title: Mechanisms of respiratory failure produced by neostigmine and diisopropyl fluorophosphate.
abstract: Acetylcholinesterase inhibitors produce diverse physiologic effects, but lethal exposure consistently produces respiratory failure due to neuromuscular paralysis or depression of respiratory control centers in the medulla. Simultaneous measurement of gastrocnemius muscle contraction and efferent phrenic nerve activity was used to determine the primary cause of respiratory failure produced by neostigmine and diisopropyl fluorophosphate (DFP) in anesthetized cats. Both neostigmine and DFP abolished phrenic nerve activity prior to producing neuromuscular blockade. Furthermore, neostigmine did not alter brain acetylcholinesterase activity and pretreatment with either atropine methylbromide or atropine increased the dose of neostigmine required to abolish phrenic nerve activity. In contrast, DFP abolished brain cholinesterase activity and only atropine inhibited its respiratory effects. Despite the loss of efferent phrenic nerve activity, there is no evidence of a direct effect of neostigmine on respiratory control centers. Neostigmine may instead alter afferent inputs which modulate respiration to produce a reflex respiratory failure.
authors.affiliation: Department of Anesthesia, Georgetown University School of Medicine, Washington, DC 20007.
authors.forename: N W
authors.initials: NW
authors.lastname: Fleming
authors.forename: T R
authors.initials: TR
authors.lastname: Henderson
authors.forename: K L
authors.initials: KL
authors.lastname: Dretchen
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002415:Cats; D002800:Cholinesterase Inhibitors; D005260:Female; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000009:adverse effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009388:Neostigmine / Q000009:adverse effects*; D010791:Phrenic Nerve / Q000187:drug effects; D012131:Respiratory Insufficiency / Q000139:chemically induced*
chemical_list: D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; D009388:Neostigmine; D001285:Atropine