title: Sarin causes autonomic imbalance and cardiomyopathy:  an important issue for military and civilian health.
abstract: Sarin, a lethal chemical nerve agent, may be a causative factor in multifactorial syndrome implicated in the Gulf War and Tokyo terrorist attacks. Although a high dose results in seizure and death, low-dose exposure may lead to autonomic imbalance and chronic cardiac pathologies. In this study, echocardiography and electrocardiography were used to examine the late-onset effects of a low-dose sarin on cardiac structure and function in mice. Adrenal corticosterone and tyrosine hydroxylase mRNA levels were measured. Stress responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis was also tested. Findings demonstrate changes consistent with a dilated cardiomyopathy, including left ventricular dilatation, reduced contractility, and altered electrophysiological and inotropic responses to β-adrenergic stimulation. Results also indicate reduced adrenal tyrosine hydroxylase mRNA, corticosterone and altered stress responsiveness of HPA indicating autonomic imbalance. The role of low-dose sarin/organophosphate exposure needs to be considered in the military and civilian populations that suffer from autonomic imbalance and/or cardiomyopathies of indeterminate origin.
authors.affiliation: Wright State University Boonshoft School Medicine, Dayton, OH 45435, USA.
authors.forename: Swapnil V
authors.initials: SV
authors.lastname: Shewale
authors.forename: Mark P
authors.initials: MP
authors.lastname: Anstadt
authors.forename: Michael
authors.initials: M
authors.lastname: Horenziak
authors.forename: Brent
authors.initials: B
authors.lastname: Izu
authors.forename: Eric E
authors.initials: EE
authors.lastname: Morgan
authors.forename: James B
authors.initials: JB
authors.lastname: Lucot
authors.forename: Mariana
authors.initials: M
authors.lastname: Morris
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D009202:Cardiomyopathies / Q000139:chemically induced*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003345:Corticosterone / Q000378:metabolism; D004452:Echocardiography; D004562:Electrocardiography; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010913:Pituitary-Adrenal System / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012524:Sarin / Q000633:toxicity*; D013312:Stress, Physiological; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002619:Chemical Warfare Agents; D012333:RNA, Messenger; D012524:Sarin; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone