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.
Ben-Ami
H
H
Cardiovascular Research Group, Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
Ben-Haim
S A
SA
Edoute
Y
Y
Hayam
G
G
Taitelman
U
U
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D010707:Phosphamidon / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains
D010707:Phosphamidon