Isoamyl nitrite has previously been considered acceptable as an inhaled
cyanide antidote; therefore, the antidotal utility of this organic
nitrite compared with
sodium nitrite was investigated. To facilitate a quantitative comparison, doses of both
sodium nitrite and
isoamyl nitrite were given intraperitoneally in equimolar amounts to sublethally
cyanide-challenged mice. Righting recovery from the knockdown state was clearly compromised in the
isoamyl nitrite-treated animals, the effect being attributable to the toxicity of the isoamyl alchol produced during hydrolysis of the
isoamyl nitrite to release
nitrite anion. Subsequently, inhaled aqueous
sodium nitrite aerosol was demonstrated to ameliorate sublethal
cyanide toxicity, when provided to mice after the toxic dose, by the more rapid recovery of righting ability compared to that of the control animals given only the toxicant. Aerosolized
sodium nitrite has thus been shown by these experiments to have promise as a better alternative to organic
nitrites for development as an inhaled
cyanide antidote. The inhaled
sodium nitrite led to the production of NO in the bloodstream as determined by the appearance of EPR signals attributable to
nitrosylhemoglobin and
methemoglobin. The
aerosol delivery was performed in an unmetered inhalation chamber, and in this study, no attempt was made to optimize the procedure. It is argued that administration of an effective inhaled aqueous
sodium nitrite dose in humans is possible, though just beyond the capability of current individual
metered-dose inhaler designs, such as those used for
asthma. Finally, working at slightly greater than LD50 NaCN doses, it was fortuitously discovered that (i)
anesthesia leads to significantly prolonged survival compared to that of unanesthetized animals and that (ii) the antidotal activity of
nitrite anion was completely abolished under
anesthesia. Plausible explanations for these effects in mice and their practical consequences in relation to testing putative
cyanide antidotes are discussed.