Demonstration and quantification of the redistribution and oxidation of carbon monoxide in the human body by tracer analysis

Numerous studies have confirmed the role of endogenous carbon monoxide (CO) gas as a signal transmitter. However, CO is considered an intracellular transmitter, as no studies have demonstrated the redistribution of CO from the blood to tissue cells. Tracer analyses of 13CO2 production following 13CO gas inhalation demonstrated that CO is oxidized to carbon dioxide (CO2) in the body and that CO oxidation does not occur in the circulation. However, these results could not clearly demonstrate the redistribution of CO, because oxidation may have occurred in the airway epithelium. The objective of this study, therefore, was to definitively demonstrate and quantify the redistribution and oxidation of CO using time-course analyses of CO and 13CO2 production following 13CO-hemoglobin infusion. The subject was infused with 0.45 L of 13CO-saturated autologous blood. Exhaled gas was collected intermittently for 36 hours for measurement of minute volumes of CO/CO2 exhalation and determination of the 13CO2/12CO2 ratio. 13CO2 production significantly increased from 3 to 28 hours, peaking at 8 hours. Of the infused CO, 81% was exhaled as CO and 2.6% as 13CO2. Identical time courses of 13CO2 production following 13CO-hemoglobin infusion and 13CO inhalation refute the hypothesis that CO is oxidized in the airway epithelium and clearly demonstrate the redistribution of CO from the blood to the tissues. Quantitative analyses have revealed that 19% of CO in the circulating blood is redistributed to tissue cells, whereas 2.6% is oxidized there. Overall, these results suggest that CO functions as a systemic signal transmitter.