Low Dose Sarin (0.4 LD 50) Causes Delayed Cardiac Remodeling and Reduces Left Ventricular Function

Abstract

<p>It has been reported that low dose Sarin (an organophosphate agent that acts by irreversibly binding to acetyl cholinesterase) is associated with long-term pathology in the brain and heart; however, the effects of Sarin on the cardiovascular system are not yet well-defined. Sarin has been implicated as an etiological agent in Gulf War Illness; thus, the role of Sarin in producing long term illness has important military implications. This study used Echocardiography (for determining the structure and function of the LV), Electrocardiography, and histology to determine Sarin's effect on the murine cardiovascular system. C57BL/6J mice were injected with either Sarin 0.4 LD 40 or saline on two consecutive days and studied for 10 weeks after exposure. In the Sarin animals, measurements showed a marked increase of the heart-to-body-weight ratio (p = 0.026) and a significant decrease in the size of the left ventricular lumen (p = 0.0014). Cardiomyocytes were significantly larger in the Sarin mice (p = 0.025), and atrial and brain natriuretic peptide levels were increased (p = 0.028 and 0.010, respectively). Analysis of the electrocardiograms showed significant ST/Twave changes in the Sarin groups (p = 0.0015 and 0.032, respectively). Similarly, Echocardiography showed altered structure (End Systolic and Diastolic Areas) and significantly decreased performance (Ejection Fraction) of the left ventricle in the Sarin animals at 10 week time point. This study indicates that Sarin plays a role in cardiac remodeling and the reduction of cardiac performance.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>