Tracer disequilibrium in CO₂ compartments during NaH¹⁴CO₃ infusion

The failure of labeled CO₂ to equilibrate between extracellular and intracellular CO₂ compartments may influence the accuracy of substrate oxidation measurements during infusion of carbon-labeled tracers because it may generate errors in estimate of fixation of labeled CO₂ derived from control experiments in which labeled bicarbonate is infused. In this study, normal volunteers received a 14-hour overnight primed continuous infusion of NaH¹⁴CO₃. Over the last 4 hours of the study, steady-state conditions were achieved in the specific activities (SAs) of expired ¹⁴CO₂ and plasma urea, which was used as a probe for hepatic intracellular CO₂ SA. Plasma urea SA was approximately 17% lower than expired CO₂ SA (46.4 ± 5.6 v 56.8 ± 3.9 disintegrations per minute · μmol^-1, P < .02). Fractional ¹⁴CO₂ recovery was 94.8% ± 0.8%; when corrected for failure to equilibrate with intracellular CO₂, fractional recovery was 89.5% ± 1.9%. These data indicate that compartmentalization of CO₂ may occur in humans. The duration of our experiments, required because of the long half-life of plasma urea, may have minimized the apparent magnitude of compartmentalization. Furthermore, it is possible that compartmentalization in extrahepatic tissues could be of either lesser or greater magnitude than that which we observed in liver. Whether this phenomenon contributes to incomplete recovery of ¹⁴CO₂ during NaH¹⁴CO₃ infusion cannot be determined from our results. Additional studies using different experimental approaches will be required to better measure CO₂ compartmentalization.