Oxygen isotope fractionation in healthy subjects and in patients with COPD.

We determined the oxygen isotope fractionation degree for oxygen utilized (delta(U)) in expired alveolar gas relative to inspired air in patients with chronic obstructive lung disease (COPD) and, for comparison, in two groups of healthy subjects, old and young. In addition, we determined Delta(rel)R(vent) and Delta(rel)R(tot). These determinants of delta(U) (=Delta(rel)R(tot)-Delta(rel)R(vent)) are related to the oxygen isotope fractionation which occurs in the first part of the O(2) pathway by ventilation of alveolar gas (Delta(rel)R(vent)) and by O(2) transport and utilization in the rest of the O(2) pathway from the alveolar space (Delta(rel)R(tot)). Mean delta(U) values for the three groups of subjects were close: 9.0, 9.0 and 9.9 per thousand, respectively, with no significant differences between groups. Mean Delta(rel)R(vent) for patients with COPD was substantially larger than for young, healthy subjects, 4.0 per thousand versus 0.94 per thousand, with P<10(-3). This result indicates that the contribution of intrapulmonary gas transport by diffusion to Delta(rel)R(vent) is larger for patients with COPD than for young, healthy subjects. Mean Delta(rel)R(tot) for patients with COPD was also larger than for young, healthy subjects, 13.0 per thousand versus 10.84 per thousand, but this difference was not significant (P=0.06). Further, Delta(rel)R(tot) was much larger than Delta(rel)R(vent) for all groups of subjects (P<10(-7)).

A discussion regarding the contribution of intrapulmonary gas mixing to O2 isotope fractionation by respiration using experimental data for 36Ar and 40Ar.

We determined the argon (Ar) isotope ratio in samples of expired alveolar gas gathered during Ar washout from residual gas relative to this ratio in samples of expired alveolar gas gathered just before the beginning of this washout in 13 young, healthy human subjects at rest. These data were determined for a limited number of breaths in early washout and were used to calculate the relative difference between the alveolar ventilations of (36)Ar and (40)Ar (Delta(rel)V (A)((36)Ar,(40)Ar)). Mean Delta(rel)V (A)((36)Ar,(40)Ar) amounted to 1.6 per thousand (S.D.=1.3 per thousand). This result was then used to discuss the contribution of intrapulmonary gas mixing by diffusion to oxygen isotope fractionation of alveolar gas by respiration. On the basis of our finding for Delta(rel)V (A)((36)Ar,(40)Ar) and further theoretical considerations we arrived at the conclusion that this contribution for subjects at rest is small (about 1 per thousand) and that this contribution is negative irrespective of the level of exercise.

The influence of training on oxygen isotope fractionation in healthy subjects.

We determined the oxygen isotope fractionation in expired alveolar gas relative to inspired air (delta(A-I)) in eight young, healthy subjects at rest and at five levels of exercise up to maximal workload both before and after a training period of about 4 weeks which increased maximum oxygen uptake by about 10%. The data for delta(A-I) were used to compute the relative difference (deltaU) between the resistances of 16O18O and 16O2 for oxygen transport from the alveolar space and utilization in the mitochondria. Prior to training, deltaU decreased from 15 per thousand at rest to 5 per thousand at the highest level of exercise and after training from 12 to 5 per thousand. The difference between the results for deltaU before and after training was significant for rest (P < or = 5) but not for exercise conditions. Accordingly, we conclude that for exercise conditions the non-fractionating oxygen transport by blood flow to and the fractionating oxygen transport by diffusion in the muscles have improved by training to more or less the same degree. The decrease in deltaU in rest after training suggests that oxygen transport by diffusion in other tissues also benefits from the effects of training.

Modeling of the expiratory flow pattern of spontaneously breathing cats.

A mathematical model was developed describing the entire expiratory flow pattern during spontaneous, tidal breathing in the absence of expiratory muscle activity. It provides estimates for the time constants of the respiratory system (tau RS(model)) and of the decay of continuing inspiratory muscle activity in early expiration (tau mus(model)). In ten anesthetized, tracheostomized cats flow, tracheal pressure and diaphragmatic EMG were measured during normal expirations and expirations with four different added resistances. No significant differences were found between tau RS(model) (0.21-0.49 sec) obtained by fitting the model to the flow data and tau RS obtained from the straight part of the expiratory flow-volume curve. tau mus(model) (0.050-0.052 sec) was comparable to similar time constants obtained from the integrated diaphragmatic EMG or from end-inspiratory, tracheal occlusion pressure. Fitted peak flow and time to peak tidal expiratory flow were not significantly different from those measured. In conclusion, for spontaneously breathing, anesthetized cats our model provides a close fit of the expiratory flow and parameter estimates were comparable with independently measured values.

The ratio of the alveolar ventilations of SF6 and He in patients with lung emphysema and in healthy subjects.

This study assess the possible impact of changes in the morphometry of acinar airways and air spaces on the efficacy of intrapulmonary gas mixing for sulphur hexafluoride (SF6) relative to that for helium (He). To that end the alveolar ventilations of He and SF6 were determined in patients with macroscopic lung emphysema and in healthy subjects. He-SF6 washout tests were performed in 17 patients (15 emphysema, 2 chronic bronchitis) and 21 healthy subjects. Using a three-compartment model, the data obtained were used to estimate the overall, effective, alveolar ventilations of SF6 and He, and their ratio VAASF6/VAHe. Mean VAASF6/VAHe (+/- S.D.) for patients (0.80 +/- 0.06) was significantly smaller (P < 0.001) than the value for the group of age-matched healthy subjects (0.90 +/- 0.05) which was non-significantly smaller than the result for the group of young, healthy subjects (0.93 +/- 0.03). In our patients, we also determined a score for emphysema using high resolution computed tomography, and this score correlated inversely with VAASF6/VAHe (r = -0.56, P = 0.018). We have interpreted our observations to mean that in patients with lung emphysema, the efficacy of intrapulmonary gas mixing for SF6 as compared with that for He reflected by VAASF6/VAHe is diminished due to increased diffusive path-lengths within the enlarged air spaces of their lungs which impair diffusive gas mixing for SF6 more than for He.

Collateral gas transport by diffusion across tissue in the healthy, human lung; effects on dead space.

The effects of collateral gas transport by diffusion across lung tissue on the Bohr and Fowler dead spaces were quantified for resting breathing conditions. The dead spaces (VD) of He, Xe and SF(6) were determined from expirograms obtained from the simultaneous washout of these test gases. The experiments were performed on seven healthy subjects. The contribution of collateral gas transport by diffusion on VD was obtained from the difference between VD(SF(6)) and VD(Xe). These two gases have comparable diffusion coefficients (D) in residual gas but in lung tissue D(Xe) is roughly 25 times larger than D(SF(6)) due to the higher solubility of Xe in aqueous tissues. The data showed that the reducing effect of collateral gas transport by diffusion on VD(Xe) amounts to about 2 ml for both the Bohr and the Fowler dead space. The smallness of this effect means that the alveolar ventilation for Xe hardly benefits from this additional mechanism of intrapulmonary gas mixing.