Oxygenation and Oxidation 



Several participants in this Conference (J. Wyman, L. C. Pauling 

 and F. J. W. Roughton) deal with the oxygen dissociation curve of 

 haemoglobin. It seems that expert tailoring is still required to fit well 

 the garment of theory to the peculiar shape of the experimentally 

 obtained curve, and the concern has been both here and in the past 13 

 to supply fitting explanations, consonant with advancing knowledge 

 of molecular structure, to the experimental data. I do not wish to imply 

 that this objective is not important. It is. But our concern has been 

 with the value of the measurements themselves, with the securing of 

 accurate points from which the curve is constructed, and especially 

 with obtaining reliably the necessary data in vivo, rather than as in 

 most past work upon blood or haemoglobin solutions equilibrated 

 in vitro. 



Definitions and Methods 



Statement of the problem — The construction of an oxygen dissociation 

 curve requires information upon at least two quantities, percentage 

 oxygen saturation and oxygen partial pressure, p0 2 . In the past the 

 problem was simplified. A blood sample was equilibrated in a tono- 

 meter with gas mixtures of varying composition of oxygen and nitrogen, 

 but of constant carbon dioxide content. The latter precaution removed 

 a second variable. The p0 2 was determined in the gas mixture and not 

 in the blood. Upon the latter, after equilibration, the percentage 

 saturation was determined by an indirect, standard gasometric pro- 

 cedure 14 ' 15 , the reliability of which for this purpose has come to be 

 seriously questioned 10 ' 16 . The classical oxygen dissociation curves 

 have been plotted from such data, and show the percentage of oxy- 

 haemoglobin, inferred to be synonymous with the percentage saturation, 

 against corresponding p0 2 (and at constant pC0 2 ). It has been 

 assumed that these curves represented what would have been obtained 

 if the determinations had been done upon blood ' equilibrated ' in vivo 

 rather than in vitro. And, owing to the then unavailable micro method 

 for the direct accurate determination of the blood p0 2 , the practice 

 originated of analyzing for percentage saturation and ' determining ' 

 the corresponding pO 2 by reading if off from the previously constructed 

 dissociation curves. As the curves were asymptotic at higher p0 2 

 values (Figure 4) it should have been obvious that, at least in this 

 region, the procedure was scarcely precise. 



This practice of indirectly obtaining the p0 2 has had an important 

 consequence upon physiological thought in this field. Gasometric 

 determinations of the degree of saturation (per cent of oxyhaemoglobin) 

 of the arterial blood of man at sea level yielded values as low as 93 per 

 cent, with a mean of 95 per cent 17 " 19 . On typical dissociation curves 20 



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