Sarin causes autonomic imbalance and cardiomyopathy: an important issue for military and civilian health

J Cardiovasc Pharmacol. 2012 Jul;60(1):76-87. doi: 10.1097/FJC.0b013e3182580b75.

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.

MeSH terms

  • Adrenal Glands / metabolism
  • Animals
  • Autonomic Nervous System / drug effects*
  • Autonomic Nervous System / physiopathology
  • Cardiomyopathies / chemically induced*
  • Chemical Warfare Agents / toxicity*
  • Corticosterone / metabolism
  • Echocardiography
  • Electrocardiography
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pituitary-Adrenal System / metabolism
  • RNA, Messenger / metabolism
  • Sarin / toxicity*
  • Stress, Physiological
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Chemical Warfare Agents
  • RNA, Messenger
  • Sarin
  • Tyrosine 3-Monooxygenase
  • Corticosterone