Effect of phosphamidon and obidoxime on the QT-RR relationship of isolated rat heart.
We studied the effects of phosphamidon (an organophosphate compound), obidoxime (a cholinesterase reactivator), and their combination, phosphamidon/obidoxime (PD/OB) on cardiac cycle length (RR), QT interval, and on QT-RR relationship of isolated rat heart. Cardiac cycle length did not change significantly following perfusion with phosphamidon or obidoxime alone; however, following perfusion with PD/OB, RR significantly increased at high concentrations (10(-3) M) of both drugs. The QT interval lengthened by 5% following perfusion with phosphamidon, did not change following perfusion with obidoxime, and increased by 10% following perfusion with PD/OB. The QT-RR relationship without drugs was positive and linear. Following perfusion with phosphamidon alone, the slope of the relationship decreased significantly, while perfusion with obidoxime alone did not change the QT-RR relationship. Perfusion with PD/OB at low concentrations decreased the slope of the relationship; however, at the highest concentration (10(-3) M) the QT-RR relationship was inverted and became negative. Ventricular arrhythmias as premature ventricular beats, or bigeminies, were noted with increasing frequency following perfusion with increasing doses of phosphamidon. Perfusion with obidoxime did not cause arrhythmias, whereas perfusion with PD/OB caused premature ventricular beats, bigeminies, and ventricular tachycardias at high doses. We suggest that obidoxime modulates the direct effects of phosphamidon on the cardiac repolarization process. PD/OB at high concentrations invert the normal depolarization-repolarization coupling and may therefore potentiate arrhythmias.
Ben-Haim
S A
SA
Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa.
Ben-Ami
H
H
Hayam
G
G
Taitelman
U
U
Edoute
Y
Y
D000818:Animals; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009768:Obidoxime Chloride / Q000494:pharmacology*; D010477:Perfusion; D010707:Phosphamidon / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology
D010707:Phosphamidon; D009768:Obidoxime Chloride