Citation

Shewale SV, Anstadt MP, Horenziak M, Izu B, Morgan EE, Lucot JB, Morris M. J. Cardiovasc. Pharmacol. 2012; 60(1): 76-87.

Affiliation

1Wright State University Boonshoft School Medicine, Dayton, OH 2Air Force Institute of Technology, Dayton, OH 3University of Toledo College of Medicine, Toledo, OH.

Copyright

(Copyright © 2012, Lippincott Williams and Wilkins)

DOI

10.1097/FJC.0b013e3182580b75

PMID

22549449

Abstract

Sarin, a lethal chemical nerve agent, may be a causative factor in multifactorial syndrome implicated in the Gulf War and Tokyo terrorist attacks. While high dose results in seizure and death, low dose exposure may lead to autonomic imbalance and chronic cardiac pathologies. In the present 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 (TH) 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 TH mRNA, corticosterone and altered stress responsiveness of HPA indicating autonomic imbalance. The role of low-dose sarin/organophosphate exposure needs to be considered in military and civilian population who suffer from autonomic imbalance and/or cardiomyopathies of indeterminate origin.

Language: en