Sarin Causes Autonomic Imbalance and Cardiomyopathy

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.

Ouabain prevents pathological cardiac hypertrophy and heart failure through activation of phosphoinositide 3-kinase α in mouse

“…Left ventricular function and geometry was assessed as previously described [ 36 ]. Briefly, mice underwent echocardiographic assessment using an ACUSON Sequoia ™ C512 Ultrasound System (Siemens) with a 15-MHz linear array transducer.…”

Acetylcholinesterase inhibitor exposures as an initiating factor in the development of Gulf War Illness, a chronic neuroimmune disorder in deployed veterans

“…A few of these studies have investigated the potential outcomes of low-dose, sub-lethal exposure(s) to sarin or sarin surrogates alone in relationship to GWI symptomology. While subclinical inhalation of sarin has been demonstrated to be capable of producing signs of immunosuppression, such as reduced T-cell responses and reduced corticosterone levels ( Henderson et al, 2001 ; Kalra et al, 2002 ), as well as autonomic imbalance and cardiomyopathy ( Shewale et al, 2012 ), these studies do not directly correlate with the neuroimmune dysfunction hypothesis for GWI. However, repeated, low-dose exposure to the sarin surrogate diisopropyl fluorophosphate (DFP) has been shown to instigate depression, cognitive impairment, and neuronal damage ( Phillips and Deshpande, 2016 , 2018 ).…”

Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review

“…The long term decrease in both serum corticosterone and plasma adrenocorticotropic levels indicates that hypothalamus–pituitary–adrenal axis suppression likely occurred due to sarin exposure, although the mechanism of action is not entirely clear (Peña-Philippides et al 2007). Shewale et al (2012) also demonstrated altered HPA responsiveness and reduced corticosterone levels following sarin exposure and postulates that the cause of this alteration was an autonomic imbalance.…”