QTc prolongation and cardiac lesions following acute organophosphate poisoning in rats.
Sarin and soman induced the following similar effects: prolongation of QT interval duration, cardiac lesions and immediate and statistically significant decrease in body weight. However, animals exposed to soman remained underweight and suffered delayed death. Thus, as sarin produced both cardiac lesions and QT prolongation, without exhibiting late death, it is unlikely that the late death observed in soman-poisoned rats are attributable to QT prolongation and the occurrence of life-threatening arrhythmias. It is postulated that low body weight may precipitate late mortality in soman-exposed rats. It is well documented that QT prolongation in the rat is explained in terms of blockade of the Ito potassium channels and the Na+/Ca+2 exchanger. Soman and sarin may exert their effect on QT interval duration through non-specific action on these sites. As drug-induced QT prolongation in man is mediated by blockade of Ikr potassium channels, the data presented in this study may not predict late death in humans in cases of organophosphate intoxication.
Abraham
S
S
Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 70450, Israel.
Oz
N
N
Sahar
R
R
Kadar
T
T
D000208:Acute Disease; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D004562:Electrocardiography / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D062025:Organophosphate Poisoning; D051381:Rats; D017207:Rats, Sprague-Dawley; D012524:Sarin / Q000506:poisoning*; D012999:Soman / Q000506:poisoning*
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D012999:Soman; D012524:Sarin