Current methods of forcing end-tidal P CO 2 (P ETCO 2 ) and P O 2 (P ETO 2 ) rely on breath-by-breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo-control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath-by-breath basis. In this paper, we introduce a low gas flow method to prospectively target and control P ETCO 2 and P ETO 2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change P ETCO 2 from control (40 mmHg for P ETCO 2 and 100 mmHg for P ETO 2 ) to two target P ETCO 2 values (45 and 50 mmHg) at iso-oxia (100 mmHg), P ETO 2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and P ETCO 2 with P ETO 2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, P ETCO 2 and P ETO 2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for P ETCO 2 was ± 1 mmHg, and for P ETO 2 was ± 4 mmHg. P ETCO 2 varied by ± 1 mmHg and P ETO 2 by ± 5.6 mmHg (S.D.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (± 7.6 l min −1 ). We conclude that targeted end-tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed-forward, low gas flow system.

Accurate measurements of arterial P CO 2 (P a,CO 2 ) currently require blood sampling because the end-tidal P CO 2 (P ET,CO 2 ) of the expired gas often does not accurately reflect the mean alveolar P CO 2 and P a,CO 2 . Differences between P ET,CO 2 and P a,CO 2 result from regional inhomogeneities in perfusion and gas exchange. We hypothesized that breathing via a sequential gas delivery circuit would reduce these inhomogeneities sufficiently to allow accurate prediction of P a,CO 2 from P ET,CO 2 . We tested this hypothesis in five healthy middle-aged men by comparing their P ET,CO 2 values with P a,CO 2 values at various combinations of P ET,CO 2 (between 35 and 50 mmHg), P O 2 (between 70 and 300 mmHg), and breathing frequencies (f ; between 6 and 24 breaths min −1 ). Once each individual was in a steady state, P a,CO 2 was collected in duplicate by consecutive blood samples to assess its repeatability. The difference between P ET,CO 2 and average P a,CO 2 was 0.5 ± 1.7 mmHg (P = 0.53; 95% CI −2.8, 3.8 mmHg) whereas the mean difference between the two measurements of P a,CO 2 was −0.1 ± 1.6 mmHg (95% CI −3.7, 2.6 mmHg). Repeated measures ANOVAs revealed no significant differences between P ET,CO 2 and P a,CO 2 over the ranges of P O 2 , f and target P ET,CO 2 . We conclude that when breathing via a sequential gas delivery circuit, P ET,CO 2 provides as accurate a measurement of P a,CO 2 as the actual analysis of arterial blood. Accurate measurement of arterial P CO 2 (P a,CO 2 ) is important for the clinical assessment of patients and, in physiological studies, for the assessment of control of breathing and cerebral blood flow. Currently, the reference standard for measuring P a,CO 2 is analysis of arterial blood via direct arterial puncture. This invasive approach has a number of disadvantages for both the subject (discomfort and potential arterial wall damage) and investigator (restricted mobility of the catheter insertion site, cost, time delay for blood analysis, and limited temporal resolution of changes in P a,CO 2 ). As a result, investigators have long sought a suitable non-invasive method to measure P a,CO 2 .Non-invasive methods of predicting P a,CO 2 from alveolar P CO 2 (P A,CO 2 ) consider the lung to be a tonometer in which CO 2 equilibrates between alveolar gas and capillary blood. In reality, however, the lung is not a single homogeneous time-invariant gas exchange compartment. Rather, P CO 2 varies in different regions of the lung as a result of differences in ventilation-to-perfusion matching (V A /Q ) throughout the lung and, in each lung region, throughout the respiratory cycle (Dubois et al. 1952;Lenfant, 1967). The contribution to the P a,CO 2 of blood passing each alveolus reflects the average P CO 2 in that alveolus during the respiratory cycle (Jones et al. 1979;Robbins et al. 1990). P a,CO 2 , then, reflects the timeand flow-weighted averages of all alveolar ventilatory fluctuations in allV A /Q regions throughout the lung, i.e. the mean P A,CO 2 (Lenfant, 1967). As a result, the r...

The BOLD reactivity to PETO(2) was much smaller than that to PETCO(2). However, BOLD reactivity can be significantly distorted by CO(2)-induced changes in PETO(2). We conclude that PETO(2) should be carefully controlled during studies that use BOLD reactivity as an indicator of CVR.