Arrhythmias in organophosphate poisoning: effect of atropine and bispyridinium oximes.
The effect of atropine and of the bispyridinium oximes, HI6 and HLö 7, on the electrocardiographic pattern was investigated in acutely nerve agent-poisoned guinea-pigs. The electrocardiographic, circulatory and respiratory parameters were recorded in female urethane-anaesthetized Pirbright-white guinea-pigs. After base line measurements, the animals received pyridostigmine (0.05 mumol/kg) and, 30 min later, tabun (5xLD50), sarin (5xLD50), soman (5xLD50 or 10xLD50) or VX (10xLD50 or 20xLD50), followed by saline or atropine (10 mg/kg) or atropine plus HI 6 or or HLö 7 (30 mumol/kg) 2 minutes later. Nerve agent poisoning resulted in respiratory arrest within 2-3 minutes, followed by circulatory arrest a few minutes later in nontreated animals. Antidote treatment rapidly restored heart rate and mean arterial pressure and improved the respiratory function to various extent. The nerve agent injection caused a marked sinus bradycardia and a subsequent complete atrioventricular block within 1-2 minutes, followed by idioventricular rhythm. No ventricular tachyarrhythmias were observed in these groups just before death. Atropine and atropine plus oxime administration immediately restored sinus rhythm which persisted in animals with sufficient respiration > 50% of base line) throughout the observation period (60 minutes). In guinea-pigs with depressed respiratory function ( < 50%), intermittent ST-T wave alterations and second degree atrioventricular block were observed. In some cases, especially in tabun and soman (10xLD50) poisoning, sinus rhythm converted to deleterious ventricular tachycardia within 1 minute after treatment. These results suggest that atropine-containing antidote combinations may induce lethal arrhythmias in nerve agent poisoning, which may be of clinical importance during intravenous treatment of severe inhalative intoxications.
Worek
F
F
Institut für Pharmakologie und Toxikologie, Sanitätsakademie der Bundeswehr, Garching, Germany.
Kleine
A
A
Falke
K
K
Szinicz
L
L
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D001285:Atropine / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D007928:Lethal Dose 50; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D062025:Organophosphate Poisoning; D010091:Oximes; D011725:Pyridines / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000627:therapeutic use; D015656:Respiratory Mechanics / Q000187:drug effects; D012999:Soman / Q000506:poisoning
D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; D001285:Atropine; D012999:Soman; C022870:asoxime chloride