Analysis of cardiovascular and respiratory effects of various doses of soman in guinea-pigs: efficacy of atropine treatment.
The acute cardiovascular and respiratory effects of poisoning by high soman doses and its therapy by atropine, as well as the underlying mechanisms, are not well known as yet. Therefore, it was the purpose of this study to analyze the circulatory and respiratory functions in soman-poisoned and atropine-treated guinea-pigs. Female Pirbright-white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the arteria carotis, vena jugularis and trachea were cannulated. After base line measurements, soman (32, 80 or 160 micrograms/kg, i.v.; i.e. 2, 5 or 10 x LD50, respectively) or saline were injected and 2 min later, atropine (10 mg/kg, i.v.) or saline were applied. Respiratory and circulatory parameters were recorded for 60 minutes or until death of the animals. Poisoning by soman resulted in a rapid respiratory arrest, followed by circulatory failure and death after a few minutes. Atropine treatment restored circulatory parameters after soman (2 x LD50) and improved respiration to about 80% of base line values. All animals survived the 60 minutes period. After soman (5 x LD50), atropine improved respiratory parameters only slightly and circulatory parameters markedly. Only 2 of the 8 guinea-pigs survived. Atropine was almost completely ineffective after soman (10 x LD50), despite of a transitory improvement of circulation, and all animals died within a few minutes. In control animals, atropine did not impair respiration or circulation. The results of this study suggest that the soman-induced respiratory depression is primarily caused at the central nervous level and that a significant peripheral neuromuscular block develops only at very high soman doses. The circulatory disturbances are mainly the result of bradycardia due to peripheral muscarinic stimulation. Atropine has a high therapeutic effect in the restoration of circulatory function and may even improve respiration at high soman doses.
Worek
F
F
Institute of Pharmacology and Toxicology, Federal Armed Forces Medical Academy, Garching, Germany.
Szinicz
L
L
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D005260:Female; D006168:Guinea Pigs; D012137:Respiratory System / Q000187:drug effects*; D012999:Soman / Q000037:antagonists & inhibitors / Q000506:poisoning*; D014520:Urethane / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D014520:Urethane; D001285:Atropine; D012999:Soman