Sodium cyanate: From a promising therapeutic agent to a research tool in high altitude physiology

Sodium cyanate (NaOCN) first appeared on the biomedical scene as a potential therapeutic agent for sickle-cell disease. Although it did not fulfil its early promise in the clinic, it proved to be useful as a pharmacological tool in physiological research, particularly in the physiology of oxygen transport. NaOCN has been especially valuable in the area of investigation which is reviewed here: the study of oxygen transport, both in normoxic and in hypoxic conditions, in experimental models in which NaOCN was used to induce a shift to the left of the oxygen dissociation curve. The classical idea is that a low Hb-O₂ affinity is of adaptive value for life at high altitudes but it has been challenged by several pieces of evidence. One of them is the demonstration of increased survival in hypoxic hypoxia of animals with a high Hb-O₂ affinity induced by NaOCN. We also discuss the advantages and potentially confounding factors which should be taken into consideration when interpreting results of studies in which the oxygen dissociation curve has been modified by administration of NaOCN.