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

Abstract

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.