Diffusion limitation and limitation by chemical reactions during alveolar-capillary transfer of oxygen-labeled CO2

A major difficulty in the measurement of carbon dioxide diffusing capacity is the development of significant CO2 back pressure within the capillary. The use of oxygen-labeled CO2 limits this back pressure due to rapid dilution of the label into the water pool by isotopic exchange. We demonstrated the use of C16O18O to measure DCO2 (Schuster, 1985). A major question from that study is whether the isotope measures a true membrane diffusing capacity or is limited by back reaction. In this study we examine the diffusing capacity of doubly 18O-labeled carbon dioxide, C18O2, a species in which the kinetics of isotopic exchange in pulmonary blood is higher than that of C16O18O. Eighteen single breath experiments were performed on two resting male subjects whose CO2-transfer-kinetics was previously studied with C16O18O (Schuster, 1985). Following expiration to residual volume the subjects inspired a gas mixture containing 20% O2 and 1.5-2.6% C18O2. After holding their breath for 0.4-17 sec they exhaled into a tube and the end-expired gas was analysed by mass spectrometry. The time course of the C18O2 disappearance from alveolar gas showed a biexponential characteristic as that which had been measured with C16O18O, but C18O2 disappeared faster. The mean value of the diffusing capacity of C18O2 amounts to 1102 ml mmHg-1 X min-1. It is 228 +/- 163 ml mmHg-1 X min-1 greater than that of C16O18O. This significant difference suggests that: DC16O18O is limited in part by isotopic exchange reactions; the observed DC18O2 may be taken as a new lower limit for DMCO2, higher than values established from other techniques; the decarboxylation of bicarbonate in red cells is not a rate limiting step for CO2 exchange.