title: Multiple exposures to sarin vapor result in parasympathetic dysfunction in the eye but not the heart.
abstract: Several studies in conscious animals have reported parasympathetic dysfunction in the eyes following exposure to cholinesterase inhibitors. Given the similarities between the autonomic innervation in the eye and the heart, it is possible that parasympathetic dysfunction could also occur in the heart. Therefore, the present study assessed time domain indices of heart rate variability in conscious rats surgically implanted with telemetric transmitters to investigate the hypothesis that multiple exposures to the nerve agent sarin would result in muscarinic receptor desensitization and parasympathetic dysfunction in the heart. Animals exposed to sarin vapor on multiple occasions developed parasympathetic dysfunction in the eye characterized by an attenuated response to light and a diminished miotic response to sarin vapor exposure. However, the same dose of sarin vapor failed to produce any effects on either time domain indices of HRV or the magnitude of the tachycardia induced by atropine, suggesting that autonomic control in the heart was not affected. It is possible that the dose of sarin used in the present study was insufficient to inhibit cardiac acetylcholinesterase (AChE). Additional studies utilizing higher doses of sarin may be able to inhibit cardiac AChE, producing overstimulation of cardiac muscarinic receptors, ultimately resulting in desensitization and parasympathetic dysfunction.
authors.affiliation: Operational Toxicology Team, U.S. Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, Maryland 21010, USA. paul.a.dabisch@us.army.mil
authors.forename: Paul A
authors.initials: PA
authors.lastname: Dabisch
authors.forename: Filip
authors.initials: F
authors.lastname: To
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Kerut
authors.forename: Michael S
authors.initials: MS
authors.lastname: Horsmon
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mioduszewski
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D015716:Electrocardiography, Ambulatory / Q000187:drug effects; D005123:Eye / Q000187:drug effects / Q000294:innervation* / Q000473:pathology; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D019570:Inhalation Exposure; D008297:Male; D015877:Miosis; D009206:Myocardium / Q000201:enzymology; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic; D012025:Reflex, Pupillary / Q000187:drug effects; D012524:Sarin / Q000633:toxicity*; D014835:Volatilization
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; D012524:Sarin; D002802:Cholinesterases