Investigation of the pathogenesis caused by exposure to varying doses of VX nerve agent in rat with special reference to cardiotoxicity

Abstract

Cardiotoxicity was investigated in rats challenged with nerve agent VX, S-(2-diisopropylaminoethyl)-O-ethylmethyl phosphonothiolate (acute 1.6 LD50 and 1 LD50; and chronic 0.4 LD50). Histologic examination of various organs revealed that VX produced characteristic cardiac lesions while morphological changes in other organs were minimal. Myocardial damage consisted of mononuclear cellular infiltration, myofibre degeneration and necrosis. Electrocardiography recordings showed QT interval prolongations and abnormalities in cardiac rhythm (atrioventricular blocks, arrhythmias and a??Torsade de pointea??) in the intoxicated rats. Arrhythmias were detected up to day 14 post 1 LD50 exposure. In the chronic 0.4 LD50 VX group, cardiac arrhythmias appeared as early as the second day of dosing, before manifestation of specific clinical symptoms of poisoning. The abberations in cardiac rhythm were reproducible up to five days after the last dosing day. This is a novel finding in the research of cardiac toxicity of nerve agents.