Methemoglobin formation and red cell metabolism in guinea pigs during chronic hypercapnia.

=> 7' 7 ,72 Recent studies of chronic hypercapnia in guinea pigs and rats demonstrated a biphasic shift in the blood oxygen dissociation curve, a diminution of heme-heme interaction and a significant decrease in the oxygen capacity of blood which was not due to decreased hemoglobin content. The latter finding suggested production of non-functional hemoglobin during hypercapnia. We measured the concentration of oxidized (met) hemoglobin and found an increase from control values of 2. 69% to 8. 73% at 1 day, 6.4% at 3 days and 6.2% at 7 days of 15% CO2 exposure. The values are correlated with the biphasic changes in oxygen affinity (P50) and heme-heme interaction (n) of blood oxygen dissociation curves during hypercapnia. Hemoglobin oxidation is enhanced by low pH, and inhibition of red cell catalase by CO2 resulting in increased oxidation by H2O2 may also be partially responsible for methemoglobin formation. The persistence of methemoglobin results from inhibition by low pH of the enzyme systems which convert methemoglobin to hemoglobin.