Further studies on the therapy of organophosphorous anti-cholinesterase intoxication with veratrinic compounds; the role of calcium

Experiments were carried out to investigate the role of calcium in the therapy of soman intoxication with 9-anthroic acid (ANCA), a compound with veratrine-like pharmacological properties. The effects of ANCA on the respiratory paralysis and on the calcium content of the blood and that of the hindleg muscles were determined in anaesthetized, atropinized rats injected with 4 times LD50 soman. The respiratory paralysis which in control animals occurs within a few min after the injection of soman can be delayed about 2.5 hr by treatment with ANCA. It was found that ANCA causes a small decrease of the blood calcium content, an effect which is potentiated by soman. A comparison was made between the calcium accumulation in the indirectly stimulated gastrocnemius-soleus muscles in these animals with that in the non-stimulated muscles on the other side. Whereas the injection of soman or ANCA alone caused no change, the combination of the two drugs induced a two-fold increase in the accumulation of calcium in the stimulated muscles. The non-stimulated muscles remained unaffected. The accumulation of calcium in the stimulated muscles induced by soman and ANCA could be partly antagonized by lowering the free calcium concentration of the blood by EDTA. Moreover, treatment with EDTA improved the therapeutic effects of ANCA. It is concluded that the therapy of soman poisoning with ANCA falls short in completely preventing respiratory failure since ANCA causes an accumulation of calcium in the stimulated muscles of soman-poisoned animals.