In vivo red cell glycolytic control and DPG-ATP levels.

Abstract

Much of clinical medicine involves a struggle against hypoxic diseases (such as heart disease, pulmonary disease, and anemia), all of which owe their morbidity and mortality ultimately to inadequate tissue oxygenation. Because of the quantitative significance of these kinds of diseases in health today, it is particularly important to try to understand and exploit the possible compensatory mechanisms for inadequate tissue oxygenation. FIGURE 1 puts the role of the red cell in perspective with other factors influencing tissue oxygenation. As the figure indicates, the factors that influence tissue oxygenation can be considered under four categories : cardiac output, pulmonary oxygen exchange, red cell oxygen transport, and lastly, hematological parameters, that is, red cell mass and amount of hemoglobin per red cell. Of course, an abnormality in any one of the four oxygen transport factors can be compensated somewhat by alterations in the other three factors. For instance, anemia leads to an increase in cardiac output and hyperventilation as well as to changes in red cell oxygen transport. Our emphasis in this paper, however, centers on those changes within the individual red cell that may improve its oxygen delivery during each transit through the tissue. Potentially, the most important change in this regard is a decrease in the oxygen affinity of the red cell (a shift to the right of the oxygen dissociation curve). A question of importance that has not yet been answered is whether or not oxygen affinity within the ranges seen normally and pathologically in various mammalian species really influences function. Theoretically, it can be shown in man that a 3 mm right shift in the oxygen dissociation curve, as might be produced by a 25% increase in DPG,t has a potential for 22% greater oxygen transport if cardiac output, ventilation, and hemoglobin levels remain the same.’ This theoretical benefit is based upon essentially a resting situation in which blood with a normal oxygen affinity returns to the lungs with approximately 70% of its oxygen remaining, whereas with a decrease in oxygen affinity the blood returns more deoxygenated. With stress such as exercise or in certain organs such as the heart, desaturation is more complete and the theoretical benefit of decreased oxygen affinity is relatively less. The effect of changes in oxygen affinity can also be examined in terms of the hypothetical drop in tissue