QT Prolongation as an Isolated Long-Term Cardiac Manifestation of Dichlorvos Organophosphate Poisoning in Rats.

Abstract

Organophosphates (OP) are used extensively as pesticides and as chemical weapons. Cardiotoxicity is a major concern in survivors of the acute poisoning. To characterize the delayed cardiac effects of OP, rats were poisoned by intraperitoneal administration of dichlorvos. In group I, poisoning (0.25-, 0.75-, 1.4-LD50) was followed by application of atropine and obidoxime. In group II, poisoning (0.35-, 0.5-LD50) was done without antidotes. Cardiac evaluation included electrocardiography and echocardiography 2- and 6-week post-exposure, arrhythmia susceptibility following administration of Isoproterenol (150 mcg/kg), and histological evaluation. All poisoned animals displayed cholinergic symptoms. In group I, all animals exposed to 1.4-LD50 (n = 3) had profound convulsions and died despite antidote treatment. However, in the lower doses, all animals survived and no cardiac abnormalities were noted during follow-up. In group II, six animals had convulsions and died. Surviving animals had mild but significant prolongation of corrected QT at both 2 and 6 weeks, compared to shams. There were no notable echocardiographic, gravimetric, or histological differences between poisoned and sham animals. Our data indicate that dichlorvos poisoning is associated with QT prolongation without anatomical or histopathological abnormalities. This new model can be used to elaborate the molecular mechanism\s of QT prolongation following OP poisoning.

• Authors: Arthur Shiyovich, Ran Matot, Sigal Elyagon, Noah Liel-Cohen, Yossi Rosman, Shai Shrot, Michael Kassirer, Amos Katz, Yoram Etzion
• Journal: Cardiovascular toxicology (Cardiovasc Toxicol) Vol. 18 Issue 1 Pg. 24-32 (02 2018) ISSN: 1559-0259 [Electronic] United States
• PMID: 28510081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antidotes
• Obidoxime Chloride
• Atropine
• Dichlorvos

Topics

• Action Potentials (drug effects)
• Animals
• Antidotes (pharmacology)
• Atropine (pharmacology)
• Cardiotoxicity
• Dichlorvos
• Disease Models, Animal
• Heart Conduction System (drug effects, physiopathology)
• Heart Rate (drug effects)
• Long QT Syndrome (chemically induced, drug therapy, physiopathology)
• Male
• Obidoxime Chloride (pharmacology)
• Organophosphate Poisoning (drug therapy, etiology, physiopathology)
• Rats, Sprague-Dawley
• Time Factors