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Ben-Ami H, Ben-Haim SA, Edoute Y, Hayam G, Taitelman U: Direct effects of phosphamidon on isolated working rat heart electrical and mechanical function. Toxicol Appl Pharmacol. 1991 Sep 15;110(3):429-34.
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. |
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