromise. In conclusion, clinical signs will mainly serve as indicators for the onset and maintenance of treatment in subsequent studies.
authors.affiliation: Department Diagnosis and Therapy, TNO Defence, Security and Safety, BU Biological and Chemical Protection, PO Box 45, Lange Kleiweg 137, 2280 AA Rijswijk, The Netherlands.
authors.forename: Marloes J A
authors.initials: MJ
authors.lastname: Joosen
authors.forename: Marcel J
authors.initials: MJ
authors.lastname: van der Schans
authors.forename: Herman P M
authors.initials: HP
authors.lastname: van Helden
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004569:Electroencephalography; D006168:Guinea Pigs; D008297:Male; D017551:Microdialysis; D009946:Organothiophosphorus Compounds / Q000633:toxicity*
chemical_list: D000109:Acetylcholine; D009946:Organothiophosphorus Compounds; C009680:VX-agent