ANALYSIS OF CARDIOVASCULAR AND RESPIRATORY EFFECTS OF VARIOUS DOSES OF SOMAN IN GUINEA-PIGS - EFFICACY OF ATROPINE TREATMENT

Authors
Citation
F. Worek et L. Szinicz, ANALYSIS OF CARDIOVASCULAR AND RESPIRATORY EFFECTS OF VARIOUS DOSES OF SOMAN IN GUINEA-PIGS - EFFICACY OF ATROPINE TREATMENT, Archives internationales de pharmacodynamie et de therapie, 325, 1993, pp. 96-112
Citations number
36
Categorie Soggetti
Chemistry,"Pharmacology & Pharmacy
ISSN journal
00039780
Volume
325
Year of publication
1993
Pages
96 - 112
Database
ISI
SICI code
0003-9780(1993)325:<96:AOCARE>2.0.ZU;2-1
Abstract
The acute cardiovascular and respiratory effects of poisoning by high soman doses and its therapy by atropine, as well as the underlying mec hanisms, are not well known as yet. Therefore, it was the purpose of t his study to analyze the circulatory and respiratory functions in soma n-poisoned and atropine-treated guinea-pigs. Female Pirbright-white gu inea-pigs were anaesthetized with urethane (1.8 g/kg) and the arteria carotis, vena jugularis and trachea were cannulated. After base line m easurements, soman (32, 80 or 160 mug/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 param eters were recorded for 60 minutes or until death of the animals. Pois oning by soman resulted in a rapid respiratory arrest, followed by cir culatory failure and death after a few minutes. Atropine treatment res tored circulatory parameters after soman (2 x LD50) and improved respi ration 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 o f the 8 guinea-pigs survived. Atropine was almost completely ineffecti ve after soman (10 x LD50), despite of a transitory improvement of cir culation, and all animals died within a few minutes. In control animal s, atropine did not impair respiration or circulation. The results of this study suggest that the soman-induced respiratory depression is pr imarily caused at the central nervous level and that a significant per ipheral neuromuscular block develops only at very high soman doses. Th e circulatory disturbances are mainly the result of bradycardia due to peripheral muscarinic stimulation. Atropine has a high therapeutic ef fect in the restoration of circulatory function and may even improve r espiration at high soman doses.