Some physiological and pathological effects of moderate carbon monoxide exposure.

The toxic effect of carbon monoxide on the animal organism has probably been known by man since the discovery of fire, and we know it was recognized as a dangerous poison in ancient times. It was Claude Bernard who first studied its mode of action, and he showed that blood treated with carbon monoxide was unable to bind oxygen. J. S. Haldane (1895) is considered as the pioneering investigator of the physiology and toxicology of carbon monoxide. Together with some of his co-workers he performed the now classical studies on the effects on man of carbon monoxide exposure, and his first paper appeared in 1895. Haldane thought, as a result of his investigations, that the only toxic effect of carbon monoxide was its ability to bind to haemoglobin at a much higher degree than oxygen, thus displacing oxygen in oxyhaemoglobin and depriving blood of its oxygen transport ability. This conclusion was derived from the fact that animals such as mice could live for days with their haemoglobin completely bound to carbon monoxide if the dissolved oxygen in plasma was increased sufficiently by placing the mice in a high pressure chamber. As students we learnt that these and other classical carbon monoxide studies gave valuable information about normal physiological mechanisms concerning oxygen uptake by the blood and its release. Medical interest in carbon monoxide, however, was dominated by its toxic and dangerous effects