Direct effects of phosphamidon on isolated working rat heart electrical and mechanical function

Phosphamidon (2-chloro-3-(diethylamino)-1-methyl-3-oxopropanyldimethyl phosphate) is widely used in agriculture as an organophosphate insecticide. It is a water-soluble cholinesterase inhibitor whose estimated rat LD50 is 9.2 mg/kg, ip. Mechanical and electrophysiologic direct effects of phosphamidon were studied in an isolated working rat heart model. Phosphamidon caused a positive inotropic effect, as indicated by increased maximum time derivative of left ventricular pressure and increased cardiac output. Stroke work and total pressure-volume area increased in a dose-dependent manner following perfusion with phosphamidon. Phosphamidon had in this preparation a biphasic effect on heart rate: at 10(-6) M concentration, heart rate increased, but at higher concentrations (10(-4)-10(-3) M) heart rate decreased significantly. High concentrations of phosphamidon caused a significant prolongation of the Q-T interval. We conclude that phosphamidon has potent cardiotoxic effects, both mechanical and electrophysiologic, on the isolated rat heart.