title: Central respiratory effects on motor nerve activities after organophosphate exposure in a working heart brainstem preparation of the rat.
abstract: The impact of organophosphorus compound (OP) intoxication on the activity of central respiratory circuitry, causing acetylcholinesterase (AChE) inhibition and accumulation of acetylcholine in the respiratory brainstem circuits, is not understood. We investigated the central effect of the OP Crotylsarin (CRS) on respiratory network activity using the working heart brainstem preparation, which specifically allows for the analysis of central drug effects without changes in brainstem oxygenation possibly caused by drug effects on peripheral cardio-respiratory activity. Respiratory network activity was determined from phrenic and hypoglossal or vagal nerve activities (PNA, HNA, VNA). To investigate combined central and peripheral CRS effects hypo-perfusion was used mimicking additional peripheral cardiovascular collapse. Systemic CRS application induced a brief central apnea and complete AChE-inhibition in the brainstem. Subsequently, respiration was characterised by highly significant reduced PNA minute activity, while HNA showed expiratory related extra bursting indicative for activation of un-specified oro-pharyngeal behaviour. During hypo-perfusion CRS induced significantly prolonged apnoea. In all experiments respiratory activity fully recovered after 1h. We conclude that CRS mediated AChE inhibition causes only transient central breathing disturbance. Apparently intrinsic brainstem mechanisms can compensate for cholinergic over activation. Nevertheless, combination of hypo-perfusion and CRS exposure evoke the characteristic breathing arrests associated with OP poisoning.
authors.affiliation: Dept. of Neurophysiology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany. tanja.klein@helmholtz-muenchen.de
authors.forename: Tanja
authors.initials: T
authors.lastname: Klein-Rodewald
authors.forename: Thomas
authors.initials: T
authors.lastname: Seeger
authors.forename: Mathias
authors.initials: M
authors.lastname: Dutschmann
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.forename: Michael
authors.initials: M
authors.lastname: Mörschel
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001237:Asphyxia / Q000503:physiopathology; D001933:Brain Stem / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D010525:Peripheral Nerves / Q000187:drug effects* / Q000502:physiology; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012132:Respiratory Muscles / Q000187:drug effects / Q000294:innervation*; D056152:Respiratory Rate / Q000187:drug effects* / Q000502:physiology; D012524:Sarin / Q000031:analogs & derivatives* / Q000633:toxicity; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: C071511:crotylsarin; D012524:Sarin; D000110:Acetylcholinesterase