Endogenous carbon monoxide production in patients with hemolytic anemia.

It is desirable in many studies to be able to rapidly measure rates of erythrocyte and hemoglo-bin destruction. Labeling techniques have been utilized for this purpose but have the disadvantage of requiring several days' to weeks to obtain the desired data plus the hazards of radioactive isotopes. Estimations of hemoglobin turnover from measurements of fecal bile pigment or serum bili-rubin concentrations contain large sources of error (1). Studies in which bile pigment is collected via bile duct fistulas have been of value in animal experiments (2) but are-not usually possible in man, and subjects who have bile fistulas cannot be called normal. At the present time it appears that many in vivo investigations of red cell survival in patients with hemolytic disease are limited by the lack of a precise rapid method for detecting changes in the rate of red cell destruction. It has been shown previously (3-9) that CO is an in vivo catabolic by-product of hemoglobin and that it probably originates from the heme a-methine bridge carbon atom. Data obtained in experiments where CO production was measured after intravenous injections of suspensions of damaged erythrocytes or solutions of hemoglobin have indicated that the molar yield of CO produced to heme catabolized is approximately unity in normal man (6) and anesthetized dogs (9). Apparently, therefore, the measurement of CO production is useful in studying hemoglobin and red cell turnover and can be utilized in studies of patients with increased erythrocyte destruction. The quantita-tion of erythrocyte and hemoglobin 'catabolism from CO production measurements has the advantages that it is rapidly accomplished, does not require isotopes, and can be repeated. Early workers (4, 10) attempted to estimate red cell survival with measurements of the venous blood carboxyhemoglobin per cent saturation ([COHb]) in patients with hemolytic anemia; this approach seems inadequate in view of the uncertainties of the relationship of [COHbJ to the actual rate of CO production in these patients (11). The development of a method of estimating the rate of CO production (Nrco) based on 'the measurement of the rate of increase in CO body stores under conditions where CO excretion from the body is prevented by having the subject re-breathe in a closed system has apparently circumvented this difficulty (5). In the present report we describe a modification of the rebreathing system that has allowed us to measure Vco in seriously ill and debilitated patients. With this system Vco …