Ferrihaemoglobin formation by amyl nitrite and sodium nitrite in different species in vivo and in vitro.

The ferrihaemoglobin (HbFe3+) formation by amyl nitrite (AN) or sodium nitrite (NaNO2) was studied in different species including man, in vivo and in vitro. In in vivo studies AN was administered intravenously (i.v.), intramuscularly (i.m.), by inhalation, or orally. NaNO2 was injected i.v.. AN i.v. produced HbFe3+ much more rapidly than NaNO2 in dogs, cats, rabbits, and rats. In dogs, i.m. injection of AN was followed by a very slow linear increase in the HbFe3+ content. Inhalation of AN did not lead to HbFe3+ formation in dogs unless it was rebreathed in a closed (bag) or not completely open (gas mask) system. HbFe3+ was produced by oral AN in dogs, the effect being enhanced by addition of DMSO. Inhalation of AN by human volunteers in a gas mask and from ampoules crushed close to the nose did not induce haemoglobin oxidation to a practically significant extent, but it was associated with headache, tiredness, dizziness, and a fall in blood pressure. In in vitro studies, in contrast to NaNO2, AN produced HbFe3+ instantaneously in erythrocytes of various species and in purified human haemoglobin. AN 1 mol yielded 2 mol Fe3+. Only 20% of the oxygen released during the oxidation of haemoglobin by AN or NaNO2 was recovered. In 0.2 M phosphate buffer, pH 7.4, 0.01 mol O2/mol AN was consumed. CO2 was released in the presence of AN, but not of NaNO2, from blood, plasma, and 0.02 M NaHCO3 solution. The ratio (lactate)/(pyruvate) decreased when HbFe3+ was formed by AN or NaNO2.