The Effect of Carbon Monoxide on the Oxyhemoglobin Dissociation Curve

J. B. S. Haldane (13) was the first to study theoretically the equilibrium between hemoglobin and mixtures of 02 and CO which were of insufficient concentration to saturate the hemoglobin completely. His treatment was subsequently amplified and modified by A. V. Hill (15), Stadie and Martin (23), Barcroft (4), and Peters and Van Slyke (19). As a result of this work it has been generally accepted that partial saturation of the blood hemoglobin with CO shifts the oxygen dissociation curve of the remaining hemoglobin progressively to the left, and also makes the curve less S-shaped and more hyperbolic’ (“Haldane effect”). This indicates that the blood in vivo, if partially saturated with CO, must cling to its O2 with greater tenacity so that the tissues have much more difficulty in obtaining O2 from the blood than they do when the OgHb of the blood is reduced to a corresponding extent by anemia. This deduction has been used by Haldane to explain why “Miners may do their ordinary work though their hemoglobin percentage is reduced to half by ankylostomiasis-whereas a person whose blood is half saturated with CO is practically helpless.” A somewhat puzzling and paradoxical feature of CO-poisoning which has been explained by the Haldane effect is that with mice at very low ~0, the addition of a tlrace of CO to the inspired air may actually help the organism to acquire OZ. Haldane’s original theory was only tested experimentally by observations on the CO-dissociation curve of hemoglobin when part of the hemoglobin was combined with 0,; parallel observations as to the effect of partial combination of the hemoglobin with CO on the 02 dissociation curve of the remaining hemoglobin were not available until the work of Stadie and Martin twelve years later. These authors considered that their hypothesis was well thought0 was excellent agreement between theory Stadie in a recent conversation has, however, present opinion the agreement was not as good permitted us to say as could be desired, that partic supported by what they and experiment. Doctor in his ularly as the observations were limited to a somewhat narrow portion of the dissociation curve. Since the subject is of interest, alike in the theory of the hemoglobin reactions and in the practical study of the effects of CO poisoning both at sea level and high altitudes, we have thought it desirable to reinvestigate the subject in a more complete fashion. In so doing we have been led to some profitable simplifications in the development of the theory. It is satisfactory to find that the original