Hyperchylomicronemia, oxygen affinity and proton passage across the red cell membrane

Previously we have shown that HC alters significantly the affinity of hemoglobin for oxygen. This evidence stands in support of earlier investigations presented by Ditzel and Dyerburg (1977). Exposure to 6% chylomicra, slowly produced a decrease in the pO2 of human blood (37 degrees C, at in vivo pH) amounting to a 6.0 mm Hg leftward shift in the P-50. This increase in oxygen affinity may be due to the Bohr shift since exposure to HC produced an increase in intracellular pH by abolishing the proton gradient across the red cell membrane. We postulate that exposure to HC might physically modify the composition of the red cell membrane so that proton passage is permitted and the intracellular pH rises to approximate that of the extracellular pH. An oxidative phosphorylation uncoupling agent (CCCP), abolishes the proton gradient and produces an immediate decrease in the pO2 similar to that produced by HC. We explored the suggestion that proton passage might be facilitated by an increase in the membrane fluidity produced by a decrease in membrane cholesterol. However no decrease in red cell membrane cholesterol was found on exposure to 6% chylomicra. Although the molecular mechanism remains unclear, this event would dramatically reduce oxygen delivery to the myocardium and might prove to be an important factor in the incidence of myocardial hypoxia.